1
Q
What are stem cells and the different types?
A
- Stem Cells: have unique to differentiate into other cell types
- Pluripotent (embryonic stem cell): can differentiate into any cell line
- Multipotent: can differentiate into limited cell lines (ex: bone marrow)
2
Q
What are terminally differentiated cells?
A
- Terminally Differentiated: adult cell that enters into non-dividing state (ex: skeletal cells, neurons)
- Specialized stem cells can be present for repair mechanisms
3
Q
List the steps of the interphase, their main functions and how it is regulated.
A
- Interphase
- Gap1 Phase: growth phase where cells can enter into G0 (no division)
- S Phase: replication
- Gap2 Phase: growth phase
- Checkpoints are regulated by [Cdk]
4
Q
List the steps of the mitosis, their main functions and how it is regulated.
A
- Mitosis
- Prophase: duplicated centrosomes; mitotic spindles form (microtubules)
- Metaphase: nuclear envelope breakdown; chromosomes align
- Anaphase: chromatids separate
- Telophase: nuclear envelope reforms
- Cytokinesis: cells divide using actin mechanism
- Checkpoints are regulated by [Cdk]
5
Q
What is cell signaling and how does the process work?
A
- Change in external environment → Change in receptor binding → Secondary messengers → amplify response → adapts gene expression
6
Q
What are the types of intracellular signaling and how do they work?
A
- Intercellular Signaling
- Contact-dependent: membrane-bound receptor interaction
- Paracrine: mediator molecule secreted to local environment
- Synaptic: neurotransmitters (think ACh!)
- Endocrine: hormones through bloodstream
7
Q
What are the differences between Eukaryotic and Prokaryotic cells?
A
- Eukaryotic has membrane-bound organelles for specialized functions, nucleus, and mitochondria while prokaryotic utilizes cytosol for all functions. Both have PMs.
8
Q
What is the function of cytoskeleton and what are the types?
A
- Provides cell stability and movement
- Types
- Actin
- Intermediate filaments
- Microtubules
9
Q
What are the three phases of polymerization for cytoskeleton?
What is dynamic instability?
How do kinesin and dynein play a role?
Name a disease associated with cytoskeleton.
A
- 3 phases of polymerization
- Nucleation: assembly of monomers
- Elongation: rapid growth at (+) end
- Steady-state: equal rate of polymerization and de-polymerization
- Dynamic instability: rapid de-polymerization to cause separation of mitotic spindle.
- Polymerization and de-polymerization occurs at (+) end and nucleation occurs at (-) end
- Kinesin moves things to (+) end {cell surface is +}
- Dynesin walks things back to (-) end {centrosome is -}
- Disease: Hereditary Spherocytosis
10
Q
Describe the function and properties of the cell membrane.
A
- Expands with budding and fusion events
- Impermeable to most ions and water molecules
- Contains pumps and channels which allow movement of ions, molecules, and proteins
- Glycoproteins on ECM interact with EC environment
11
Q
Describe the properties and function of the nucleus. Name a disease associated with the nucleus.
A
- Description: made up of nuclear envelope and nuclear pores
- Function: storage of DNA
- Disease: Hutchinson Gilford Progeria
12
Q
Describe the properties and function of ribosomes.
What is the SRP’s role in ribosome function?
A
- Description: cytosol and ER-bound organelles
- Function: protein synthesis
- SRP: signal recognition particle targets synthesized protein to ER
13
Q
Describe the properties and function of the endoplasmic reticulum (ER).
A
- Description: network of tubules that acts as the outer bilayer of the nuclear envelope
- Function: processes proteins and lipid biosynthesis
- Ca++ storage and detoxification
14
Q
Describe the properties and function of the golgi apparatus. Name diseases often associated with the golgi.
A
- Description: structure is dependent on microtubules with bi-directional transport from cis to trans-face
- Function: supplies membrane and is site of glycosylation
- Disease: congenital diseases associated with glycosylation such as seizures
15
Q
Describe the properties and function of the lysosome. Name a disease associated with the lysosome.
A
- Description: contains hydrolytic enzymes
- Function: utilizes endocytosis (foreign macromolecules), macropinocytosis (fluid near PM), autophagy (cell components), and phagocytosis (foreign large particles/microorganisms)
- Disease: Lysosomal Storage Disease
16
Q
Describe the properties and function of the mitochondria. Name two types of diseases associated with the mitochondria.
A
- Description: contains inner and outer membrane layers with own DNA
- Function: generates ATP
- Diseases
- Lufts
- Age-Related Degenerative Diseases (Parkinson’s and Alzheimer’s)
17
Q
Describe the properties and function of the peroxisome. Name a disease associated with the peroxisome.
A
- Description: single membrane with dense matrix
- Function: oxidative reactions with hydrogen peroxide and FAs
- Disease: Zellweger Syndrome Spectrum
18
Q
Describe the properties and function of the cilia/flagella. Name a disease associated with the cilia/flagella.
A
- Description: structural arrangement (9+2) of microtubules that extend from basal body
- Function: lines tracts to move mucus and cause movement (sperm)
- Disease: Dyskinesia (Kartagener’s Syndrome)
19
Q
What is the general mechanism of direct transport between membrane enclosed organelles?
How are compartments in the cell diverse?
A
- Vesicles bud from marked specific sites contain cargo proteins that are delivered to another membrane compartment by fusion.
- Compartment diversity
- Some require cytoskeletal elements to maintain shape
- Small vesicles – diffusion, large vesicles – cytoskeleton tract
20
Q
What are the types of trafficking pathways?
A
- Types of trafficking pathways
- Biosynthetic: secretory pathway from ER to golgi to PM
- Endocytosis: PM to early/late endosomes to lysosomes
- Retrieval: backflow of selected components is maintained
21
Q
Where do clathrin coats, COP I coats, and COP II coats transport to and from?
A
Clathrin
- Transport: PM to early endosomes and Golgi to lysosomes
COP I
- Transport: Golgi to PM and Golgi to ER
COP II:
- Transport: From ER to Golgi
22
Q
What is the structure of clathrin coats?
A
made of triskelion (3 light, 3 heavy chains) that self assembles to a hexagonal structure
23
Q
What is the assembly process of clathrin coats?
A
- Arf-GEF recruits Arf-ADP → Arf-ATP → inserts into membrane → fatty acid tail exposure → clathrin recruitment → dynamin pinches off vesicle using accessory proteins and PIP2
- Phorsphorylation of PIPs to PIP2s are also involved in recruitment
24
Q
What is the disassembly process of clathrin coats?
A
- Heat shock protein (Hsp70) is an ATPase stimulated by Auxilin → ATP hydrolyzes into ADP → Hsp70 uses energy from ATP hydrolysis to peel off coat
- PIP2s are dephosphorylated to PIPs weakening coat-membrane interactions
25
What is the COP I assembly process?
* Arf-GEF recruits Arf-ADP → Arf-ATP → inserts into membrane → fatty acid tail exposure → COPI recruitment → dynamin pinches off vesicle using accessory proteins and PIP2
* Phorsphorylation of PIPs to PIP2s are also involved in recruitment
26
What is the COP I disassembly process?
* Heat shock protein (Hsp70) is an ATPase stimulated by Auxilin → ATP hydrolyzes into ADP → Hsp70 uses energy from ATP hydrolysis to peel off coat
* PIP2s are dephosphorylated to PIPs weakening coat-membrane interactions
27
What is the COP II assembly process?
* Sar1-GEF recruits Sar1-GDP → Sar1-GTP → inserts into membrane → fatty acid tail exposure → COPII recruitment → dynamin pinches off vesicle using accessory proteins and PIP2
28
What is the COP II dissassebly process?
* Heat shock protein (Hsp70) is an ATPase stimulated by Auxilin →ATP hydrolyzes into ADP →Hsp70 uses energy from ATP hydrolysis to peel off coat
* PIP2s are dephosphorylated to PIPs weakening coat-membrane interactions
29
What is the function, structure of SNARE proteins, and the fusion process?
* Function: acts as tethers to bring membranes together for fusion; this is a Ca++ dependent process
* Structure
* V-SNARE (transport vesicle made up of one polypeptide chain)
* T-SNARE (target membrane made up of three polypeptide chains)
* Fusion Process
* T-SNARE traps V-SNARE
* Energy from four helix bundle drives membrane fusion
30
What is the disassembly process of SNAREs?
* NSF (i.e. NEM sensitive factor) and accessory proteins react with two cysteine residue to block activity
* Hydrolyzes ATP to destabilize four-helix bundle
31
What is the function of RAB GTPases?
* Function: molecular switches that control protein-protein interactions to allow for specific vesicle targeting
32
What is the process of RAB GTPases?
* Rab-GEF (could be a SNARE or tether) recruits Rab-GDP on donor membrane → Rab-GTP → Rab-GTP inserts into donor membrane → transport vesicle/budding forms/occurs → Rab effector binds Rab-GTP → fusion → Rab-GDP
33
What are the effectors of Rab GTPases?
What is the idea of cooperative action for Rab GTPases?
* Effectors
* Motors, SNAREs, Tethers
* Cooperative Activation
* When subunits (ex: SNAREs and Rabs) work together
34
What is the process of protein exit from the ER and transport to and from the Golgi?
How does membrane thickness play a role?
* ER exit sites to Golgi are with COPII; Golgi exit sites to ER are with COPI
* Budding exit sites contain cargo receptors that bind to exit signals on cargo proteins (but are not necessary)
* Membrane thickness (i.e. cholesterol) plays role in sorting transmembrane proteins
* TM proteins in thick membranes goes to PM and TM proteins in thin membranes stays in ER and Golgi
35
What are ER resident proteins and how do they work?
* ER Resident Proteins: marked by signal sequences on protein (i.e. KDEL or KKXX)
* Return to ER through retrieval pathway
* Affinity in ER Resident Receptors
* More acidic pH in Golgi increases affinity of receptor for ER resident proteins
36
How do chaperone proteins work and provide an example?
* Chaperone Proteins: fold proteins and keep misfolded proteins from leaving ER
* Example: BiP act as chaperones for ABs (but also think of CFTR protein)
37
Where does glycosylation occur and what are the two main types?
* Glycosylation occurs in Golgi
* Golgi more prominent in cells that secrete large amounts of glycoproteins (i.e. goblet cells in small intestine)
* Features
* N-linked glycosylation: sugar attached to asparagine reside
* O-linked glycosylation: sugar attached to serine or threonine residue
38
What is the importance of glycosylation?
* Importance
* Prevents approach of proteases
* Prevent aggregation
* Promotes cell signaling
* Transport – M6P is linked to lysosomal hydrolases to target to lysosome
39
What is the transport mechanism for lysosomal hydrolase?
* Acid hydrolases are only active at low pH
* Vacuole ATPase pumps H+ against gradient into lysosome
* M6P is used to tag lysosomal hydrolase precursors from ER in the Golgi
* M6P binds to M6P receptor in Golgi → early endosome → lysosome through Clathrin
* Addition of GlcNAc-P to M6P in the early endosome to release hydrolase precursor
* M6P receptor is recycled back to Golgi
40
What are the features of phagocytes?
What types of professional phagocytes?
What is the ingestion process of phagocytes?
**Phagocytosis**
* Greater than 250nm diameter
* Professional phagocytes (components of WBCs)
* Macrophages: apoptotic cells
* Neutrophils: foreign organisms
* Ingestion Process
* Attachment (through tagging) → Engulfment (formation of phagocytotic cup through the use of GTPase-dependent actin protrusions) → Fusion with Lysosome (degradation)
41
What is pinocytosis?
* Ingestion of fluids
* Less than 100nm diameter
42
What is receptor-mediated endocytosis and give the process using LDL particles?
* Clathrin mediated
* Example: LDL particles
* LDL receptors on ECM of PM recognize LDL particle
* LDL receptor binds adaptor protein and clathrin coat assembles
* Transported to early endosomes then lysosomes
* LDL receptor dissociates from LDL particle in early endosome and receptor is recycled back to PM
* Free cholesterol enters cytoplasm
* Promotes homeostasis by inhibiting LDL receptors and shutting down cholesterol synthesis when [LDL]cell is high
43
What is transcytosis used for and provide an example of where it would be used?
* Used in polarized epithelial cells to transfer macromolecules from one extracellular space to another (apical to basolateral)
* Example: transferring of ABs from mother’s blood to baby’s blood
44
What are the two types or regulated pathways and provide examples of where each would be used?
* Signal Mediated Diversion to Lysosomes
* M6P receptor example
* Signal Mediated Diversion to Secretory Vesicles
* Occurs in specialized cells for the release of neurotransmitters and hormones
45
What is the constitutive pathway and how does it work?
* Constitutive Pathway
* Does not have any signals to mediate pathway
* All vesicles are destined for PM
* Mature secretory vesicles can selectively aggregate in trans-Golgi, but aggregation signal is unknown
46
What's the hierarchy of protein structures?
* Primary
* Amino acid sequence, location of disulfide bonds, covalent structure of the protein
* Secondary
* Alpha helices, beta sheets, turns
* Tertiary
* Includes position of AA side chains
* Includes interactions between secondary structures and folding arrangement of the various domains
* Quaternary
* Combination of two or more polypeptide chains to form complete unit
47
What are the properties of amino acids and what are the amino acids under each property?
Non-Polar AAs
* GAVLIMP WF – “**GAV**in **LIMP**ed with **W**arm **F**ingers”
* Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Proline, Tryptophan, Phenylalanine
Polar
* STCYNQ – “**S**ome**T**imes **C**ats **Y**ell **N**ot **Quietly**”
* Serine, Threonine, Cysteine, Tyrosine, Asparagine, Glutamine
Charged
* DEKRH – “**D**umb **E**vil **K**ings **R**ule **H**ell”
* Aspartate, Glutamate, Lysine, Arginine, Histidine
48
Describe the peptide bond and the restrictions it puts on protein structures.
* Partial double bond character (planar) because of resonance of electrons between carbonyl oxygen, carbonyl carbon and the nitrogen
* Peptide bond is rigid with no freedom of rotation, but rotation is allowed around bonds of the alpha-carbon
* Nitrogen—alpha-carbon bond is called phi
* Carbonyl—alpha-carbon bond is called psi
49
How does the Ramachandran Plot work?
* Uses Van der Waals’ radii and bond length to determine which bond angles result in appropriate energies
* More colored area of the plot means more flexibility of bond
50
What are the differences between Glycine and Proline and how do they act in terms of providing flexibility/rigidity in proteins?
* Glycine and Proline are different because glycine only has a hydrogen as side-chain, allowing for extreme flexibility
* Proline cannot form any hydrogen bonds, so it is the most limited in flexibility
51
What are the secondary structures in proteins and what are their properties?
* Alpha-Helix
* Right-handed, 3.6 AAs per turn, i to i+4 parallel hydrogen bonds maximizes local structure
* Compact packing of backbone, with no hole down the middle and side chains facing outwards
* Beta-Sheets
* Hydrogen-bonds are interstrand and perpendicular to the long axis of the chain
* Beta-branched AAs (V, I, and T) fit better in sheets than in helices
* Sheets stack on each other
* Sheets are more flexible than helices
52
Compare and contrast transmembrane protein sequences and cytosolic protein sequences?
* Transmembrane protein sequence
* Twenty nonpolar AAs in an alpha-helix are needed to span the lipid bilayer (multi-pass proteins require one side of each helix to be non-polar)
* Cytosolic protein sequence
* Hydrophobic inside, hydrophilic outside
53
What is the role of hydrogen bonds in the folding process in proteins?
* Hydrogen bonds
* Dipole-dipole interaction
* H-bonds must be nearly linear to maximize energy of stabilization (remember: alpha helix and beta sheets)
* Forms extensive network of H-bonds in protein backbone
54
What is the role of hydrophobicity in the folding process of proteins?
* Hydrophobicity
* Water prefers to interact with itself over hydrophobic groups, allowing for minimal exposure of hydrophobic groups
* Spherical protein shapes only expected if only hydrophobicity drives protein structure
55
What is the role of configurational entropy in protein folding?
* Configurational entropy
* There is great entropic cost (requires energy) to fixing orientation angles of backbone and sidechains to a single unique value
* Instead of just being random, the native conformation must overcome significant barriers to formation
56
What's the importance of amino acid sequences not being able to fold by themselves?
* These amino acid sequences only become structured in the presence of other compounds, (other proteins or ligands).
* As such, these sequences are critically important to regulation of a protein’s activity, and activation or suppression of signaling pathways.
* These sequences are the most frequent sites of post-translational modification, and provide easily accessible conformations that can bind to other proteins for signaling cellular conditions.
57
Describe the forces that allow proteins to bind to ligands?
* The interior is shielded so the protons only go where they are supposed to, not toward the water
* There are electrostatic interactions, hydrophobic interactions, and hydrogen bonds on the interior caused by AA residues in the active site
* Everything is close and complementary in shape and polarity
58
Describe the equlibirum binding curve and the role of Kd.
* Kd is the concentration of ligand at ½ maximal saturation
59
Describe how allostery works in ligand binding.
Define positive/negative cooperativity. Provide an example.
* Ligand binding at one site can influence binding of a second ligand at another site
* Positive cooperativity is when binding of the first ligand increases affinity for the second ligand
* Negative cooperativity is when the binding of the first ligand decreases the affinity for the second ligand
* The second ligand can be the same or different molecule from first
* Example: myoglobin versus hemoglobin
60
What effect do increases and decreases in pH, DPG, and temperature have on oxygen binding curves?
61
Describe how enzymes work and the thermodynamics of the process.
* Enzymes lower the transition state barrier to help proteins reach their native conformation much faster
* Highest affinity for enzyme is when protein is in transition state conformation
* An exergonic reaction can be coupled with an endergonic reaction to make the process spontaneous overall (negative change in G)
62
What are two types of effects of enzyme specificity?
What are two theories of enzyme interaction?
* Proximity effect – bringing two substrates close
* Orientation effect – orientation of substrate with respect to active site side chains
* Theories: lock and key model and induced fit model
63
How do Acid-Base catalysis help enzymatic reactions?
* Acid-Base Catalysis
* Transition state may require the loss or gain of a proton on the substrate
* Active sites frequently have an acid or base residue at the active site to contribute to binding and catalysis
* Histidine is especially popular because it can donate a proton on one side and accept a proton on another
64
How does covalent catalysis help enzymatic reactions?
* Transient formation of a covalent bond between the enzyme (or cofactor) and the substrate
65
How does metal ion catalysis help enzymatic reactions?
* Ions bind to substrates to orient them properly for reaction
* Mediates redox reactions by utilizing metal ion’s ability to lose and gain electrons
* Can neutralize the charge
66
What is the Michaelis-Menton Equation and what is KM?
What does a high/low KM indicate?
* KM is the measure of dissociation/affinity of the ES complex
* KM= ES breaking apart/ ES staying together
* High KM means the ES is breaking apart, and has low affinity
* Low KM means denominator is larger, meaning ES staying together and has high affinity
* KM is typically regarded as ½ the VMAX or the maximum rate a reaction of the substrate using its enzyme can occur
67
What is a competitive inhibitor and how does the lineweaver-burk plot look like?
* Competitive
* Competes with substrate at active site to bind enzyme
* Inhibitors have structures similar to the substrate or product
68
What is non-competitive inhibition and what is the lineweaver burk plot for it?
* Inhibitors bind to free E and ES at same affinity
* Can also be called a “mixed” inhibitor as it is both a competitive and non-competitive inhibitor
69
What is uncompetitive inhibition and what is the lineweaver burk plot for it?
* Uncompetitive
* Inhibitors bind only to the ES complex and block product formation
* Increase substrate affinity
70
Relate enzyme inhibition/activation in relation to drug mechanism Allostery, Enzyme Inhibition, and Drugs
* Allosteric enzymes are found in the most carefully regulated steps in metabolism
* These are good targets for therapeutics because they already have sites on enzyme to regulate activity
* Drugs are not competitive for the active site but binds to allosteric molecule site, thus having less side affects
71
Describe irreversible inhibition.
* Irreversible inhibitors bind to the active site, deeming the active site non-functional
* Only way to restore is by synthesizing new enzyme
72
Describe transition-state inhibitors and why they are so effective.
* Compounds have chemistry similar to the transition state rather than to substrate or product.
* Slow enzyme conformation change and extremely tight, effective irreversible binding
73
What is the function of chaperones in the folding process and what are some types?
* Prevent inappropriate association/aggregation/misfolding by binding and supporting
* Some couple ATP hydrolysis to unfold non-native structures
* Chaperone concentration greatly increases with stress response to help fold greater number of proteins being synthesized
* Types: box chaperones, prolyl-peptide isomerases, and disulfide isomerase enzymes
74
Describe how amyloid fibrils form in protein folding diseases. What are the two types that were discussed?
* The amyloid itself is toxic where ever it accumulates.
* In AL, the many different light chains of an AB are misfolded and aggregate together to form amyloid fibrils.
* Familial transthyretin amyloidosis is caused by misfolded transthyretin monomers that denature and aggregate into amyloid.
* Mechanistically, the growth of the amyloid fibril can break cell membranes and kill cells due to its rigid “cross-bridge structure”.
75
What are the three steps of translation and what occurs at each step?
* This is a highly regulated process
* Initiation: Methionine (only one codon codes for M) attaches to initiator tRNA
* Elongation: AAs are added in the peptidyl transfer center
* A-site and P-site scrutinize codon-anticodon interactions to ensure correct AA is added; 3rd position has less fidelity/wobble position
* Deacylated tRNA is translocated from P-site to E-site, where it finally dissociates
* Termination: stop codon indicates end of polypeptide synthesis
76
What do aminoglycosides do near the A-site during translation?
* Aminoglycosides near A-site on the ribosome decreasing fidelity, so wrong amino acids end up being incorporated much more often, producing nonfunctional proteins
77
What are the two types of mutations and what are the nature of both?
* Conservative mutations code for AAs with similar properties as the wild type.
* Because mutations in the third nucleotide position in the codon (wobble position) can code for the same AA, the protein sequence does not change.
* Sometimes a deletion of a codon
* Non-conservative mutations code for AAs that have differing properties
* Frameshift or truncation mutations
78
What is the nature of post-translational modifications and their role in protein function?
Provide an example that demonstrates the importance of post-translational modifications.
* **M**odulates – alters the the activity of a protein
* **A**dds – incorporates non-protein functional groups to protein structure (i.e. heme centers in hemoglobin)
* **R**ecruits – recruits other proteins into complex
* **T**argets – routes protein molecules to a specific cellular location
* Example: insulin receptor
* Phosphorylation of tyrosine residue on tyrosine kinase receptor opens up active site allowing ATP binding
79
How does ubiquitin regulated protein degradation work?
* Ubiquitin can be added to lysine residues in proteins
* Only when a polyubiquitin chain (single ubiquitin added at a time) is present can the protein recognized for degradation
* Monoubiquitin used for transport or signaling
* Labeled protein targeted to proteasome
80
What are the functions of the parasympthetic nervous system?
* Normal homeostasis
* Slows things down
* Rest and digest
* Can control specific things
* Body cavities and head
81
What does the parasympathetic nervous system act on?
* Cardiac muscle
* Smooth muscle
* Organs/salivary glands
* Does not act on blood vessels
82
Where does the parasympathetic originate from?
Cranio-sacral region (brainstem and coccyx)
83
Describe the neuron anatomy of the parasympathetic ganglia.
* Long preganglionic neuron
* Short postganglionic neuron near the organ
84
What is the preganglionic receptor and its transmitter in the parasympathetic nervous system?
What are the agonists and antagonists?
* **Nicotinic (ACh) [NN]**
* **Agonist:** nicotine
* **Antagonist**: curare
85
Describe the receptor structure and ion channel associated with preganglionic parasympathetic nervous system?
* **Nicotinic (ACh) [NN]**
* Ligand gated sodium channels composed of 5 subunits surrounding the sodium channel
* Binds to receptor on two of the subunits, activating channel to allow Na+ to rush in and cause depolarization
86
What are the functions of the sympathetic nervous system?
* Stress management
* Speeds things up and drives the autonomic system forward
* Fight or flight
* System fire alarm
* Entire body
87
What does the sympathetic nervous system act on?
* Cardiac muscle
* Smooth muscle
* Organs/adrenal medulla
* Arteries
* Sweat glands
88
Where does the sympathetic originate from?
Thoraco-lumbar area of the spine
89
Describe the neuron anatomy of the sympathetic ganglia.
* Short preganglionic neuron with synapse paravertebrally
* Long postganglionic neuron to the organ
90
What is the preganglionic receptor and its transmitter in the sympathetic nervous system?
What are the agonists and antagonists?
* **Nicotinic (ACh) [NN]**
* **Agonist:** nicotine
* **Antagonist**: curare
91
What does the adrenal sympathetic act on?
Adrenal Medulla
92
What does the somatic nervous system act on?
Skeletal muscle
93
What is the preganglionic receptor and its transmitter in the somatic nervous system?
What are the agonists and antagonists?
* **Nicotinic (ACh) [NM]**
* Agonist: nicotine
* Antagonist: curare
94
Describe the receptor structure and ion channel associated with the preganglionic strucure in the sympathetic nervous system.
* **Nicotinic (ACh) [NN]**
* Ligand gated sodium channels composed of 5 subunits surrounding the sodium channel
* Binds to receptor on two of the subunits, activating channel to allow Na+ to rush in and cause depolarization
95
Describe the receptor structure and ion channel associated with the preganglionic neuron in the somatic nervous system?
* **Nicotinic (ACh) [NM]**
* Ligand gated sodium channels composed of 5 subunits surrounding the sodium channel
* Binds to receptor on two of the subunits, activating channel to allow Na+ to rush in and cause depolarization
96
Which nervous system utilizes muscarinic receptors for its postganglionic neurons?
Parasympathetic
97
Describe the structure of the muscarinic receptor.
7-Transmembrane G-Protein Coupled Receptor: span membrane 7 times with GPCR that facilitates intracellular secondary messaging
98
How do the odd muscarinic receptors act and how many subtype receptors are there?
* M1, M3, M5
* Gq is the alpha subunit of the G protein
* Activation results in stimulation of PIP2 hydrolysis – increasing Phospholipase C and increasing DAG (which increases Ca2+) - increasing PKC
* Muscle contraction (i.e. persistalsis)
99
How do the even muscarinic receptors act and how many subtypes are there?
* M2, M4
* Only act on the heart
* Gi is the G protein
* activation results in inhibition of adenylyl cyclase through Gi, which enhances K+ conductance flow from inside to outside the cell down the gradient to hyperpolarize the cell
* May also decrease Ca2+ influx through Gi closing Ca2+ channels and decreasing the release of transmitter
100
What is the agonist and antagonist to muscarinic receptors?
* Agonist: muscarine
* Antagonist: atropine
101
What are the steps in the synthesis of epinephrine?
Tyrosine → L-Dopa → Dopamine → Norepinephrine → Epinephrine
102
What neurotransmitter do sweat glands, adrenal medulla, and adernergic receptors use?
* Sweat Glands: ACh
* Adrenal Medulla: Epi
* Adernergic: Norepi
103
How is epinephrine or norepinephrine terminated in the synapse?
* **Reuptake**
* Alpha2 (an autoreceptor) senses concentration and signals for reuptake
* **Diffusion**
* **Metabolism**
104
What are the agonists and antagonists to adernergic receptors?
* Agonists: NE, EPI
* Antagonists: Proponolol (B1/B2 nonspecific blocker)
105
What are the functions of alpha1 receptors and where do they act on?
**Functions**
* Gq pathway
* Increases Intracellular Ca2+
* Vasoconstriction (BP) increases
**Acts On**
* On smooth muscle of vessels, eye, and GI/urinary sphincters
* smooth muscle contraction by stimulating phospholipase C and Ca2+
106
What are the functions of alpha2 receptors and where do they act on?
**Functions**
* Gi
* Decreases cAMP (through adenyl cyclase)
* Decreases norepinephrine release (autoreceptor) by hyperpolarizing the cell
**Acts On**
* Presynaptic nerve terminals
107
What are the functions of beta1 receptors and where do they act on?
**Function**
* Gs
* Increases HR
* Increases contractility
**Acts On**
* Heart
108
What are the functions of beta2 receptors and where do they act on?
**Function**
* Gs
* coupled to Gproteins → increases adenylyl cyclase and cAMP → phosphorylation of myosin light chain kinase → blocks function and decreases contraction
**Acts On**
* located on most tissues (can be innervated or noninnervated)
* Activation leads to relaxation of smooth muscle (uterus, GI, bladder)
109
What are the functions of beta3 receptors and where do they act on?
**Function**
* Gs
* increases lipolysis
**Acts On**
* adipocytes
110
How is acetyl cholinesterase broken down?
* Serine attaches to the ester site → breaks down into acetate and acetylcholinesterase
111
What is the therapeutic function of acetyl cholinesterase inhibiton? Name a disease associated with the neuromuscular junction.
* Therapeutically, acetyl cholinesterase inhibition allows for ACh to remain in synapse to stimulate receptors
* Conversely, lack of acetyl cholinesterase can cause overstimulation of ACh (insecticides and WMDs target acetyl cholinesterase)
* Myasthenia Gravis: lack of ACh postsynaptic receptors causes a reduction in depolarization and therefore muscle weakness
112
What is meant by the natural tension between innervated and non-innervated receptors and the potential therapeutic use(s) of that tension?
Since there are more beta 2 receptors than innervated alpha 1 receptors (vasoconstriction) in non-innervated tissues like the smooth muscle of blood vessels, epinephrine release into blood stream will cause vasodialation.
SPM
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