1
Q
Hormone was derived from the Greek word meaning what?
A
To arouse or excite
2
Q
What are hormones important for?
A
Reproduction, growth and development, homeostasis, and energy production, utilization, and storage
3
Q
What is the difference between nervous system and endocrine system reaction time?
A
Nervous system reacts much faster and is suited to the more rapid and transient activities, while the endocrine system is slower and regulates longer-lasting effects
4
Q
Define hormone
A
Chemical messengers produced by one cell to regulate activity of another cell, and delivered by means of endocrine, neuroendocrine, paracrine, autocrine, neurocrine, or pheromonal route
5
Q
Describe the endocrine system
A
The hormone is released by secretory cells into the circulation and is transported to the target cell by blood vessels
6
Q
Provide an example of a hormone that uses the endocrine route
A
Gonadotropin (pituitary to gonads), TSH (pituitary to thyroid), etc
7
Q
Describe the neuroendocrine system
A
The hormone is released by nerve cells into the circulation and is transported to the target cells by blood vessels (requires neuronal stimulation)
8
Q
Describe the paracrine system
A
The hormone is released interstitially and diffuses to its target cell through extracellular fluid
9
Q
Provide an example of a hormone that uses the neuroendocrine route
A
Vasopressin is secreted by hypothalamic neurons and stored in the pituitary, then released via neuronal signal to the kidneys and smooth muscle tissue
10
Q
Provide an example of a hormone that uses the paracrine route
A
Growth factors like epidermal growth factor 1 (EGF-1)
11
Q
Describe the autocrine system
A
The target of the secreted hormone is the same cell that released it
12
Q
Provide an example of a hormone that uses the autocrine route
A
Prostaglandins and some GFs
13
Q
Describe the neurocrine system
A
Neurons secrete the hormone in the immediate vicinity of the target cell (synaptic cleft)
14
Q
Provide an example of a hormone that uses the neurocrine route
A
Neurotransmitters like norepinephrine and dopamine
15
Q
True/False? Most hormones are restricted to one or two routes
A
False. Most hormones do not act within a singular route and may produce a variety of cellular responses depending on the target cell
16
Q
Describe how pheromones work
A
The hormone is released into the environment to induce a biological response in another animal. Species-specific, also sometimes called exocrine
17
Q
What are the types of hormones?
A
- peptides and proteins
- steroids
- amino acids and amino acid derivatives
- eicosanoids
18
Q
Describe protein-based hormones
A
- names usually end in “-in”
- can range from a few AA to many AA
- adopt a conformation that has high affinity for its receptors
- usually have cell-surface receptors (too large to go into the cell)
19
Q
Describe steroid hormones
A
- derived from a cholesterol precursor
- names usually end in “-ogen” or “-oid”
- can pass through the membrane to bind to intracellular receptors
20
Q
Examples of protein hormones
A
- insulin
- GH
- TSHRH
- GRH
- somatostatin
21
Q
Examples of steroid hormones
A
- androgens
- estrogens
- progestogens
- corticosteroids
22
Q
Describe amino acid hormones
A
- names usually end in “-ine”
23
Q
Examples of amino acid hormones
A
- thyroxine
- iodothyronine
- epinephrine
- norepinephrine
24
Q
Describe eicosanoids
A
- fat-soluble
- associated with cell membranes
- can end in “-in” (confusing with protein hormones)
25
Examples of eicosanoids
- prostaglandins
- prostacyclins
26
Hormone receptors are usually what kind of molecule group?
Glycoproteins
27
Describe hormone specificity
Hormones are very specific to their receptors and this specificity is achieved via the Lock and Key mechanism where activation of the receptor requires the ligand to be the correct shape (binding) and charge (activation)
28
Agonistic hormones:
Stimulate their pathway
29
Antagonistic hormones:
Inhibit their pathway
30
What are the two functions of receptors?
Recognition (specific binding) and transduction of signal
31
Competitive antagonistic hormones:
Bind the receptor to prevent the agonists from binding
32
Examples of agonistic hormones:
- testosterone (androgen)
- estradiol (estrogen)
- progesterone (progestogen)
33
Examples of antagonistic hormones:
- cyproterone acetate (anti-androgen)
- tamoxifen (anti-estrogen)
- RU486 (anti-progestogen)
34
The hormone-receptor interaction is (rapid/slow) and (irreversible/reversible)
Rapid; reversible
35
What constant dictates the rate of association between hormone and receptor? Units?
Association rate constant (K+1). /(M*s)
36
What constant dictates the rate of dissociation between hormone and receptor? Units?
Dissociation rate constant (K-1). /s
37
When is equilibrium reached between hormone-receptor interactions?
Association and dissociation occur at the same rate (K+1 = K-1)
38
What is the Equilibrium Association Constant? Formula and units?
Ka is how strong the hormone binds to its receptor (affinity), where the higher the Ka, the longer the interaction between H and R; (K+1)/(K-1), units: /M
39
What is the Equilibrium Dissociation Constant? Formula and units?
The concentration/potency of the hormone at half the maximum biological response, where the higher the Kd, the more hormone is needed to reach 100% response; 1/Ka, units: M
40
What is ED50?
Analogous to Kd. The effective dose of a hormone giving half maximal biological response. It is a measure of potency and is a function of receptor affinity
41
What does it mean about receptor occupation when biological response for a hormone is at 100%?
All receptors occupied, equilibrium reached
42
Why can biological response to a hormone never be 0%?
Because the organism would have to be dead
43
True/False? Receptor binding affinity is subject to hormone concentration
False. It is subject to chemical changes that may reduce or increase binding affinity. Hormone concentration does not change binding affinity
44
What is receptor capacity?
The number of receptors available for binding to their ligands
45
Upregulation of biological response to a hormone is caused by what?
Increased receptor synthesis, availability, and affinity
46
Downregulation of biological response to a hormone is caused by what?
Decreased receptor synthesis, availability, and affinity
47
A change in the receptor capacity effects what? What happens to the responsiveness curve?
Maximum responsiveness, where an increase in capacity increases the response and vice versa; maximum of response is either increased or decreased, but Kd remains the same
48
A change in receptor affinity effects what? What happens to the responsiveness curve?
Kd or ED50 (analogous), where an increase in affinity decreases Kd and vice versa; If Kd increases, then the curve is shifted to the right (higher [ligand] needed for maximum response) and vice versa, but maximum response stays the same
49
True/False? Receptor capacity and affinity are not mutually exclusive, so both can happen at once
True
50
What are the two locations hormone receptors can be located?
Intracellular (cytosol or nucleus) and plasma membrane
51
What is an intracellular receptor? Provide some examples of hormones that would use these receptors
Receptor is located within the cytosol or nucleus; steroid hormones or iodothyronines (they can cross the membrane)
52
What is a plasma membrane receptor? Provide some examples of hormones that would use these receptors
Recognition sites lie at the cell surface; peptide, protein, and catecholamine hormones (cannot cross the membrane)
53
True/False? Plasma membrane receptors can be found intracellularly
True. May be located on organelle membranes if the hormones are autocrine
54
Why do receptors lose function at low temperatures?
They require the membrane to be fluid so they can move laterally within the membrane. If temperatures are too low, membrane fluidity is decreased so receptors are unable to dimerize/bind activating proteins
55
What are the two ways a signal may be transduced in a receptor/hormone interaction
- specific binding
- transduction of signal coupled to intracellular effectors system
56
How do hormones that have intracellular receptors get to their receptors from the bloodstream?
Steroids and thyroid hormones bind specific proteins in circulation, then dissociate and enter the cell membrane through diffusion (steroids) or facilitated transport (thyroid hormones) to bind to their receptors
57
Why do steroids and thyroid hormones require binding proteins?
The binding proteins increase the half-life of extracellular hormones
58
Intracellular receptors, once bound to their ligand, may enter the nucleus and bind to the _____________ as a ______________ to facilitate gene transcription
Hormone response element (HRE); transcription factor (TF)
59
What are the three domains needed by intracellular receptors? What is another name for these receptors that describes their action?
Binding domains: hormone, DNA, activation;
ligand-activated transcription factors
60
List the steps from circulation to transcription activated by steroid and thyroid hormones
1. Hormone binds binding protein in circulation
2. Hormone dissociates from binding protein and enters the cell (diffusion for steroid, facilitated transport for thyroid hormones)
3. Hormone binds specifically to receptor
4. HR complex binds HRE on DNA
5. Promoter stimulated and transcription activated
61
True/False? Steroid and thyroid hormones act through membrane-associated receptors and intracellular receptors
True. Evidence suggests they can act through both mechanisms, however, for MC questions, pick intracellular. For written questions, it is allowable to say both
62
What are the two pathways a protein, peptide, or catecholamine can activate its receptor?
- a process intrinsic to the receptor (tyrosine kinases or ion channels)
- interaction of the receptor with other membrane proteins (GPCR)
63
What are the two classes of membrane receptors?
1. receptor and effector site are contained in a single molecule (effector may be an enzyme like RTK or an ion channel like the ligand-gated Na+ channel)
2. Receptor and effector site are two separate molecules coupled by a third molecule, G-protein (effector is an enzyme like Adenylyle Cyclase or PIPC, or effector is an ion channel like K+ or Ca2+ channels)
64
What kind of receptor is the receptor for TSH?
Membrane GPCR that activates Adenylyle Cyclase activity
65
Somatostatin opens what channel?
K+ channel
66
Epinephrine opens what channel?
Ca2+
67
RTKs bind what ligands?
EGF-1 and insulin
68
What are the three domains of an RTK?
- single protein chain with extracellular ligand-binding domain
- transmembrane domain consisting of leucines and an alpha-helix
- intracellular domain with a tyrosine kinase catalytic domain
69
Describe the structure of the insulin and IGF-1 RTKs
- one alpha subunit that binds ligand
- one beta subunit that has extracellular, transmembrane, and intracellular domains
Alpha and beta are covalently linked extracellularly, RTKs dimerize once bound to ligand
70
What is the activity conducted by the intracellular domain of an RTK?
Autophosphorylation or transphosphorylation with the dimer
71
What is the activation pathway for RTKs?
1. Hormone binds extracellular domain
2. Receptor dimerization
3. Activation of RTK in intracellular domain
4. Autophosphorylation/transphosphorylation of the receptor
5. Activation of MAPK (MAP kinase)
6. Phosphorylation of transcription factors
7. Biological response
72
True/False? Like steroid and thyroid hormones, RTKs transcription factors need to be activated by hormone binding
False. They require phosphorylation by kinases as the hormones that activate the pathway cannot cross the membrane
73
Provide an example of an ion channel that has an effector site
The nicotinic acetylcholine receptor (nACH-R) is a Na+ channel that requires ACh to bind to both of its alpha-subunits. Upon ACh binding, the channel opens, which allows Na+ ions to flow inside the cell (effector neurons), causing an action potential
74
How does Black Mamba venom work?
It has a higher affinity for the nACH-R than ACh, so it acts as a competitive antagonist and irreversibly binds. This stops action potentials from happening so the victim is paralyzed
75
How many subunits does the nACH-R Na channel have?
2 alpha, beta, gamma, and delta (5 subunits)
76
What are the four separate components required to generate a signal in a GPCR
- ligand
- receptor
- enzyme
- coupling protein (G-protein)
77
What are the enzymes commonly associated with GPCRs?
Adenylate/Adenylyle cyclase and phosphoinositide-specific phospholipase Cβ (PIPL-Cβ)
78
What are the different types of G-proteins?
Gs, Gi, and Gq/G11
79
Gs function
Stimulates adenylate cyclase
80
Gi function
Inhibits adenylate cyclase and activates phosphodiesterase
81
Gq/G11 function
Stimulates phosphatidylinositol-phospholipase Cβ (PI-PLCβ)
82
G-proteins consist of which subunits? How does the composition change when the hormone binds the receptor?
Alpha, beta, and gamma; they all dissociate from the receptor, but beta and gamma stay linked, while alpha is alone
83
Describe the adenylate cyclase activation pathway
1. Hormone binds GPCR
2. G-proteins (plus GDP-bound Gα) bind receptor on intracellular side
3. GDP into GTP triggers conformation change in α subunit that causes it to dissociate from beta, gamma subunits and receptor
4. *Gαs-GTP associates with adenylate cyclase (*C.αs)
5. *C.αs converts ATP to cyclic AMP (cAMP)
6. Activation of cAMP-dependent protein kinase A (PKA) by release of catalytic units of PKA from regulatory units (cAMP causes a conformation change upon binding)
7. Phosphorylation of Ser and Thr residues on target proteins (transcription factors)
8. Biological response
9. *Gαs-GTP hydrolyzed to Gαs-GDP to stop the response
84
How can adenylate cyclase be turned on for a longer period of time?
By inhibiting GTPase activity, which stops *Gαs-GTP hydrolysis into Gαs-GDP
85
How is PKA of the adenylate cyclase pathway turned off?
A phosphodiesterase hydrolyzes the phosphodiester bond on cAMP, turning it into AMP so it can no longer activate PKA
86
What are phosphodiesterases (PDEs) inhibited by? What does inhibition cause?
Methylxanthines (theophylline, caffeine, and aminophylline; causes a prolonged existence of cAMP and activated PKA, which cause jitters
87
Are PDEs exclusive to cAMP?
No, they also hydrolyze cGMP
88
Provide an example of PDE activity using cGMP. Also describe inhibition of PDE
PDE5 hydrolyzes cGMP in smooth muscle, causing smooth muscle relaxation. Reversible inhibition by sildenafil citrate blocks cGMP hydrolysis, leading to smooth muscle contraction and penile erection
89
Opioids bind to what kind of receptor? Which protein is the inhibitor?
GPCR's coupled to Gi proteins that, when turned on (*Gαi-GTP), turn off the active enzyme that converts ATP to cAMP (adenylate cyclase); Gαi
90
How do most calcium-mobilizing hormones elicit a cellular response?
They activate phosphatidylinositol (PI) turnover by a Gq-dependent mechanism
91
Describe the pathway mediated by Gq
1. Gq activates phosphatidylinositol-phospholipase Cβ (PI-PLCβ) with *Gαq-GTP
2. PI-PLCβ converts phosphatidylinositol 4,5-biphosphate (PIP2) into diacylglycerol and inositol triphosphate (IP3)
3. Diacylglycerol activates PKC while IP3 binds a Ca2+ channel on the ER, which releases Ca2+ into the cytoplasm
92
Where are diacylglycerol and inositol triphosphate located?
Intracellularly, with diacylglycerol in the membrane and inositol triphosphate in the cytosol
93
What is the significance of IP3's role as a Ca2+ channel opener?
When it binds the channel on the ER, the cytosolic [Ca2+] increases dramatically from 0. This is important for the stimulation of PKC (also stimulated by diacylglycerol), which elicits the phosphorylation of Ser and Thr residues on TF's, causing a biological response. The increase in [Ca2+] elicits other cellular responses by itself
94
True/False? PKC is highly specific
False. It activates pretty much any Ser or Thr containing protein that it comes along
95
What are the roles of intracellular Ca2+? Name 3
Increased Ca2+ content modified activity of cytoplasmic and mitochondrial enzymes such as:
- adenylate cyclase
- phosphodiesterase
- phospholipases
- calcium pumps
- microtubule disassembly
- membrane phosphorylation
- neurotransmitter release
- Ca2+-depenedent protein kinase I, II
- guanylate cyclase
- phosphorylase kinase
- myosin light-chain kinase
96
True/False? Gβ and Gγ play various roles when dissociated from Gα
False. Their role is mainly regulating ion channels, but is fairly useless otherwise
97
The phospholipase A2 pathway is important for the synthesis of what? Describe this pathway
Eicosanoids (prostaglandins, thromboxane A2, prostacyclin, leukotrienes)
1. Ligand binds receptor and activates phospholipase A2, which converts phospholipids into arachidonic acid
2. a) Cyclooxygenase Type-II (COX-II) converts arachidonic acid into prostaglandins, thromboxane A2, and prostacyclin
2. b) Lipoxygenase converts arachidonic acid to leukotrienes
98
Another word for pituitary
Hypophysis
99
What are the main jobs of the hypophyseal hormones?
- control of secretion
- peripheral actions
100
What are the main functions hypophyseal hormones control?
- uterine contractility
- milk production and secretion
- water balance
- blood pressure
- reproduction
- growth
- metabolism
- osmoregulation
101
How is the pituitary regulated?
Regulated by hypothalamic hormones (neurohormones)
102
What are the hypothalamic nuclei?
- supraoptic
- paraventricular
- preoptic
103
What is the embryonic progenitor of the anterior pituitary? What cells is it derived from?
Dorsal out/upgrowth of the buccal cavity; derived from epithelial cells (non-neuronal)
104
What is the embryonic progenitor of the posterior pituitary? What cells is it derived from?
Downgrowth of the brain; neuronal cells
105
What is the intermediate lobe?
A region between the anterior and posterior pituitary associated with the anterior pituitary. Not present in adult humans
106
What is another word for the anterior pituitary?
Adenohypophysis
107
If the intermediate lobe is not present in an animal's pituitary, where are the hormones it usually secretes, secreted instead?
Adenohypophysis
108
What are the divisions of the adenohypophysis?
Pars tuberalis (tuberal lobe), Pars intermedia (intermediate lobe), Pars distalis (anterior lobe)
109
What is another word for the posterior pituitary?
Neurohypophysis
110
What are the divisions of the neurohypophysis?
Infundibulum (neural lobe) and Pars nervosa (neural lobe/posterior pituitary)
111
Describe the synthesis and release of neurohypophyseal hormones
Hormones are synthesized in neurosecretory neurons in the hypothalamus and are released at a junction within the posterior pituitary, where they are stored an eventually released into the bloodstream
112
Neurohypophyseal hormones are an example of what hormone distribution pathway?
Neuroendocrine (axon terminals are located right outside of the blood vessel that would distribute the hormone)
113
Describe the synthesis and release of adenohypophyseal hormones
Stimulatory hormones are synthesized in neurosecretory neurons in the hypothalamus and secreted into the **Median eminence**. Hormones are then picked up by the **hypothalamic-hypophyseal portal system** and transported to the anterior pituitary, which stimulates it to synthesize the adenohypophyseal hormones, which are stored and released by the adenohypophysis.
114
Adenohypophyseal hormones are an example of what hormone distribution pathway?
Neuroendocrine
115
Which neurosecretory cells between the hypothalamus and the adenohypophysis vs. neurohypophysis would you expect to have longer axons?
Neurosecretory cells between the hypothalamus and neurohypophysis would have longer axons because they must stretch from the hypothalamus all the way to the pituitary, while the adenohypophysis has the hypophyseal portal stretching up into the hypothalamus
116
Where are neurohypophyseal hormones synthesized and released? Adenohypophyseal hormones?
Neurohypophyseal: synthesized in hypothalamus, released in neurohypophysis
Adenohypophyseal: synthesized and released in adenohypophysis
117
What are the hormones of the posterior pituitary? What are some common features they share?
Vasopressin (ADH, **AVP**) and oxytocin; both 9 amino acids long and both have a disulfide bond
118
True/False? While vasopressin and oxytocin have similar structures, their primary structure varies significantly
False. They are very similar in both regards and only differ by 2 amino acids (oxytocin has isoleucine and leucine, while vasopressin has phenylalanine and arginine)
119
Why is human vasopressin sometimes called AVP?
Stands for Arginine VasoPressin, which is what is found in humans. It has an Arg residue at position 8 of its sequence
120
True/False? Vasopressin and oxytocin are not the only neurohypophyseal hormones, and the others have different structures. The one thing they have in common is that they are all 9 amino acids long
True. All neurohypophyseal hormones are 9 amino acids long, even though they structurally vary
121
Where are vasopressin and oxytocin synthesized?
Hypothalamic neurons of the supraoptic and paraventricular nuclei
122
True/False? Both supraoptic and paraventricular neurons produce both vasopressin and oxytocin
True
123
What are the roles of the V1 and V2 AVP receptors? What are the key functions of AVP?
V1: mediate vascular smooth muscle contraction (increases blood pressure BP)
V2: produce renal action (water retention)
AVP increases BP by increasing vascular contraction and water retention (also facilitates memory consolidation)
124
Describe the effect of AVP on blood pressure
1. Baroreceptors sense a drop in blood pressure and stimulate AVP secretion
2. AVP causes water uptake (V2) and constriction of arterioles (V1)
3. Increase in blood pressure
125
Describe the effect of AVP on osmolality
1. Osmoreceptors sense an increase in blood osmolality and stimulate AVP secretion
2. AVP causes water retention and Na+ secretion (V2)
3. Urine increases in concentration and decreases in volume
126
How sensitive is the AVP response to plasma osmolality? Why?
Very sensitive (1% change activates AVP release) because a change in blood tonicity will damage blood cells and potentially harm the host
127
What is the relationship between AVP, blood pressure, and urine and plasma osmolality?
As [AVP] increases, so too do blood pressure and urine osmolality (when AVP is high, so are BP and osmo)
128
The release of AVP is stimulated by:
- increase in ECF osmolality
- decrease in blood volume
- decrease in blood pressure
- increase in Na+ in cerebrospinal fluid
- pain
- stress
- increase in temperature
- nicotine
- opiates
- barbiturates
129
AVP release is inhibited by:
- decrease in temperature
- ethanol (alcohol makes you pee more)
130
Why does alcohol make you pee more?
Alcohol inhibits AVP, so water is not retained as much as it otherwise would be, which means it ends up in the urine
131
What is the function of oxytocin? How is its release stimulated?
It stimulates milk ejection by contracting the myoepithelial cells in the mammary gland, also has a major role in childbirth where it causes contractions in the myometrium; stimulated by suckling of the breast and pressure on the cervix, respectively
132
True/False? Oxytocin naturally induces labour
False. It facilitates childbirth but does not naturally induce it, although it may induce pregnancy if medically administered
133
What kind of feedback loop does oxytocin have on its systems?
Positive feedback
134
What will happen to an expecting mother if she lacks adequate amounts of oxytocin?
She will have to deliver the baby via c-section and will not be able to breastfeed
135
True/False? The hypothalamus produces both inhibitory and excitatory hormones to inhibit/excite the release of adenohypophyseal hormones
True
136
True/False? Hormones released by the adenohypophysis can have both positive and negative feedback on the pituitary
True, however, it is important to note that the feedback also goes to the hypothalamus
137
What are the cell types located within the adenohypophysis?
- gonadotropes
- lactotropes
- somatotropes
- corticotropes
- thyrotropes
138
What hormone do lactotropes secrete?
Prolactin
139
What hormones do gonadotropes secrete?
Gonadotropins (LH and FSH)
140
What hormone do somatotropes secrete?
GH
141
What hormone do corticotropes secrete?
ACTH
142
What hormone do thyrotropes secrete?
TSH
143
How many families do the adenohypophyseal hormones fit into? What are the families and where are they located?
3 families; Family I (pars distalis), Family II (pars distalis), and Family III (intermediate lobe, if the organism has one. Otherwise, pars distalis)
144
GH and prolactin are part of which family of adenohypophyseal hormones? Where are they produced and secreted?
Family I; pars distalis in somatotropes and lactotropes
145
Glycoprotein hormones (like gonadotropins and TSH) are part of which family of adenohypophyseal hormones? Where are they produced and secreted?
Family II; pars distalis in gonadotropes and thyrotropes
146
Pro-opiomelanocortin (POMC)-derived hormones are part of which family of adenohypophyseal hormones? Where are they produced and secreted?
Family III: pars intermedia or pars distalis in melanotropes and corticotropes
147
What are the hormones of the adenohypophysis?
- LH and FSH
- prolactin
- GH
- ACTH
- α- and -MSH
- TSH
148
What hormone do melanotropes secrete?
Melanocyte-stimulating hormones (α- and β-MSH
149
Describe the features of Family I hormones
GH and prolactin (PRL) consist of approx. 200 amino acids as a single chain. They are synthesized by cleaving a large precursor protein at specific sites
150
Describe the features of Family II hormones
TSH, FSH, LH, and chorionic gonadotropin consist of α and β subunits, where the alpha subunit is the same for every glycoprotein hormone and the beta is unique for each (confer a functional property)
151
Where is chorionic gonadotropin synthesized? How does it differ from other glycoprotein hormones?
Produced in the chorion, so unlike the other glycoprotein (family II) hormones, it is not produced in the adenohypophysis
152
Glycoprotein hormones are (homodimers/heterodimers). What function does each subunit serve?
Heterodimers; the alpha subunit activates the beta subunit once associated, and the beta subunit confers a special functional property
153
Describe the features of Family III hormones
ACTH and MSH are derived from pro-opiomelanocortin (expressed in corticotropes and melanotropes), which is then cleaved by an enzyme unique to the cell type, resulting in the specific hormone for that cell type. These enzymes are in the prohormone convertase family
154
Where are ACTH and MSH produced?
ACTH is produced in the pars distalis and MSH (alpha and beta) are produced in the pars intermedia
155
Adult humans, birds, and marine mammals lack a pars intermedia. What does this mean for their ACTH and MSH production?
ACTH is produced regardless, because its produced in the pars distalis. α- and β-MSH are produced in the pars intermedia normally, but are produced in the pars distalis in these animals
156
What is the function of α-MSH?
α-MSH acts on melanocytes and stimulates dispersion of melanin granules within these cells, resulting in the darkening of the skin
157
In regards to the pituitary, how would a chameleon's brain differ from an adult human's?
A chameleon would rely more heavily on α-MSH for camouflage, so their pars intermedia would be larger
158
What are the factors effecting the release of prolactin from the adenohypophysis?
Dopamine: strong inhibitor
Cholecystokinin (CCK): weak stimulator
159
True/False? Prolactin is a hormone with a diverse range of functions. Explain why or why not
True. Has functions in reproduction, osmoregulation, growth, and development, although these effects are species-specific
160
Prolactin was believed to be the precursor of which hormone?
GH
161
What is unique about prolactin as an adenohypophyseal hormone?
It lacks a hypothalamic stimulatory hormone for release
162
What are the reproductive actions of prolactin in males?
It increases and maintains LH receptors in the testes (sustains testosterone level). Also increases sperm motility, helping with fertility
163
What are the reproductive actions of prolactin in females?
- stimulates lactation by stimulating the synthesis of casein (milk protein)
- increases progesterone synthesis
- stimulates the migration of IgA lymphoblasts to the mammary gland for baby passive immunity
- osmoregulation of embryonic fluid
- high levels during lactation reduce gonadotropin production, lower sex drive
164
What is placental lactogen?
A prolactin-like hormone produced by the placenta during pregnancy
165
What is another name for growth hormone? What does this name mean?
Somatotropin; growth/stimulation of somites (muscles)
166
What is the main action of GH? How does it exert this action?
Stimulation of somatic growth (skeletal and soft tissues); GH exerts both directly at the target cell or indirectly through production of growth factors like IGF-I and IGF-II
167
Which factors stimulate GH release?
GHRH (from the hypothalamus), hypoglycemia, and high protein meals
168
What factors inhibit GH release?
Somatostatin, IGF-I (negative feedback), and fatty acids
169
What are the secondary actions of GH?
Lipolysis and glucose uptake/mobilization
170
What are the direct actions of GH?
Increased cortisol production, which causes lipolysis in fat and increased blood sugar levels through decreasing glucose oxidation and suppression of muscular glucose uptake (anti-insulin)
171
What are the indirect actions of GH?
Stimulates IGF proteins, which mediate the production of thyroid hormones. Thyroid hormones increase skeletal growth via chondrogenesis and ossification and tissue growth through cellular differentiation and augmentation of trophic hormone actions
172
Describe how growth halts after puberty
Once GH is no longer produced, chondrogenesis at the epiphysis stops, at which point the cartilage fuses and completely ossifies
173
How do fatty acids inhibit GH?
A high fat content calls for insulin, which is inhibitory to GH. This causes stunted growth and obesity
174
Why must people with dwarfism get GH replacement therapy before puberty ends?
The epiphysis fuses at the end of puberty, at which point skeletal growth is no longer feasible
175
How does dwarfism occur?
GH deficiency early in life
176
What is the difference between Laron syndrome and dwarfism?
Laron syndrome results from GH receptor deficiency, while dwarfism results from GH deficiency
177
What is Laron syndrome and how may it be treated?
GH receptor deficiency, which can be treated with recombinant human IGF-I before puberty. Hormone therapy won't work because they don't have the receptors required
178
What is gigantism and how is it presented?
Excess GH occurs before epiphysis fusion, disproportionately long arms and legs
179
What is acromegaly and how is it presented?
Excess GH post epiphysis fusion, enlargement of the skull and facial bones, jaw, hands, feet, soft tissues, and organs
180
How may excess GH disorders be treated?
Somatostatin analogs or removal of pituitary
181
The removal of the pituitary vs. low thyroid levels on growth. What does this mean?
Removal of pituitary: no growth (GH is gone)
Low thyroid function: abnormal growth and development, but still some growth
GH and thyroid hormones work together for normal growth functions, but the system is completely dependent on GH and partially dependent on thyroid hormones
182
How may acquired hypothyroidism be treated?
Thyroid hormone treatment before puberty ends
183
Where are the thyroid glands located in humans? How do the glands differ between clades?
Located around the esophagus; fish have some scattered thyroid follicles, vary in shape, size, and lobe structure but synthesize hormones the same way
184
How may a thyroid gland be described?
A bag full of oranges
185
Describe the structure of the thyroid gland
Many follicles arranged together, which are lined with follicular cells. They surround a sac of fluid called colloid where thyroid hormones are stored
186
Describe what functions thyroid follicular cells require to store their hormones in the colloid
Require exocytosis to secrete them into the colloid, endocytosis to re-uptake it, then exocytosis again to secrete them into the bloodstream
187
What are thyroid hormones activated by?
TSH
188
What is the structure of TSH?
Much like the gonadotropins, (family II adenohypophyseal hormones) TSH requires an alpha-subunit to bind to its beta-subunit to be active
189
What are the factors effecting TSH release?
TRH (thyrotropin releasing hormone from the hypothalamus), T3 and T4 (thyroid hormones, negative feedback)
190
True/False? TRH is the largest peptide hormone
False. Smallest (glu-his-pro)
191
What are the functions of TSH?
Stimulates thyroglobulin, T3, and T4 synthesis
192
What is thyroglobulin (TG)?
A large protein containing many tyrosine residues and is commonly iodinated. Precursor to T3 and T4
193
Prolonged/chronic increase in TSH leads to what?
Hypertrophy (increase in size) and hyperplasia (increase in number) of thyroid follicle cells. Causes goiters in the absence of T3 and T4
194
Why are goiters caused by low T3 and T4?
Iodine deficiency causes a decreased synthesis of T3 and T4, which causes increased TSH (T3 and T4 have negative feedback on TSH), which leads to hyperplasia of the gland
195
Spell T3 and T4
T3: triiodothyronine
T4: tetraiodothyronine
196
Describe the iodination of TG and how it relates to thyroid hormones. What are the steps?
The iodination of Tyr residues of TG allows these Tyr residues to be cleaved into individual T3 and T4 molecules. Tyr > monoiodotyrosine > diiodotyrosine
2x diiodotyrosine = T4 - iodine = T3
monoiodotyrosine + diiodotyrosine = T3
197
How is T4 converted to T3?
Deiodinases remove an iodine group
198
(T3/T4) is the active thyroid hormone
T3
199
What are the four major steps for the synthesis of thyroid hormones?
0. TSH binds GPCR and increases cellular cAMP
1. Iodide trapping via the iodide pump
2. Oxidation of iodide (I-) to iodine (I2) by iodide peroxidase
3. Iodination of tyrosyl residues cleaved from TG, makes MIT and DIT
4. Oxidative coupling of iodinated tyrosines (dimerize) and release into the colloid
200
What is the role of peroxidase in the synthesis of thyroid hormones? How is it activated and what does it need to function?
Oxidizes I- to I2 using hydrogen peroxide generated by the pentose-phosphate pathway. Activated through phosphorylation by peroxidase kinases and requires H2O2 to function
201
How is T3 synthesized? Which pathway is more common to synthesize it?
Oxidating coupling of MIT and DIT, or deiodination of T4; deiodination
202
(T3/T4) is the major hormone synthesized by thyroid hormone synthesis pathway
T4, with minimal T3
203
Where is T4 deiodinated? What is the point of T4 if it is the inactive form?
Outside of the thyroid gland; has a longer half-life than T3
204
What are the functions of thyroid hormones?
- metamorphosis in amphibians
- normal growth
- metabolic functions like thermogenesis and maintenance of BMR
- protein synthesis
205
Thyroidectomy in tadpoles results in what? How is it treated?
They do not metamorphose; treated with T4 to start metamorphosis
206
What does a thyroidectomy in birds and mammals result in? How is it treated?
Growth retardation, skull malformation, delayed tooth eruption, insufficient nervous system, and delayed ossification of long bones; treat with T4 before 15 days of age
207
What is congenital hypothyroidism? How is it treated?
Insufficient T4 from birth, may be treated with thyroid replacement before 6 weeks of age, otherwise mental retardation
208
What are the metabolic functions of the thyroid hormones?
Responsible for oxygen consumption, thermogenesis, maintenance of BMR, protein synthesis, positive nitrogen balance (anabolism: building molecules), lipolysis and increase in [fatty acids] in blood
209
Calorigenesis is caused by what?
Thyroid hormones increase oxygen consumption and heat production
210
In mammals, prolonged exposure to the cold causes: (pathway)
Neuroendocrine reflex > increase in TRH > increase in TSH > increase in T4 and T3 production > thermogenesis
211
Describe the structure of GnRH and where it is secreted from
Decapeptide secreted by the hypothalamus, first four and last two residues are highly conserved
212
Who discovered GnRH?
Andrew Schally and Roger Guillemin both independently discovered it
213
Why is it important to note the high level of amino acid residue conservation in the amino acids of GnRH? What about the variable residues?
AA 1-4 and 9-10 are highly conserved, which means they serve a key biological function while 5-8 are highly varied and depend on species (specificity)
214
How does GnRH get to the pituitary to exert its effect?
It is transported through the hypothalamic-hypophyseal portal system and is released in a pulsatile manner to stimulate release of gonadotropins FSH and LH
215
True/False? GH is released steadily over the course of one's life
False. Released pulsatorily such that it is only released during initial growth and puberty, then stops
216
True/False? GnRH is released steadily over time and increases during puberty
False. Like GH, it is released in a pulsatory manner during puberty
217
What was the initial belief regarding the function of GnRH?
Only released LH (called LHRH), but was later discovered to stimulate the release of FSH too
218
List a few things GnRH analogs can be used to treat (name 2)
- precocious and delayed puberty
- hypogonadism
- anovulation
- amenorrhea
- premenstrual syndrome
- inadequate luteal function
- endometriosis
- hormone-dependent neoplasia
219
What are the stimulatory and inhibitory molecules used to regulate GnRH release?
Stimulatory: GABA, Kiss peptins, and gonadal steroids
Inhibitory: Dopamine, opioids, and gonadal steroids
220
GABA (stimulates/inhibits) dopamine, the action of which (stimulates/inhibits) _____________
Inhibits; stimulates GnRH
221
What stimulates Kiss peptin, and how does Kiss peptin interact with related hormones?
Estrogen stimulates Kiss peptin, which then stimulates GnRH
222
Androgens have a/an (stimulatory/inhibitory) effect on the hypothalamus through the stimulation of ______________
Inhibitory; opiates
223
Estrogen increases the secretion of which gonadotropin? How is this interaction mediated?
LH; mediated by the production of Kiss peptins, which stimulate GnRH, which then stimulates LH release
224
How do true contraceptive pregnancy pills work?
They secrete high levels of both estrogen and progesterone, which inhibit ovulation due to the inhibition of LH and FSH
225
A surge in androgens causes what effect on its stimulatory hormones?
Inhibits pulsatory release of GnRH, LH, and FSH
226
What are the gonadal peptides?
Inhibin and activin
227
Where are gonadal peptides synthesized? What do they regulate?
Produced in the gonads (ovaries and testes); specifically regulate FSH
228
Which family do gonadal peptides belong to?
Transforming growth factor beta superfamily (TGF-β)
229
Describe the action by inhibin
Inhibin inhibits secretion of FSH without effecting LH. May effect GnRH
230
Describe the action of activin
Activin stimulates secretion of FSH independent of LH and GnRH, as well as other actions (beyond scope)
231
Describe ovarian follicular development from a broad perspective (do not consider follicular structure)
1. Multiple primary oocytes within the ovary develop into follicles
2. Most follicles degenerate except a few
3. The remaining follicles become Graafian follicles (mature), then one oocyte re-initiates meiosis until it is arrested again in metaphase II
4. The singular mature follicle ruptures and the egg is released, the rest of the follicles degrade
5. The corpus luteum forms and releases progesterone
232
Primary oocytes are arrested in which phase of development?
prometaphase I
233
What is follicular atresia?
Degeneration of the ovarian follicle and oocyte
234
Describe Graafian follicle development
1. A primary oocyte from the resting pool initiates follicle development
2. Primary follicle
3. Granulosa cells (around the egg) and Theca cells (outer layer) become more numerous to make the secondary follicle
4. Large space forms between granulosa cells (antrum) that fills with fluid
5. Follicle enlarges to 20-25mm in diameter with a larger antrum and granulosa cells line the egg and the antrum while Theca cells remain outside (preovulatory/Graafian follicle)
235
As follicles mature into Graafian follicles, what happens to basal steroid hormone levels?
They increase (specifically estrogen)
236
How long is the menstrual cycle?
25-30 days
237
What are the two phases of menstruation? What event marks the end of one and beginning of the other?
Follicular phase (12-16 days) and luteal phase (10-16 days); separated by ovulation
238
Describe GnRH levels in follicular phase and explain why
Low at the beginning, but steadily rises and peaks just before ovulation (high Kisspeptins because of high estrogen)
239
Describe GnRH levels in luteal phase and explain why
Start high and rapidly diminishes to very low levels (low Kisspeptins because of low estrogen because of low LH)
240
Describe FSH levels in follicular phase and explain why
FSH levels higher than LH at the beginning (activin produced by follicular cells stimulates FSH release), then levels drop below LH (inhibin peaks) and peaks just before ovulation (peak caused by surge of GnRH, which is simulated by Kiss peptins released due to high estrogen)
241
Describe LH levels in follicular phase and explain why
LH remains steady until it reaches its peak just before ovulation (peak of GnRH, which is brought about by high Kisspeptin, stimulated by high estrogen)
242
When do oocytes complete meiosis II?
After fertilization
243
Describe FSH levels in luteal phase and explain why
Remains low (high inhibin, low LH and follicles are gone)
244
What determines which follicles develop into Graafian follicles?
FSH receptor capacity (more receptors = more stimulation by FSH = bigger follicle)
245
Describe LH levels in luteal phase and explain why
Remains low (combination of estrogen and progesterone inhibits LH)
246
Describe estrogen levels in follicular phase and why
Start low but gradually increase because FSH + LH, peaks just before ovulation (high LH because of high GnRH, follicles produce estrogen)
247
Describe GnRH levels at ovulation and explain why
High GnRH (high estrogen produced by mature follicle = high Kisspeptins which stimulate GnRH)
248
Describe FSH levels at ovulation and explain why
Peak at ovulation (high GnRH because of high Kisspeptins because of high estrogen produced by follicular cells because of high LH, low inhibin high activin)
249
Describe LH levels at ovulation and explain why
High (high GnRH because of high Kisspeptins because of high estrogen)
250
Describe estrogen levels at ovulation and why
High because of high LH because of GnRH
251
Describe estrogen levels in luteal phase and why
Gradual decrease because of low LH caused by combination of estrogen and progesterone, then peak caused by corpus luteum, then gradual decrease again because of its degradation and low LH
252
Describe progesterone levels in follicular phase and why
Low because of inhibin and no corpus luteum
253
Describe progesterone levels at ovulation and why
Low because of inhibin and no corpus luteum
254
Describe progesterone levels in luteal phase and why
High because of corpus luteum, then progesterone dramatically drops because of corpus luteum degredation
255
When is the uterine lining shed?
At the beginning of the follicular phase and end of luteal phase (low estrogen, FSH, LH, progesterone)
256
When does the uterine lining start regrowing?
When estrogen levels start increasing because estrogen is being produced by follicular cells
257
What is the function does the corpus luteum serve?
Progesterone and estrogen production and release
258
When does basal body temperature increase during the menstrual cycle?
Right after ovulation, and this heat it maintained until the next cycle starts
259
What is the function of inhibin in regards to follicular development?
It apoptoses non-dominant follicles that don't have enough FSH receptors
260
Describe inhibin levels throughout the menstrual cycle
Follicular phase: starts low, then increases before ovulation (causes a drop in FSH)
Ovulation: low-ish levels, peak in FSH
Luteal: low until it peaks mid-luteal phase, which then drops again, low FSH
261
The corpus luteum is composed of what cells? What do they produce?
Luteal cells, which develop from old granulosa and theca cells; produce estrogen and lots of progesterone
262
What happens to hormone levels if pregnancy occurs?
Secretion of hCG (human chorionic gonadotropin) causes prolonged secretion of progesterone and estrogen
263
What is hCG produced by?
The chorion (outer layer of the embryo)
264
What molecule may abortion pills contain to induce uterine lining shedding?
RU486, which is a competitive antagonist of progesterone
265
What is important to note about the structure of steroid hormones? How do they differ from each other?
Their precursor molecule is cholesterol; differ only by ring structure and side chains
266
What is a key feature of steroid hormones?
They are lipid soluble
267
Describe the synthesis of testosterone from cholesterol. Where does this synthesis take place?
1. Cholesterol undergoes side chain cleavage into pregnenolone (C21)
2. Pregnenolone is catalyzed by 3β-HSD into progesterone (C21)
3. Progesterone is catalyzed by 17α-hydroxylase into 17α-hydroxyprogesterone (C21)
4. 17α-hydroxyprogesterone is catalyzed by C17, 20-lyase into androstenedione (C19)
5. androstenedione is catalyzed into testosterone (C19)
Synthesized in both male and female gonads
268
What is the full name of 3β-HSD?
3β-hydroxysteroid dehydrogenase
269
Describe the synthesis of corticosteroids from cholesterol. Where does this synthesis take place?
1. Cholesterol undergoes side chain cleavage into pregnenolone (C21)
2. Pregnenolone is catalyzed by 3β-HSD into progesterone (C21)
3. Progesterone is catalyzed into corticosteroids (C21)
Synthesized in the adrenal cortex
270
What happens to testosterone in the testes?
5α reductase converts it into DHT in the Leydig cells
271
Which hormones are synthesized in the ovaries and testes besides testosterone? How many carbons does each have, which precursor is used, which enzyme is used, and what is the name of this process?
Estrone (C18): precursor is androstenedione
Estradiol (C18): precursor is testosterone
Aromatase catalyzes the reaction, and this process is called aromatization
272
Why do some obese males have 'moobs'?
They produce female sex hormones due to the excess adipose tissue (fat), which is where aromatization occurs in males
273
Progestogens have how many carbons? What hormone is technically under this category, then?
21; corticosteroids (also C21)
274
Androgens have how many carbons? When in the cholesterol to testosterone pathway do androgens first appear?
19; conversion of 17α-hydroxyprogesterone (C21) into androstenedione (C19) by C17, 20-lyase
275
Estrogens have how many carbons? What cells produce them in females?
18; granulosa and theca cells within the developing follicle
276
Downregulation of which enzymes occurs during luteal phase?
17-alpha hydroxylase
277
What are the functions of estrogens?
- primary reproductive features (reproductive organs)
- secondary reproductive organs (breasts and mammary glands)
- increased deposition of adipose tissue in breasts, thighs, and buttocks
- build the endometrium
278
What are the functions of progestogens?
- prepare uterus for implantation by maintaining the lining
- reduces uterine contraction and prevents expulsion of implanted ovum
- promotes secretion of nutrients by cells lining the fallopian tube
- promotes development and secretion of alveolar tissue and general breast swelling
279
What are the functions of testes?
- produce spermatozoa
- secrete androgens
280
True/False? Testosterone is only found in males
False. Found in females too (precursor for estradiol)
281
What are the functions of androgens?
- primary and secondary male sexual characteristics
- stimulate development of prostate, seminal vesicle, bulbourethral gland, Sertoli cell maturation and androgen binding protein synthesis
- maintains reproductive tract
- stimulates spermatogenesis
- increases libido
- regulates gonadotropin secretion
- anabolic growth
- fusion of epiphysis
- voice change
- hair growth
282
What are the androgens?
Testosterone and DHT
283
What is the full name for DHT?
Dihydrotestosterone
284
True/False? Females are born with all the germ cells they will have throughout their lifetime
True. They lose most by birth and even more by puberty (300-400k left at puberty)
285
When does menopause occur?
When the ovaries run out of eggs and hormonal changes stop the menstrual cycle
286
Do males go through menopause?
No, they go through andropause, which is a steady decrease in testosterone, but spermatogonia continuously divide throughout life
287
What are the side effects of menopause?
- hot flashes
- urinary problems (change in muscle tone)
- vaginal dryness (lack of estrogen)
- mood swings and sleep disturbances
- increase in heart disease and stroke
- osteoporosis (estrogen is important for Ca2+ deposit)
288
What are the pancreatic metabolism-controlling hormones?
Insulin and glucagon
289
What are the adrenal metabolism-controlling hormones?
Cortisol (glucocorticoids) and epinephrine
290
What are they hypophyseal and gonadal hormones that regulate metabolism?
- GH (energy-mobilizing)
- T3 and T4 (increase BMR)
- prolactin (hyperglycemic)
- estrogens (increase body temp when ovulating)
291
Why is glucose important for living organism function?
Provides ATP through glycolysis + other pathways and brain is only able to use it for energy
292
What are some glucose storage macromolecules?
- glycogen (glucose polymer, polysaccharide in animals)
- cellulose (glucose polymer, polysaccharide in plants)
- fat (fatty acid polymer)
293
Glycolysis is the pathway responsible for what?
Energy mobilization from glucose
294
Gluconeogenesis is the pathway responsible for what?
Synthesis of glucose from non-carbohydrate intermediates (fatty acids and amino acids)
295
Glycogenesis is the pathway responsible for what?
Storage of glucose into glycogen
296
Glycogenolysis is the pathway responsible for what?
Glucose mobilization from glycogen
297
Where does glycolysis happen? TCA and cellular resp?
Cytosol; mitochondrial matrix
298
True/False? The pancreas is purely endocrine
False. Has both exocrine (enzymes) and endocrine cells
299
What are the endocrine cells of the pancreas called?
The islets of Langerhans
300
What are the cell types of the islets of Langerhans? What does each produce?
- α cells: glucagon
- β cells: insulin and amylin
- δ cells: gastrin and somatostatin
301
What kind of hormone is Insulin? Glucagon?
Both protein hormones
302
Insulin is the main _________________ hormone, but not the only one. The other is _____________
Hypoglycemic; amylin
303
Insulin is (catabolic/anabolic). What does this mean?
Anabolic; its action facilitates the building of molecules (glycogen, for example)
304
What is the main function of insulin? How does it do this?
Reduces blood glucose level by:
- increasing glucose transport into insulin-sensitive cells
- enhancing cellular utilization of glucose
- enhancing storage of glucose
- enhancing utilization of amino acids
- promoting fat synthesis
305
What is the main pancreatic enzyme that antagonizes insulin?
Glucagon
306
What is the main function of glucagon?
Acts on liver cells to increase the synthesis of glucose and results in increased circulating glucose level (gluconeogenesis and glycogenolysis)
307
Glucagon is known as a __________________ hormone
Hyperglycemic
308
How is insulin synthesized?
Proinsulin is cleaved in two spots
309
What is proinsulin?
A C-shaped protein where its ends are linked by two disulfide bonds. When cleaved, the linked ends remain together and form insulin
310
How are β Cells activated to produce their hormone? What hormone is produced?
Glucose binds to the calcium-dependent membrane receptor (glucose-sensing receptor); insulin and amylin
311
What are the inhibiting factors of β cells?
- insulin
- somatostatin
- catecholamines
312
What are the activating factors of β cells?
- amino acids
- high blood glucose
- glucagon (small amount)
- incretins
- gastrin
- secretin
- cholecytokinin (CCK)
313
What are the inhibiting factors of α cells?
Amylin
314
What are the activating factors of α cells?
- catecholamines
- low blood glucose
315
What is the function of amylin?
Inhibits glucagon production by inhibiting α cells (lowers blood glucose)
316
Explain how catecholamines exert their effects on β cells and α cells
Catecholamines bind α receptors on β cells, inhibiting them, and bind β receptors on α cells, activating them
317
What are the incretins? What action do they have on metabolism?
GIP (gastric inhibitory peptide) and GLP-1 (glucagon-like peptide-1); stimulate insulin production
318
Why does glucagon exert a stimulatory effect on insulin?
Allows for fine-tuning of homeostasis so that the blood sugar doesn't rise too high
319
What is the main function of GLP-1?
It increases receptor sensitivity to insulin so that the biological response increases in magnitude
320
What is the main factor stimulating insulin release?
Blood glucose level
321
Describe a glucose vs. time graph of a normal patient and a diabetic patient
Glucose peaks 30min after eating in both, and quickly drops off in normal patients. In diabetic patients, the peak is even greater and drops significantly slower
322
What is the effect of insulin on GLUT 4? What is GLUT 4?
It increases GLUT 4 activity; a glucose membrane transporter (transports glucose into cells) located on insulin-sensitive cells
323
What are the insulin-sensitive cell types?
Muscles, heart, and adipose cells
324
Where does insulin have no effect on glucose transport?
Renal tubules, RBC, intestinal mucosa, **liver**, and brain (not insulin-sensitive)
325
Is glucose the only molecule that is effected by insulin?
No, amino acids and fatty acids also have increased transport
326
What are the five functions of insulin?
1. increase solute (glucose, amino acids, fatty acids) transport
2. increase glucose oxidation (glycolysis) in adipose tissue
3. increase glycogenesis in muscle cells
4. increase lipogenesis
5. increase protein synthesis
327
How does insulin increase glycogenesis?
It stimulates hepatic (liver) glucokinase activity (phosphorylates glucose) and glycogen synthase activity (glycogen synthesis)
328
Glycogenesis and glycogenolysis are for (short/long)-term energy storage and mobilization, respectively
Short-term
329
What are insulin's effects of lypogenesis?
Increases glucose transport into adipose cells and activity of lipoprotein lipase, which increase fat synthesis. Decreases fat oxidation and lipolysis (breakdown of fat)
330
What are insulin's effects on protein synthesis?
Increases amino acid transport into fat cells and protein synthesis. Decreases protein catabolism
331
What is Type I diabetes mellitus?
Insulin-dependent diabetes. It's an autoimmune disorder in which the immune system destroys β cells (causes insulin deficiency)
332
What is Type II diabetes mellitus?
Non-insulin-dependent diabetes. It's characterized either by a deficiency of insulin or by reduced insulin receptor responsiveness to insulin
333
What effect may corticosteroid drugs have on Type II diabetes?
They make it worse because corticosteroids increase blood glucose levels, which is the problem affecting people with Type II diabetes
334
True/False? Hyperglycemic hormones work separately
False. They work synergistically
335
Describe the synergistic effects of hyperglycemic hormones
If alone, hyperglycemic hormones don't produce as much of a response. However, when they are present together, their effects amplify (not just additive)
336
Describe hypoglycemic control of glucagon secretion
1. hypoglycemia causes low intracellular [glucose], leading to a reduction in ATP generation via glycolysis
2. reduction in ATP-sensitive K+ channel activity
3. increase in intracellular K causes depolarization (becomes less negative inside) of the cell membrane and activation of voltage-dependent Ca2+ channels
4. increased influx of Ca2+ triggers the secretion of glucagon through exocytosis
337
What are the three actions done by glucagon?
1. increase glycogenolysis
2. increase gluconeogenesis
3. increase lipolysis
338
Describe how glucagon increases glycogenolysis
Binds its GPCR, activating adenylate cyclase, producing cAMP. cAMP stimulates glycogenolysis and inhibits lipid synthesis and glycogenesis
339
Describe how glucagon increases gluconeogenesis
Glucagon causes deamination of amino acids in the liver and their conversion to carbohydrates
340
Gluconeogenesis is the mobilization of glucose due (short/long)-term stress or starvation. Why?
Long-term; it is the catabolism of proteins and fat needed for muscles and other metabolic functions, so it is the last straw
341
The effects of glucagon on glucose mobilization are (isolated/synergistic). Why?
Synergistic; glucose mobilization through three pathways (glycogenolysis, gluconeogenesis, and lipolysis)
342
What are the hormones of the adrenal medulla?
- epinephrine
- norepinephrine
- dopamine
343
The hormones of the adrenal medulla are what class or hormones?
Catecholamines
344
Which two adrenal medulla hormones are also produced in the brain? What are their functions?
Norepinephrine and dopamine; neurotransmitters (neurocine, neuroendocrine, and endocrine)
345
What are the hormone classes of the adrenal cortex?
Glucocorticoids, mineralocorticoids, and androgens (steroids)
346
Why are androgens produced in the adrenal cortex?
They are important for initiating puberty in females, as their ovaries do not yet produce estrogen (androgens are aromatized into estrogen)
347
What are the organizational levels of the adrenal glands?
Inner medulla and outer cortex
348
What is the name of the tissue that secretes adrenal medulla hormones? What kind of hormones are they?
Chromaffin tissue; catecholamines
349
What are the layers of the adrenal cortex? Outside to inside
1. Zona glomerulosa
2. Zona fasciculata
3. Zona reticularis
350
The zona glomerulosa secretes which hormones? They belong to which adrenal cortex hormone class?
Corticosterone and aldosterone; mineralocorticoids
351
The zona fasciculata secretes which hormones? They belong to which adrenal cortex hormone class?
Cortisol; glucocorticoids
352
The zona reticularis produces which hormones? They belong to which adrenal cortex hormone class?
Androgens; steroid hormones
353
Describe the synthesis of catecholamines
1. Phenylalanine is converted to tyrosine by phenylalanine hydroxylase
2. Tyrosine is converted into DOPA by tyrosine hydroxylase
3. DOPA is converted into dopamine by dopa decarboxylase
4. Dopamine is converted to NE by dopamine beta-hydroxylase
5. NE is converted to E by PNMT
354
The chromaffin requires which key enzyme of the catecholamine synthesis pathway to produce all of its hormones?
PNMT (converts NE into E)
355
What is the full name of PNMT?
Phenylethanolamine-N-methyltransferase
356
What is the rate-limiting step in catecholamine synthesis? Why is this the rate-limiting step?
Tyrosine hydroxylase converting tyrosine into DOPA; feedback inhibition by dopamine and NE
357
What is the full name of DOPA?
Dihydroxyphenylalanine
358
What are the two types of adrenergic receptors?
Alpha and beta
359
True/False? The adrenergic receptors are innervated together. Why or why not?
False. Innervated separately; must be stimulated separately because they are both sensitive to E and NE and thus would elicit a response at the same time
360
What is the role of epinephrine? Norepinephrine?
Both are sympathetic nervous system (fight or flight), but epinephrine is more general than NE
361
What does E do to blood glucose? Cardiac output?
Increases both blood glucose (hyperglycemic) and heart rate
362
How does E redistribute the blood supply? Why is E able to have different effects on tissue types?
More blood flow (vasodilation) to heart and muscles, restricted flow (vasoconstriction) to skin and viscera; reaction to E depends on receptor type
363
How does E effect breathing?
Dilation of bronchioles for less restricted airflow
364
What are the five ways E causes hyperglycemia?
- hepatic glycogenolysis
- hepatic gluconeogenesis
- inhibition of insulin release through inhibiting beta cells with alpha receptors
- stimulation of glucagon release through stimulating alpha cells with beta receptors
- stimulation of ACTH release (glucocorticoids like cortisol mobilize glucose)
365
What are the effects of NE and E on alpha adrenergic receptors?
Stimulation of: gluconeogenesis, dilation of pupils, sweating, GH secretion, arterial constriction, muscle contraction)
Inhibition of: insulin secretion
366
What are the effects of NE and E on beta adrenergic receptors?
Stimulation of: glycogenolysis, lipolysis, renin secretion, arteriolar dilation, cardiac contractility (heart rate), muscle relaxation, glucagon secretion, thyroid hormone secretion
367
Alpha adrenergic receptors are more sensitive to (NE/E)
NE
368
Beta adrenergic receptors are more sensitive to (NE/E)
E
369
True/False? The hormones of the adrenal cortex are synthesized in different layers depending on the type of hormone
True. Mineralocorticoids produced in zona glomerulosa, glucocorticoids produced in zona fasciculata, and gonadocorticoids produced in zona reticularis
370
Name the axis that described control of the adrenal glands
Hypothalamo-hypophyseal-adrenal axis (HHA axis)
371
The HHA axis is stimulated by
CRH (stimulates ACTH release), catecholamines/opioids (depends on receptor type), and stress
372
The HHA axis is inhibited by
Glucocorticoids (negative feedback) and catecholamines/opioids (depends on the receptor)
373
Describe the HHA axis
Hypothalamus releases CRH, which goes to the pituitary via the hypothalamo-hypophyseal portal system. This stimulates ACTH production, where it then stimulates the adrenal cortex to make corticoids
374
What are the metabolic effects of glucocorticoids?
Cortisol increase glucose mobilization via gluconeogenesis, inhibition of cellular uptake of glucose, and other catabolic effects like proteolysis, lipolysis, and glycogenolysis
375
When cortisol stimulates gluconeogenesis, where does it happen? Where do the substrates come from?
Happens in liver cells (hepatocytes); amino acids come from proteolysis of muscle proteins in muscle cells, free fatty acids come from lipolysis in adipose cells
376
Why are hepatocytes the main epicenter for gluconeogenesis?
Their membranes are leaky (highly permeable to solutes), so it is easy for amino acids and free fatty acids to get inside to be catabolized
377
The hyperglycemic effects of the sympathetic nervous system are what?
Synergistic
378
What are the two cells of the nervous system?
Glial cells and neurons
379
What are microglia?
Macrophages within the CNS
380
What are the macroglia?
Astrocytes, oligodendrocytes, and Schwann cells
381
What are astrocytes?
The most abundant macroglia that act as support for neurons (nutritive and physical) and are a fundamental component of the blood brain barrier
382
What are oligodendrocytes?
Cells that create the myelin sheath in the CNS that increase the conductivity of the cell
383
What are Schwann cells?
Individual cells that wrap around PNS axons that create the myelin sheath to increase axon conductivity
384
Where does input of a signal occur on a neuron?
Dendrites
385
Where does the integration of a signal occur on a neuron?
Soma/cell body
386
Where does conduction of a signal occur on a neuron?
Axon
387
Where does the output of a signal occur on a neuron?
Synaptic bouton/terminal
388
What are the five components of a neuron?
- dendrites
- soma
- axon
- axon terminals
- cell membrane
389
Describe the functional units of the cell membrane
Phospholipid bilayer where the heads of the phospholipids are polar (hydrophilic) and the tails are non-polar (hydrophobic)
390
What is a hydration shell? What part of a phospholipid has a hydration shell?
A layer of H2O molecules that surround a polar molecule; polar, hydrophilic head
391
The selective properties of the membrane and the hydration shell allow for the development of what?
A membrane potential (separation of charges)
392
A voltmeter with the recording electrode outside of the cell will show what voltage? Why?
0mV; no difference between recording electrode and reference electrode
393
A voltmeter with the recording electrode inside of the cell will show what voltage? Why?
-65mV; inside of the cell is more negative than the outside
394
What is the source of the membrane potential?
The separation of ions
395
Which ions are involved with maintaining membrane potential? Which are the main contributors?
**Na+, K+**, Ca2+, Cl-, and charged organic anions (A-)
396
What is important to note about calcium?
It is divalent (2+)
397
Compared to the outside of the cell, there are (more/less) Na+ ions inside the cell
Less (more outside)
398
Compared to the outside of the cell, there are (more/less) K+ ions inside the cell
More (less outside)
399
Compared to the outside of the cell, there are (more/less) Cl- ions inside the cell
Less (more outside)
400
Compared to the outside of the cell, there are (more/less) Ca2+ ions inside the cell
Less (more outside)
401
Compared to the outside of the cell, there are (more/less) A- ions inside the cell
More (less outside)
402
What assumptions can we make about the mammalian neuron with our knowledge of the squid axon?
They have similar ion concentrations inside and outside the cell, so they are somewhat comparable
403
What is the Na+/K pump?
An active transporter (ATPase) that maintains the separation of charges by transporting both Na+ and K+ against their concentration gradients (3Na+ out, 2K+ in)
404
What is the concentration gradient?
The driving force of ion movement depending on concentration differences
405
What allows for the membrane potential to become static at rest?
The K+ channel that lets K+ exit the cell to maintain electrochemical balance
406
According to the chemical gradient, which direction do Na+, K+, Cl-, and A- want to go? Which ones are able to permeate the membrane?
K+ and A- want to leave, Na+ and Cl- want to go inside; only K+ can permeate (leak channel)
407
The K+ leak channel makes the inside of the cell more (negative/positive). Why?
Negative; the positive charges are leaving the cell
408
What are the three effects of the movement of ions?
- contributes to the membrane potential
- effect on ion concentrations
- depletion of concentration differences
409
True/False? The concentration gradient for the ions relevant to the membrane potential is static/unchanging
True. Differences are so great that the movement of ions does not affect the overall gradient
410
Decreased K+ membrane permeability (increases/decreases) resting membrane potential. Why?
Increases (more positive); if less K+ ions are leaving the cell, their positive charges will accumulate and vice versa
411
Decreased Na+ membrane permeability (increases/decreases) resting membrane potential. Why?
Decreases (more negative); if less Na+ ions are getting into the cell, the inside will be more negative and vice versa
412
What is the resting membrane potential when K+ permeability = 0? Na+ permeability = 0?
When PK+ = 0, RMP = Na+ potential; When PNa+ = 0, RMP = K+ potential
413
What is the simplified version of Coulomb's Law?
A force is generated between two charges that either repel (same charge) or attract (opposite charge)
414
What is the electromotive force of Na+, K+, and Cl- ions?
Na+ and K+ are attracted to the inside of the cell, and Cl- is repelled by the inside of the cell
415
What direction are the driving and electromotive forces for K+ ions? What happens if PK+ is infinite? What is the resting membrane potential at this point?
Driving force is leaving the cell (concentration gradient) and EMF is entering the cell (-ve charge); if PK+ is infinite, an equilibrium is reached when enough K+ ions leave the cell to make the EMF the same magnitude as the driving force but in opposite directions (as K+ leaves due to DF, the cell becomes more negative, which pulls them back in at the same rate); RMP = K+ potential
416
What direction are the driving and electromotive forces for Na+ ions? What happens if PNa+ is infinite? What is the resting membrane potential at this point?
Driving force is entering the cell (concentration gradient) and EMF is entering the cell (-ve charge); if PNa+ is infinite, an equilibrium is reached when enough Na+ ions enter the cell to make the EMF the same magnitude as the driving force but in opposite directions (as Na+ enters due to DF, the cell becomes more positive, which repels them at the same rate); RMP = Na+ potential
417
What is the definition of the Nernst Equation?
The relation between the concentration difference of a permeating ion across a membrane and the membrane potential at equilibrium (no net movement)
418
What is the Nernst Equation at 18C?
Membrane potential = E(mV) = 58log(Cout/Cin)
419
What is the Nernst Equation at 37C?
Membrane potential = E(mV) = 61log(Cout/Cin)
420
If the valence of an ion is 2, how do we manipulate the Nernst equation?
Divide the constant (58 or 61) by 2
421
If an ion has a negative charge, how do we manipulate the Nernst equation?
Multiply by -1 or do log(Cin/Cout), though I prefer just multiplying it by -1
422
True/False? The Nernst equation can be used for multiple ions at a time
False. Use for one ion at a time
423
What equation can be used to determine membrane potential when taking all ions into account? Why?
Goldman Equation; It takes into account the permeability and concentration of each ion
424
Which ion makes the greatest contribution to the RMP? Why?
K+ because it has the greatest permeability and greatest potential
425
A decrease in [K+] inside the cell results in a more (positive/negative) RMP. Explain why
Positive; Decreasing [K+] inside the cell causes the driving force to decrease. This causes the membrane potential to be more positive because less K+ ions are leaving the cell
426
A decrease in [K+] outside the cell results in a more (positive/negative) RMP. Explain why
Negative; Decreasing [K+] outside the cell causes the driving force to increase. This causes the membrane potential to be more negative because more K+ ions are leaving the cell
427
A decrease in [Na+] inside the cell results in a more (positive/negative) RMP. Explain why
Positive; Decreasing [Na+] inside the cell causes the driving force to increase. This causes the membrane potential to be more positive because more Na+ ions are getting into the cell
428
A decrease in [Na+] outside the cell results in a more (positive/negative) RMP. Explain why
Negative; Decreasing [Na+] outside the cell causes the driving force to decrease. This causes the membrane potential to be more negative because less Na+ ions are getting into the cell
429
An increase in [K+] inside the cell results in a more (positive/negative) RMP. Explain why
Negative; Increasing [K+] inside the cell causes the driving force to increase. This causes the membrane potential to be more negative because more K+ ions are leaving the cell
430
An increase in [K+] outside the cell results in a more (positive/negative) RMP. Explain why
Positive; Increasing [K+] outside the cell causes the driving force to decrease. This causes the membrane potential to be more positive because less K+ ions are leaving the cell
431
An increase in [Na+] inside the cell results in a more (positive/negative) RMP. Explain why
Negative; Increasing [Na+] inside the cell causes the driving force to decrease. This causes the membrane potential to be more negative because less Na+ ions are getting into the cell
432
An increase in [Na+] outside the cell results in a more (positive/negative) RMP. Explain why
Positive; Increasing [Na+] outside the cell causes the driving force to increase. This causes the membrane potential to be more positive because more Na+ ions are getting into the cell
433
Define voltage
The separation of charge (mV)
434
Define current
The movement of charge (mA)
435
Define resistance
The reduction of charge movement (Ohm)
436
What is Ohm's Law?
V = IR
437
What part does the cell membrane play in generating voltage?
It separates the charges by acting as an insulator (selectively permeable)
438
What part does the cell membrane play in generating current?
Allows ions to move across when specific criteria are met (voltage-gated ion channels)
439
What part does the cell membrane play in generating resistance?
Number of ion channels dictates resistance (more channels = less resistance)
440
What is capacitance? What is the formula and what does each variable represent?
The ability to hold charge; C = q/V; C is capacitance (F), q is charge, and V is voltage (mV)
441
What are the parts of a capacitor? What parts of the membrane correlate with each?
A plate that holds positive charge (extracellular space), a plate that holds negative charge (intracellular space), and an insulator between then (cell membrane)
442
If a capacitor is allowed to charge for an infinite amount of time, what voltage will it end up having? What happens when the battery is removed?
The same voltage as the battery that is supplying the charges; The plates will still hold their charges despite not being attached to the battery
443
What are the properties of a capacitor?
- can hold charge that is equal to the input voltage
- charging delay (requires time to reach maximum voltage)
444
What does a voltage over time graph look like for a current applied when there is no capacitor in the system?
The change in voltage will look the same as the change in current
445
What does a voltage over time graph look like for a current applied when there is a capacitor in the system? Why?
The change in voltage requires time to reach the maximum voltage (slowly increasing slope that looks like a hill); Capacitors require time to build up their separation of charges (voltage)
446
True/False? Unlike charging a capacitor, depleting a capacitor of charge is instantaneous
False. It requires an amount of time that is a function of the length constant (λ)
447
What is the variable that describes the time required to reach 63% of maximum voltage? What is the formula to calculate it?
Tau (τ), which is the time constant; τ = RmC, where τ = time constant, Rm = membrane resistance, and C = capacitance
448
Where is ΔV the greatest? What happens to it as it moves down the cell? How can we prove this?
ΔV is the greatest at the point of stimulus (where the current was introduced) and it dissipates at it moves away from this site; Take two recording electrodes, put one next to the current pulse generator and the other a bit farther away. The ΔVmax of the closer one will be much greater than the farther one
449
Provide three examples of passive electrical properties
- time-delayed change in membrane potential
- distance degradation
- temporal summation
450
What is the variable the describes the distance from the point of stimulation where ΔV is at 37% of its maximum? What is the formula to calculate it?
The length constant (λ); λ = SQRT(Rm/Ri), where Rm = membrane resistance and Ri = internal/axial resistance
451
As Rm increases, what happens to λ? Why?
λ increases because less charge is leaving through the cell membrane if its resistance is greater, so the charge can travel further before it reaches 37% of its maximum voltage
452
As Ri increases, what happens to λ? Why?
λ decreases because there are obstacles within the cell that resist the current
453
As Rm increases, what happens to τ? Why?
τ increases because it takes longer for the capacitor to charge if there's greater resistance against the current
454
When a current is introduced to a cell, what initially happens to the charge?
It splits, so half of the charge goes one way and half of the charge goes the other way
455
A smaller Ri indicates what about the axon?
Greater diameter of the axon
456
What is spatial summation?
PSPs at different areas on the same cell are additive and thus may generate an action potential if they reach threshold
457
What is temporal summation?
PSPs at the same time on the same cell are additive and thus may generate an action potential if they reach threshold
458
What happens if there is an EPSP and an IPSP at the same time?
They neutralize each other
459
What is the key property of dendrites that allows graded potentials to become action potentials?
Temporal and spatial summation/subtraction
460
What is the main function of the soma?
To integrate the signal from the dendrites, which will propagate the signal to the axon hillock for action potential generation if the signal is strong enough
461
What allows the depolarization of the axon hillock when an action potential is generated?
A high density of voltage-gated Na+ channels
462
Describe the structure of the voltage-gated Na+ channel
It is a long peptide consisting of four domains. Each domain has six transmembrane segments, and the fifth and sixth segment within each domain is separated by a P-loop
463
Which part of the voltage-gated Na+ channel forms the pore?
P-loop
464
Which part of the voltage-gated Na+ channel acts as the voltage sensor?
The fourth transmembrane segment within each of the four domains (four sensors in total)
465
Describe the structure of the voltage-gated K+ channel
It consists of four homopeptides, where each has 6 transmembrane segments. Segment 5 and 6 are separated by a P-loop in each peptide
466
What is the difference between the VG Na+ and K+ channels? Similarities?
The Na+ channel is a single peptide with four domains, whereas the K+ channel is a homotetramer, K+ opens and closes much slower, and Na+ has an inactivated state; They both have P-loops between segments 5 and 6, and the voltage sensor is the fourth transmembrane segment
467
Which part of the voltage-gated K+ channel forms the pore?
P-loop
468
Which part of the voltage-gated K+ channel acts as the voltage sensor?
The fourth transmembrane segment within each of the four peptides (four sensors in total)
469
What are the two properties that allow ion channel selectivity? Which properties contributes most to selectivity?
- ion physical size
- **hydration shell**
470
Which ion is bigger, K+ or Na+?
K+
471
Which ion has a larger hydration shell, K+ or Na+?
Na+
472
Describe how the ion channel determines selectivity using the hydration shell
The amino acids lining the pore of the channel are positioned in a way so that they replace where each water molecule sits in the shell, which doesn't require any energy
473
An action potential is a (passive/active) electrical event. What does this mean?
Active; the signal is propagated, so it doesn't dissipate
474
What is the resting phase of an action potential?
The membrane potential is at rest, so ions are at equilibrium
475
What is the depolarization phase of an action potential?
The membrane potential becomes less negative and reaches the threshold potential
476
What is the rising phase of an action potential?
If threshold is met, the membrane potential dramatically increases and Na+ floods in
477
What is the peak/overshoot phase of an action potential?
This is the maximum voltage of the membrane potential where the inside of the cell is the most positive
478
What is the falling phase of an action potential?
After overshoot, membrane potential drops rapidly as K+ leaves the cell
479
What is the after-hyperpolarization phase of an action potential?
After membrane repolarization, the cell undershoots and becomes hyperpolarized (more negative than resting potential)
480
What is the recovery phase of an action potential?
After hyperpolarization, the resting membrane potential is restored
481
What happens when a strong current, strong enough to cause an action potential, is applied for a long time?
Action potentials will fire one right after another
482
True/False? Action potentials do not degrade with distance
True
483
What prevents the action potential from propagating in both directions in a naturally-stimulated scenario?
Na+ inactivate after they open, so they cannot be reopened
484
Compare the permeability of K+ vs. Na+ at resting potential. Why?
PK > PNa; K+ leak channels
485
Compare the permeability of K+ vs. Na+ at rising phase. Why?
PNa > > PK; VG Na+ channels open
486
True/False? Overshoot is able to reach +54.5mV, which is the Na+ potential
False. While yes, this is the Na+ potential, the membrane potential can't reach this number because the K+ leak channels are still letting positive charge out of the cell
487
What are the three states of the VG Na+ channel?
Closed, open, inactivated (follows that order and loops back to closed)
488
Compare the permeability of K+ vs. Na+ at falling phase. Why?
PK > > PNa; K+ channels are open and Na+ channels are inactivated
489
Why does the VG K+ channel open after the VG Na+ channel?
- requires higher depolarization to open than Na+ channels (higher threshold)
- opening kinetics are slower than that of Na+ channels (by the time they open, Na+ channels are inactivated)
490
Compare the permeability of K+ vs. Na+ at undershoot phase. Why?
PK > PNa; K+ leak channels are still open
491
Compare the permeability of K+ at resting potential vs. after-hyperpolarization. Why?
PK ah > PK r; leak channels and VG K+ channels are still open during after-hyperpolarization because the VG channel takes time to close
492
Compare the permeability of K+ vs. Na+ at recovery/repolarization phase. Why?
PK > PNa; VG K+ channels are closed, but the leak channels are still open
493
True/False? Like the VG Na+ channel, the VG K+ channel also inactivates after opening
False. It only closes due to the change in membrane potential
494
Compare the directionality of AP propagation in naturally-stimulated cells and experimentally-stimulated cells
Natural: unidirectional because of Na+ channel inactivation
Experimental: bidirectional because Na+ channels upstream haven't been inactivated yet
495
What are the refractory periods of an AP?
Absolute and relative
496
What is the absolute refractory period? When is it and what causes it?
The point in an AP where it is impossible to generate another one; during falling phase; VG Na+ channels are inactivated
497
What is the relative refractory period? When is it and what causes it?
The point in an AP where it is more difficult to generate another one; after falling phase (after-hyperpolarization and onwards); increased PK causes the cell to require a greater pulse because the membrane potential is further from the threshold
498
How does the relative refractory period reflect decreased membrane resistance?
Because of the increased K+ permeability, there is less resistance of the membrane for keeping the ions inside the cell, so a greater current is required to counteract the lower resistance to generate another AP
499
Define conduction velocity
How fast the charge moves from point A to point B
500
Define conduction velocity in terms of repeated action potentials
How many times an AP must occur along the length of the axon to reach point B
501
Conduction velocity is a function of what variable? Why?
λ; The greater the length constant, the less APs needed to reach point B, so the greater the conduction velocity
502
What are the three factors effecting conduction velocity?
- axon diameter
- myelination
- temperature
503
How does an increased axon diameter effect conduction velocity?
More space within the axon allows for better movement of charges, so less internal/axial resistance = greater λ = greater conduction velocity
504
How can axons of the same diameter have different conduction velocities?
Myelination
505
Myelination results in ____________ conduction
Saltatory
506
Define saltatory conduction
When action potentials are propagated along the axon at intermittent spots due to increased ion permeability at those spots
507
Why does saltatory conduction increase conduction velocity
Myelination increases membrane resistance between nodes of Ranvier, so the charges stay inside (do not leak out, which would dissipate the charge) = increased λ = increased conduction velocity
508
How does temperature increase conduction velocity?
Molecules/ions move faster at higher temperatures
509
What does an action potential look like at higher temperatures?
It is skinnier
510
If a large quantity of Na+ was added to the extracellular space, what would be the difference in the action potential? Why?
The peak amplitude would be more positive because the driving force of Na+ getting into the cell would be greater
511
If a large quantity of K+ was added to the extracellular space, what would be the difference in the action potential? Why?
The after-hyperpolarization would be shorter because the driving force for K+ to leave the cell would be less, so less positive ions would leave the cell and thus the cell won't be as hyperpolarized. Also, the action potential would be reduced
512
What are the types of striated muscle?
Skeletal and cardiac
513
What is the main function of skeletal muscle?
Voluntary movement
514
What is the main function of cardiac muscle?
Oxygen transport and heart function
515
What is smooth muscle?
Tissue that makes up the intestines and blood vessels
516
The intestines are made up of (single/multi) units
Single
517
Blood vessels are made up of (single/multi) units
Multi
518
What is the order, from largest to smallest, of the parts of a skeletal muscle?
Skeletal muscle > fascicle > muscle fiber/cell > myofibril > sarcomere
519
Muscle fibers are (enucleated/multinucleated). How did they come to be like this? What advantage does this give these cells?
Multinucleated; fusion of precursor cells; allows for constant turnover of proteins
520
What is the main function of smooth muscle?
Digestion (intenstines)
521
What is the functional unit of a muscle cell?
Sarcomeres
522
What are the main structures found in a muscle cell?
- myofibrils
- nuclei
- many mitochondria
- transverse tubules
- sarcoplasmic reticulum
- sarcomeres (within myofibril)
- sarcolemma
523
What are the main constituents of sarcomeres?
Thick and thin filaments
524
What are the regions of a sarcomere?
- Z-disc
- I-band
- A-band
- H-zone
- M-line
525
Z-disc
Boundaries of each sarcomere
526
I-band
Only thin filaments (found adjacent to the Z-disc)
527
A-band
Region of thick and thin filament overlap
528
H-zone
Only thick filaments (found spanning the M-line)
529
M-line
Middle of the sarcomere with only thick filaments
530
Myofilaments are arranged in ____________ in a sarcomere
Parallel
531
When a muscle contracts, which regions change size? Which stay constant?
Shorten: I-band and H-zone
Stay: A band, M-line, Z-disc
532
Describe the general structure of a thick filament
Consists of myosin tails with heads that stick outwards (look like golf clubs) and spiral in rows around the thick filament
533
True/False? Myosin heads are spread evenly within the A band
False. There are no myosin heads in the center of the thick filament (area surrounding the M-line
534
Describe the structure of myosin
Consists of two heavy chain (heads and tails) and four light chains (two on each neck). Has 2 heads and 2 tails. Each head contains an ATPase domain and an actin/thin filament binding site. Each neck of the protein (between the heads and the tails) contains the essential and regulatory myosin light chains
535
What are the three types of proteins found on thin filaments?
G-actin, troponin, and tropomyosin
536
What is the main protein of thin filaments? What is it made of?
F (filamentous)-actin; G-actin monomers
537
What are the regulatory proteins of thin filaments? What do they regulate?
Tropomyosin and troponin; muscle contraction
538
How is tropomyosin associated with f-actin?
It wraps around the f-actin like a braid
539
How is troponin associated with f-actin?
It separates the f-actin and tropomyosin
540
What is the structure of troponin?
Contains 3 subunits: TN-T, TN-I, and TN-C
541
Describe the steps of cross-bridge cycling
1. ATP binds myosin heads
2. ATP hydrolysis by the APTase on the myosin heads positions the actin binding site on the myosin over the tropomyosin on the thin filaments
3. Ca2+ binds troponin, allowing actin and myosin to bind
4. Pi (inorganic phosphate) is released, so myosin pulls on the actin, moving it forward
5. ADP releases from the myosin
6. ATP binds myosin and releases the myosin from the actin
542
Which step of cross bridge cycling is the "power stroke"?
Step 4 (when Pi dissociates and the thin filaments move inwards)
543
Why is calcium needed for muscle contraction?
Once bound to troponin-C (TN-C), it moves tropomyosin out of the way of the actin and myosin binding sites
544
What happens to muscles if there is Ca2+, but no ATP?
Muscles will contract, but will stay bound together because there is no ATP to release them
545
What is rigor mortis?
A condition that occurs upon death where muscles stay contracted and rigid due to a lack of ATP to release the myosin heads from the actin (occurs during steps 4-6 of cross bridge cycling)
546
What is sliding filament theory?
The theory that muscle contractions are thick and thin filaments sliding past each other
547
You're a researcher in a muscle physiology lab. After a long day of experiments, you notice two unlabeled tubes. You know that each tube contains either:
Myosin and pure G-actin
Myosin and thin filaments
No ATP or Ca2+ was added to the tubes. You run an assay which allows you to isolate and identify myosin and whether it is bound to a second molecule. If it is, then that molecule will end up in the tube with the myosin.
Tube A: contains only myosin
Tube B: contains myosin and another molecule
Which tube is which?
Tube A contains myosin and thin filaments, because there is no Ca2+ to move the tropomyosin out of the way, so the myosin and actin can't bind.
Tube B contains myosin and G-actin because there is no tropomyosin in the way of the myosin and G-actin
548
Which regions of the sarcomere shorten during muscle contraction? Select all that apply:
A) sarcomere
B) A-band
C) I-band
D) H-zone
E) M-line
F) Z-discs
ACD
549
When is there a maximum force generated in a sarcomere?
When there is optimal overlap of the thick and thin filaments
550
Why does too much overlap of the thick and thin filaments cause little force generation? What about too little overlap?
While all myosin heads should be able to generate a power stroke, there is simply not enough room in a sarcomere if the sarcomere is already shortened; There would be no contact between the myosin and actin, so little to no force would be generated
551
Define excitation-contraction coupling
The relationship between depolarization and actual muscle contraction
552
What do motor neurons connect to?
Muscle fibers
553
What is the sarcolemma?
The cell membrane of muscle fibers
554
What is the sarcoplasmic reticulum?
A specialized endoplasmic reticulum
555
What is the role of the sarcoplasmic reticulum?
It regulates the storage, release, and re-uptake of Ca2+
556
What are transverse tubules?
Invaginations of the sarcolemma in striated muscle that are rich in ion channels
557
What is the role of transverse tubules?
Allow for propagation of electrical signals
558
What is a neuromuscular junction?
A chemical synapse that connects motor neurons and muscle fibers
559
What are the ion channels found on the pre-synaptic membrane at the synapse?
Voltage-gated Ca2+ channels
560
What are the ion channels found on the post-synaptic membrane at the synapse?
Ligand-gated Na+ channels, VG Na+ channels
561
Describe the steps that occur to cause muscular contraction, starting at the synapse and ending at SERCA
1. AP reaches the terminal and opens VG Ca2+ channels
2. Increased intracellular Ca2+ causes vesicles full of NTs to fuse with the pre-synaptic membrane
3. NTs enter synaptic cleft and bind ligand-gated Na+ channels on post-synaptic neuron
4. increased intracellular [Na+] causes depolarization of the membrane, opening VG Na+ channels, which further depolarize the cell (EPSP)
5. if EPSP is great enough, the depolarization will reach the DHP receptors within the T-tubules
6. activation of DHPR opens RYR channel on sarcoplasmic reticulum, releasing Ca2+ into the muscle cell
7. Ca2+ goes on to bind troponin. allowing for myosin to bind the actin and the sarcomere contracts
8. SERCA pumps Ca2+ back into the sarcoplasmic reticulum with ATP
562
What causes DHPR to open? What does this tell us about what kind of receptor it is?
Depolarization; voltage-gated
563
What is the neurotransmitter found at the neuromuscular junctions?
Acetylcholine (Ach)
564
Describe the steps of the termination of the contraction signal
1. Acetylcholinesterase (AchE) removes Ach from the synapse
2. lack of Ach causes ligand-gated Na+ channels to close, so the cell no longer depolarizes
3. DHPR becomes inactive and inactivates RYR, so Ca2+ cannot flow out of the sarcoplasmic reticulum
4. SERCA pumps Ca2+ back into the sarcoplasmic reticulum
565
Per contraction, how much Ca2+ leaves the sarcoplasmic reticulum on average?
40-60%
566
Noenicitinoid pesticides are a class of pesticide that target insect AchR. When ingested, they act as agonists of AchR and block Ach binding. These pesticides are not species specific, meaning they have unintended impacts on the physiology of non-target beneficial species. How might exposure to these pesticides impact excitation-contraction coupling in bumblebees? Select all that apply:
a) ligand-gated channels on the post-synaptic membrane will be constantly open
b) continuous calcium release from the sarcoplasmic reticulum will lead to continuous, unstoppable muscle contractions
c) sodium influx via VG channels on the post-synaptic membrane will be inhibited
AB
567
What is excitation-contraction coupling latency?
The delay between the peak of [Ca2+] within the cell and the peak of the force generated
568
The toadfish is a species that emits a call through the rapid contraction of muscles. What protein allows them to do this? Why do they require a rest period between calls?
Parvalbumin; rest allows the muscles to relax and replenish their calcium before another call
569
What is parvalbumin?
A calcium binding protein that corrals Ca2+ to the SERCA pumps
570
Compare calcium binding proteins in vertebrates and invertebrates
Vertebrates have parvalbumin, while invertebrates rely on other (unnamed) calcium binding proteins
571
Why do flying insects require specialized muscle fibers?
Flying muscles require a lot of fast muscle contractions, so these specialized muscle fibers allow for fast Ca2+ cycling
572
True/False? Muscle contraction and shortening are equivalent
False. A whole muscle can contract without shortening
573
Define a concentric contraction
A contraction that generates force and the muscle gets shorter
574
Define an eccentric contraction
A contraction that generates force and the muscle gets longer
575
Define an isometric contraction
A contraction that generates force, but stays the same length
576
Compare isometric contraction and isotonic contraction
Isometric contraction is when the muscle length stays constant throughout the period or force production, where isotonic contraction is when the muscle shortens at a constant force and velocity (only possible in lab contexts)
577
Draw the force x length curve for a whole muscle
See notes (whole muscle)
578
Why does the force of a muscle go up at maximum length?
Because of the elastic characteristic of muscle
579
What gives muscle its elasticity?
Tendons, sarcolemma, connective tissue sheath, and the myosin necks on thick filaments
580
How do the muscles of arboreal primates differ to the muscles of terrestrial primates?
Arboreal muscles are much much longer, which allows for greater muscular flexibility and elastic potential (longer muscles = more sarcomeres in series)
581
What is power?
Force x shortening velocity
582
What main factor determines the force a muscle can exert?
Myofibril cross-sectional area (greater area = more sarcomeres in parallel)
583
What main factor determines the velocity of a muscular contraction?
ATP hydrolysis rate and sarcomeres in series (more sarcomeres = longer muscle = faster contraction and greater elasticity)
584
Draw the force x velocity curve for a muscle
Should have Vmax at F = 0 and Fmax at V = 0 (see notes)
585
Draw the power on a force x velocity curve for a muscle
See notes
586
What is the trade-off between muscular force and velocity caused by?
Cross-bridge cycling
587
What are the sources of variation between species of their muscular force and length?
- speed of ATP hydrolysis rate at the myosin heads
- affinity of troponin-C for Ca2+
- muscle size
588
What does 'sarcomeres in series' mean?
Sarcomeres are attached one after another in the horizontal plane
589
Sarcomeres in series boost (force/speed). How?
Speed; if a single sarcomere shortens at rate x, then 3 sarcomeres in series shorten at rate 3x (the very ends of the myofibrils shorten at 3x, sarcomeres individually are x)
590
What does 'sarcomeres in parallel' mean?
Sarcomeres are placed above and below one another
591
Sarcomeres in parallel boost (force/speed). How?
Force; provide a greater cross-sectional area
592
Imagine you are the greatest sorcerer of your time. Halloween is just around the corner and you really want to be able to compete in your coven's pumpkin patch lift off, which has contestants compete to see who can lift the heaviest loads of pumpkins. You decide to mix up a potion that can give your muscles that extra "forceful" boost they need to win. Which ingredients listed below should you add to your potion to maximize power in your muscles?
Toads foot (increases number of sarcomeres in series)
Bat's wing (increases number of sarcomeres in parallel)
Purple slug mitochondria (increases the activity of your myosin ATPase)
Black widow silk (decreases the affinity of your troponin for calcium)
Toads foot, bat's wing, and purple slug mitochondria (each increase either force or velocity, which will both increase power since p = f x v)
593
What are the potentials of K+, Na+, and Cl-?
-75, +55, and -56mV, respectively
ZOOL 461
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Decks in class (4)
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