E3 Module 7

Question 1

Can enzyme regulation be stimulatory inhibitory or both?
What are the results of this?

Answer 1

Enzyme regulation could be stimulatory, resulting in an overall increase in enzyme activity, or it could be inhibitory, resulting in a decrease in enzyme activity.

Question 2

Enzyme regulation is mediated by:

Answer 2

• bioavailability of enzymes in different tissues and cellular compartments
  -control of catalytic efficiency through binding of regulatory molecules
  -covalent modification
  -proteolytic processing

Question 3

What type of control of enzyme activity often involves the binding of small molecules (metabolites) to regulatory sites on the enzyme located outside of the active site?

Answer 3

allosteric

Question 4

Name the processes affecting enzyme bioavailability

Answer 4

RNA synthesis, processing, protein synthesis, protein degradation, and protein targeting.

Question 5

What is catalytic efficiency regulated by

Answer 5

inhibition, allosteric control, covalent modification, and proteolytic processing

Question 6

Enzymes are subject to ____________ _____________ due to noncovalent binding of small molecules, and _______________ ______________, in which the inhibitory molecule forms a covalent bond in the enzyme active site

Answer 6

reversible inhibition
irreversible inhibition

Question 7

What are the three classes of reversible inhibitors?

Answer 7

Competitive inhibitors, uncompetitive inhibitors, and mixed inhibitors.

Question 8

With increasing concentration of a competitive inhibitor, the apparent ______ of the enzyme increases, reflecting the requirement of higher substrate concentration to reach ________, however, not the _______

Answer 8

competitive inhibitior
Km
1/2 Vmax
not Vmax

Question 9

Competitive inhibition is characterized by

Answer 9

inhibitors that bind to the free enzyme and inhibit substrate binding at the active site

Question 10

Uncompetitive inhibitors decrease both the ______ and apparent ____ kinetic parameters by the same factor; uncompetitive inhibition is/is not overcome by increasing substrate concentration

Answer 10

Vmax and Km decrease
is not overcome by increasing substrate concentration

Question 11

Mixed inhibitors are similar to ____________ inhibiotrs in that they bind to sites distinct from the active site. The difference is that mixed inhibitors can bind to both ____________ and ______________. _________________ is a rare case of mixed inhibition.

Answer 11

uncompetitive
enzyme and the enzyme substrate complex
Noncompetitive inhibition

Question 12

What prevents hydrated Na+ and K+ ions from passing through the nicotinic acetylcholine receptor channel in the absence of acetylcholine?

Answer 12

A ring of nonpolar amino acids in the interior chamber prevents the hydrated ions from moving through the constricted channel.

Question 13

name the functional component of the receptor type: nicotinic acetylcholine receptor

Answer 13

opening of the inner chamber to facilitate ion transport

Question 14

name the functional component of the receptor type: receptor tyrosine kinase

Answer 14

autophosphorylation of the cytoplasmic tail and binding of adaptor proteins to Tyr-P

Question 15

name the functional component of the receptor type: nuclear receptor

Answer 15

transcriptional regulation of downstream target genes

Question 16

name the functional component of the receptor type: G-protein coupled receptor

Answer 16

GDP-GTP exchange and dissociation of the heterotrimeric G protein

Question 17

name the functional component of the receptor type: Tumor necrosis factor receptor

Answer 17

assembly of adaptor complexes through TNF receptor-associated death domain proteins

Question 18

describe the 8 steps of signaling events showing how glucagon binding to glucagon receptors in liver cells increases blood glucose levels in between meals.

Answer 18

1. Glucagon binds to the N-terminal
2. The C-terminal domain undergoes a conformational change
3. The GDP bound heterotrimeric G protein binds to the receptor
4. GDP is exchanged for GTP in the G-alpha subunit
5. The G alpha and G beta/gamma subunits dissociate
6. the G alpha subunit binds to activate adenylate cyclase
7. Production of cyclic AMP leads to activation of PKA
8. PKA phosphorylates downstream proteins that control glucose transport.

Question 19

Based on the Butowt, R. and von Bartheld, C.S. (2020) paper:

a) what might explain why ~60% of COVID-19 patients do not experience anosmia even though they experience other symptoms of SARS-CoV-2 infection?

b) what might explain why ~10% of COVID-19 patients with anosmia do not regain their sense of smell even after 3 months?

Answer 19

a) The olfactory support cells were not infected and/or killed by the virus.

b) The stem cells needed to replenish olfactory support cells were killed.

Question 20

LO - Differentiate between the three classes of reversible inhibitors

Question 21

LO - recognize the difference between the kinetics of reversible inhibitors using Lineweaver–Burk plots

Answer 21

Question 22

LO - Identify the roles of ATP and CTP in the regulation of aspartate transcarbamoylase (ATCase)

Answer 22

ATP - shifts line in V0 vs substrate concentration graph to the left, stimulates ATCase activity
CTP - shifts line to the right, inhibits ATCase activity

Question 23

What happens when ATP binds to the regulatory subunit of an enzyme in comparison to CTP?

Answer 23

When ATP binds to the subunit of the enzyme, it shifts ATCase to the activated R state, whereas CTP binding to the regulatory subunit stabilizes the inactive T state conformation.

Question 24

LO - the role of allosteric regulation and covalent modification in ATCase activity

Answer 24

covalent modification
-phosphorylation
-adenylylation
-uridylylation

Question 25

In the unphosporylated T state conformation, is glycogen phosphorylase active or inactive? What about the R state

Answer 25

inactive in T state, active in R state

Question 26

What happens during the most common form of covalent modification of enzymes, phosphorylation of Ser, Thr, Tyr residues by kinase enzymes

Answer 26

it adds a negative charge to the enzyme through the addition of inorganic phosphate (PO3^2-)

Question 27

Regulation of enzyme activity by proteolytic cleavage is by its very nature an…

Answer 27

irreversible process

Question 28

LO - Define the components of a cell signaling pathway

Answer 28

receptor protein - activated and leads to the modification of intracellular target proteins
target proteins - intracellular, control a variety of cellular responses
first messengers
upstream and downstream signaling proteins
second messengers

Question 29

LO - the difference between first and second messengers

Answer 29

first messengers - not all peptide hormones, some are lipids and steroids, and others are even smaller like nitric oxide, Ca2+, and CO2-

second messengers - signal amplification, involves enzymes that catalytically activate downstream signaling proteins, many of which are also enzymes cyclic AMP

Question 30

LO - Compare G-protein coupled receptors, receptor tyrosine kinases, and ligand-gated ion channels

Question 31

LO - Distinguish between the shared pathways and parallel pathways of glucagon and epinephrine activity

Question 32

LO - Explain the differences between the GDP-bound and GTP-bound states of the G subunit

Question 33

LO - identify key steps in protein kinase A activation

Question 34

LO - guanine nucleotide exchange factor

Question 35

LO - GTPase activating protein

Question 36

LO - G protein receptor kinase

Question 37

LO - adrenergic receptor kinase

Question 38

LO - arrestin

Question 39

low Kd = _______ affinity
high Kd = _______ affinity

Answer 39

high
low

Question 40

describe best case scenario for inhibitor development

Answer 40

low Kd, competitive inhibitor

Question 41

A phosphodiesterase inhibitor will prevent degradation of ________ to __________.

Answer 41

cAMP to AMP

Question 42

Adenylate cyclase is the enzyme that converts _____ to _______.

Answer 42

ATP to cAMP

Question 43

How does addition of CTP effect ATCase activity?

Answer 43

inhibits ATCase activity
moves graph to the right

Question 44

How does addition of ATP affect ATCase activity

Answer 44

stimulates ATCase activity
moves graph to the left

Question 45

cGMP is a ________ messenger for vasodilation. Increased NO leads to ________ cGMP, which activates protein kinase G. Sildenafil, or Viagra, prolongs vasodilation by _________ cGMP phosphodiesterase. cGMP phosphodiesterase _______ cGMP and ________ vasodilation. By inhibiting this enzyme, the concentration cGMP remains _________ and vasodilation is prolonged.

Answer 45

cGMP is a secondary messenger for vasodilation. Increased NO leads to increased cGMP, which activates protein kinase G. Sildenafil, or Viagra, prolongs vasodilation by inhibiting cGMP phosphodiesterase. cGMP phosphodiesterase degrades cGMP and decreases vasodilation. By inhibiting this enzyme, the concentration cGMP remains higher and vasodilation is prolonged.