1
Q
what is the human proteome
A
represents full number of proteins that are expressed by all the hereditary information in our DNA, also referred to as the genome
- 20-25,000 protein encoding genes
- great complexity due to RNA processing and post-translational modifications
2
Q
what contributes to the complexity of the proteome
A
alternative splicing and post-translational modifications
3
Q
when can the composition of our proteome change
A
in response to various factors
- can include an organism’s developmental stage and especially in response to internal and external signals
4
Q
How do cells interact with their environment?
A
- detect changes in their environment through various mechanisms
- these changes act as stimuli that trigger specific cellular responses
5
Q
What is a stimulus in a biological context?
A
A stimulus is any change in the environment that can be detected by cells and leads to a physiological response
6
Q
Give an example of a stimulus related to eating
A
Eating a meal causes an increase in blood glucose levels, which acts as a stimulus for certain cells in the body
7
Q
Why is blood glucose regulation important?
A
Blood glucose levels must be regulated to maintain homeostasis and ensure proper cellular function
8
Q
Which cells are responsible for detecting changes in blood glucose levels?
A
Specialized beta islet cells in the pancreas detect changes in blood glucose levels
9
Q
What happens when beta cells detect high blood glucose levels?
A
They trigger a series of events that work to return blood glucose levels to normal
10
Q
How does the pancreas respond to high blood glucose?
A
The pancreas increases the synthesis and secretion of insulin, a protein hormone
11
Q
What is insulin?
A
Insulin is a protein effector hormone produced by pancreatic beta cells that helps regulate blood glucose levels
12
Q
What is meant by an “effector protein”?
A
a molecule that produces a response in target cells after being released in response to a stimulus
13
Q
What is the role of insulin in the body?
A
communicates with target cells to promote glucose uptake, thereby lowering blood glucose levels
14
Q
What happens to glucose after eating a meal?
A
Glucose is absorbed into the bloodstream from the digestive system
15
Q
Where can some glucose absorption occur besides the intestines?
A
A small amount of glucose can be absorbed in the mouth across thin epithelial surfaces with underlying capillaries
16
Q
Where does most glucose absorption occur?
A
Most glucose absorption occurs in the microvilli cells of the small intestine
17
Q
What are microvilli and why are they important?
A
Microvilli are tiny projections in the small intestine that increase surface area, allowing for efficient nutrient absorption, including glucose
18
Q
How is glucose transported after absorption in the small intestine?
A
Glucose is absorbed into nearby small blood vessels (capillaries) and then transported through the bloodstream
19
Q
What system transports glucose throughout the body?
A
The circulatory system carries glucose to cells throughout the body
20
Q
How do pancreatic beta cells respond after glucose enters the bloodstream?
A
They detect increased glucose levels and adjust insulin production and secretion accordingly
21
Q
What is the overall effect of insulin release after a meal?
A
Insulin acts to reduce blood glucose levels, bringing them back to normal
22
Q
At what levels is insulin biosynthesis regulated?
A
at both the transcriptional level (gene → mRNA) and the translational level (mRNA → protein)
23
Q
What biological process stimulates insulin production at the molecular level?
A
Glucose metabolism stimulates insulin production by increasing both:
- Insulin gene transcription
- mRNA translation
24
Q
Where is insulin protein synthesized in pancreatic cells?
A
in the rough endoplasmic reticulum (RER) of pancreatic beta cells
25
What is the initial length of the insulin polypeptide produced from the insulin gene?
The insulin gene codes for a polypeptide that is 110 amino acids long
26
Is the initially translated insulin polypeptide the same as the functional insulin protein?
No
27
What is the length of the functional insulin protein that is secreted?
The functional insulin protein consists of 51 amino acids
28
Why is there a difference between the 110 amino acid polypeptide and the 51 amino acid functional insulin?
because the initial polypeptide undergoes post-translational modifications, which process it into the final functional form
29
Who determined the structure of insulin and by what method?
Dorothy Hodgkin determined the structure of insulin using X-ray crystallography
30
What is the structural composition of functional insulin?
Functional insulin consists of two polypeptide chains:
- alpha chain with 21 amino acids
- beta chain with 30 amino acids
31
How do the two insulin chains combine to form the functional protein?
The alpha (21 aa) and beta (30 aa) chains associate together to form a dimer, which makes up the functional insulin protein
32
What does “dimer” mean in the context of insulin?
A dimer is a structure formed when two polypeptide chains bind together to create a functional protein
33
How is the 110 amino acid polypeptide converted into the two-chain insulin structure?
It is processed through post-translational modifications, which:
- Cut (cleave) the original polypeptide
- Reorganize it into two separate chains (21 aa and 30 aa)
34
What are post-translational modifications?
changes made to a protein after translation, such as cleavage and structural rearrangement, to produce the final functional form
35
Summarize the full process of insulin biosynthesis.
1. Glucose metabolism increases insulin gene transcription
2. mRNA is translated in the rough ER
3. A 110 amino acid polypeptide is produced
4. The polypeptide undergoes post-translational modifications
5. It is cleaved into two chains (21 aa and 30 aa)
6. The chains combine to form a functional 51 amino acid insulin protein (dimer)
7. Functional insulin is secreted from pancreatic beta cells
36
What does the insulin gene encode?
a 110 amino acid precursor protein called preproinsulin, which is the initial form of insulin before processing
37
What is preproinsulin?
the inactive precursor of insulin that contains additional sequences required for proper processing and targeting within the cell
38
What special feature does preproinsulin contain at its N-terminus?
an N-terminal signal sequence, which directs the protein to the rough endoplasmic reticulum (RER)
39
What is the role of the signal recognition particle (SRP)?
it binds to the N-terminal signal sequence and facilitates the translocation of preproinsulin into the lumen of the rough ER
40
What happens to preproinsulin once it enters the rough ER?
The signal sequence is cleaved off, converting preproinsulin into proinsulin
41
What is proinsulin?
an intermediate form of insulin produced after removal of the signal sequence from preproinsulin
42
What types of processes convert proinsulin into mature insulin?
undergoes post-translational modifications, including folding, bond formation, and cleavage, to become mature insulin
43
What structural changes occur to proinsulin during folding
Proinsulin undergoes:
- Protein folding
- Formation of three disulfide bonds
44
What are disulfide bonds and why are they important?
covalent bonds between sulfur atoms of cysteine residues that help stabilize the 3D structure of the protein
45
What assists in the proper folding of proinsulin?
Chaperone proteins in the rough ER
46
What happens to proinsulin after folding in the rough ER?
The folded proinsulin is transported from the rough ER to the Golgi apparatus for further processing
47
What occurs in the Golgi apparatus during insulin maturation?
Further cleavage of proinsulin occurs, producing a mature insulin dimer containing:
- The mature insulin protein (A and B chains)
- A small connecting peptide (C chain) that is released
48
What is the C chain (C peptide)?
a small peptide that is removed during insulin maturation and released as a byproduct
49
What is the final structure of mature insulin?
Mature insulin is a dimer composed of two chains:
- A chain
- B chain
50
Why are post-translational modifications essential for insulin function?
They ensure that the N-terminal and C-terminal regions of the A and B chains are correctly formed so insulin can bind to insulin receptors on target cells
51
What are some types of post-translational modifications besides cleavage?
Folding
Disulfide bond formation
Covalent attachment of molecules
Protein degradation
52
What does “covalent attachment” mean in protein modification?
the addition of chemical groups to proteins through covalent bonds, altering their function or activity
- ex: phosphorylation, methylation, acetylation
53
What is phosphorylation?
the covalent attachment of a phosphate group to Serine, Threonine, and Tyrosine residues in a protein
- carried out by enzymes called KINASES
54
what is methylation
the covalent attachment of a methyl group to a protein
55
what is acetylation
the addition of an acetyl group to a specific amino acid residue in a protein
56
Summarize the full process from preproinsulin to mature insulin.
1. Insulin gene produces preproinsulin (110 aa)
2. N-terminal signal sequence directs it to the rough ER via SRP
3. Signal sequence is cleaved → proinsulin
4. Proinsulin folds and forms 3 disulfide bonds (with chaperones)
5. Moves to Golgi apparatus
6. Further cleavage removes C chain
7. Mature insulin (A + B chains) is formed
8. Functional insulin is secreted
57
What happens after pancreatic beta cells release insulin?
Released insulin molecules bind to receptors on specific target tissues, initiating cellular responses
58
What are receptors?
proteins that receive and interpret signals from signalling molecules (ligands), such as insulin
59
How many types of cellular receptors exist and what is their function?
there are thousands of different receptors, each capable of:
- Binding specific signals (ligands)
- Producing a specific intracellular response
60
What type of receptor does insulin bind to?
Insulin binds to insulin receptors, which belong to the family of receptor kinases
61
What is the main effect of insulin binding to its receptor?
enables cells to transport glucose across the plasma membrane into the cytosol, lowering blood glucose levels
62
In what form do receptor kinases exist before activation?
as monomers (single units) before binding to a signal
63
What happens when insulin binds to receptor kinase monomers?
Binding causes a conformational change, leading the receptor monomers to pair up (dimerize)
64
What is receptor dimerization?
the process where two receptor monomers join together to form an active complex
65
What happens after receptor dimerization?
The cytoplasmic domains of the receptors become activated and gain kinase activity (they act like kinase proteins)
66
What is the role of kinase proteins?
phosphorylate specific amino acids on proteins, modifying their activity
67
What happens during receptor autophosphorylation?
The receptor kinase domains phosphorylate each other at many regions on the receptor tails
68
What is the result of receptor autophosphorylation?
creates binding sites for other proteins, leading to their activation and continuation of the signalling pathway
69
What is intracellular signal amplification?
the process where a single extracellular signal (insulin) triggers a cascade of multiple intracellular activations, greatly increasing the response
70
What is the final outcome of the insulin signalling pathway inside the cell?
Activation of glucose transporter proteins at the cell surface, leading to glucose uptake into the cell
71
what sequence of events occurs after insulin binds its receptor?
1. Insulin binds receptor
2. Receptor undergoes conformational change
3. Receptors dimerize
4. Autophosphorylation occurs
5. Cytoplasmic proteins are activated
6. Signal cascade continues
7. Glucose transporters are activated
8. Glucose enters the cell
72
What types of proteins are involved downstream of the receptor?
Transducer and amplifier proteins, which help relay and strengthen the signal
73
What is the role of transducer proteins?
They transmit the signal from the receptor to other intracellular components
74
What is the role of amplifier proteins?
They increase the strength of the signal, allowing a small initial signal to produce a large response
75
How is the initiation and maintenance of a signalling pathway regulated?
Through positive feedback loops, which help sustain and amplify the signal
76
What is positive feedback in signalling pathways?
A mechanism where the output of a pathway enhances or reinforces the signal, keeping it active
77
How can signalling pathways be turned off?
Through negative feedback loops, which reduce or terminate the signal
78
What is negative feedback in signalling?
A process where components of the pathway inhibit further signalling, leading to signal termination
79
What is double negative feedback?
occurs when an inhibitor of a signal is itself inhibited, effectively enhancing the signal
- provides fine control over cellular responses to extracellular signals
80
What is the role of tissues with insulin receptor kinases?
can detect changes in blood glucose levels and contribute to glucose uptake from the blood
81
What do fat (adipose) cells do with glucose and fatty acids
Take up glucose and fatty acids & store excess as triglycerides (fat storage form)
82
How do liver and muscle cells handle excess glucose?
Take up glucose from the blood & store excess glucose as glycogen
83
Do all tissues absorb glucose equally?
No; some are more efficient than others
- ex. Skeletal muscle cells absorb glucose more efficiently than liver cells
84
How do eukaryotic cells increase protein diversity from a single gene?
By regulating mRNA processing, allowing multiple mRNA transcripts to be produced from one gene
85
What is the significance of producing multiple mRNA transcripts from one gene?
allows a single gene to code for multiple protein products, increasing proteomic complexity
86
What is alternative splicing?
a single pre-mRNA is spliced at different junctions, producing different mature mRNA molecules with different exon combinations
- allows one gene to produce multiple mRNA transcripts
87
What are mRNA isoforms?
Different versions of mature mRNA produced from the same pre-mRNA due to alternative splicing
88
Why does alternative splicing occur at the molecular level?
Because the spliceosome may recognize sequences differently, identifying a region as an exon in one transcript but as an intron in another
89
How does alternative splicing regulate gene expression
allows the same primary transcript to produce different mRNA isoforms, leading to different but related proteins
90
How many exons are in the human insulin receptor gene?
22
91
What happens to exon 11 in skeletal muscle cells?
Exon 11 is removed during splicing along with introns and the mRNA isoform will then be translated into a higher affinity version
92
What type of insulin receptor is produced in skeletal muscle cells?
A higher-affinity insulin receptor isoform
93
What is the functional result of a high-affinity insulin receptor in muscle cells?
Muscle cells can respond more strongly to insulin & increase glucose uptake
94
Why is a high-affinity insulin receptor beneficial in skeletal muscle?
Because muscle cells help lower blood glucose levels & require high energy, so they need efficient glucose uptake
95
What happens to exon 11 in liver cells?
Exon 11 is retained in the mature mRNA
96
What type of insulin receptor is produced in liver cells?
A lower-affinity insulin receptor isoform
97
Why do liver cells have lower insulin receptor affinity?
Because exon 11 is included, altering the receptor structure and reducing insulin binding affinity
98
What is the genome composed of?
4 nucleotides and is identical in all cells
99
How do proteins differ despite identical DNA?
due to the production of different isoforms
100
What happens if alternative splicing or post-translational modifications are disrupted?
can lead to detrimental cellular effects
101
What happens if insulin is not properly processed after translation?
may fail to bind to insulin receptors, preventing its function
102
What happens if the insulin receptor is incorrectly spliced?
It may be unable to activate glucose transporter proteins & enable glucose uptake into cells
103
What is the consequence of defective insulin or insulin receptors?
- Inability to take up glucose
- Leads to hyperglycemia (high blood sugar)
- Can result in diabetes
104
what are wild-type characteristics
- grows on minimal medium
- able to make all the amino acids & other substances that it requires to survive
105
what holds the mussels to the rock
fibers --> proteins secreted by the muscular foot of the mussel
106
what do the mussel proteins have
keratin and a resinous protein and other proteins which form a strong, tough adhesive called BYSSUS
107
why do genetic engineers insert segments of mussels DNA into yeast cells
serve as factories, translating mussel genes into byssus
108
what happens if the mussels are exposed to high temp or acidic conditions
their proteins denature and they lose grip (get preyed on)
109
what is the kermode spirit bear
- a white subspecies of the American black bear
- a single nucleotide mutation results in a modified protein product from the mc1r gene
110
who discovered the truth behind kermode spirit bear
- Kermit Ritland & coworkers
- they identified single nucleotide mutation in the melanocortin 1 receptor gene (mc1r) which caused a tyrosine to cysteine replacement at codon 298
- the mc1r gene encodes for a protein responsible for regulation skin and hair colour
111
eden atwood: what is androgen insensitivity?
- a mutation that changes the nucleotide sequence of a single gene, causing a defective protein to be produced
- causes a person who is genetically male (XY) to look like a female
- no functional androgen receptor proteins, so cells are unable to respond to testosterone
- female is carrier & genetically inherited by recessive gene
112
is LacI housekeeping or regulatory?
housekeeping gene --> expressed all the time
BIO 1AO3
flashcards
Decks in class (20)
# Cards
-
composition and structure of membranes42
-
organelles and energy23
-
proteins50
-
nucleic acids31
-
transcription53
-
genetic code20
-
translation34
-
complex proteome112
-
modulating transcription46
-
prokaryotic transcription regulation80
-
eukaryotic transcription regulation96
-
turning off the signal91
-
the cell cycle81
-
replication60
-
applications of DNA replication89
-
DNA mutations71
-
meiosis58
-
genetic variation72
-
sex chromosomes and linkage68
-
principles of inheritance56
