Module 7: V4 - V6

Question 1

What are the recurring motifs in regulation?

Answer 1

compartmentalisation: where do the reactions occur?
allosteric regulation: enzymes catalysing committed and usually irreversible steps
organ specialisation: compared metabolism of brain, liver, muscle and adipose
covalent regulation and enzyme levels (hormonal regulation)

Question 2

What is the definition of allosteric?

Answer 2

of or involving a change in the shape and activity of an enzyme that results from the binding of a regulatory molecule at a site other than the active site

Question 3

What are irreversible steps equivalent to?

Answer 3

control points e.g. three irreversible steps in glycolysis

Question 4

Why don’t allosteric enzymes display Michaelis-Menten kinetics?

Answer 4

this is because an allosteric enzyme can exist in either the T-state or the R-state and various factors will determine the proportion of these states

Question 5

When will allosteric enzymes display Michaelis-Menten kinetics?

Answer 5

if the T-state or R-state is isolated

Question 6

Which irreversible step of glycolysis does PFK-1 catalyse?

Answer 6

conversion of fructose-6-phosphate to fructose-1,6-biphosphate

Question 7

Which modulators are used in allosteric regulation of PFK-1?

Answer 7

ATP and citrate are allosteric inhibitors of PFK-1

AMP, ADP and F-2,6-bisP are allosteric activators of PFK-1

Question 8

Which state of an enzyme do allosteric inhibitors stabilise?

Answer 8

the T-state

Question 9

Which state of an enzyme do allosteric activators stabilise?

Answer 9

the R-state

Question 10

Where is F-2,6-BP production regulated?

Answer 10

in the liver and muscle (regulated differently between each of these locations)

Question 11

Which inhibitors are used in allosteric regulation of hexokinase?

Answer 11

by the product of the reaction it catalyses which is glucose-6-phosphate

Question 12

Which modulators are used in allosteric regulation of pyruvate kinase?

Answer 12

liver and muscle L-PK:
inhibited by ATP4- and alanine
activated by F-1,6-bisP

Question 13

What is the difference between liver and muscle pyruvate kinase?

Answer 13

liver pyruvate kinase can undergo covalent modification muscle pyruvate kinase cannot

Question 14

What is the major fuel for the human brain?

Answer 14

glucose

Question 15

When can the brain adapt to ketone bodies? When does danger occur?

Answer 15

during starvation (> 3 days)
danger occurs when [glucose] < 2.2 mM

Question 16

What is the implication of the brain lacking fuel stores?

Answer 16

relies on a constant supply of blood glucose (via GLUT3, Km ~ 1.0 mM)

Question 17

What does the brain consume at resting conditions?

Answer 17

60% of total gluconeogenesis glucose = 120 g/day

Question 18

How much glycogen is stored in muscle?

Answer 18

75% of total body glycogen

can represent 1% of muscle weight after a meal (other 25% stored in liver)

Question 19

What is the major fuel source in the resting state?

Answer 19

muscle utilises fatty acids (85% of energy)

Question 20

What does the heart muscle use in preference to glucose?

Answer 20

ketone body, acetoacetate

Question 21

How are muscle and liver metabolites connected?

Answer 21

by the Cori cycle

Question 22

Why does adipose require glucose?

Answer 22

to perform major task of synthesising and storing triacylglycerol, which is mobilised during fasting

Question 23

How much of total available energy does adipose store?

Answer 23

> 80%

Question 24

How active is adipose during starvation? What results in this level of activity?

Answer 24

highly active as decreased insulin activates hormone-sensitive lipase which breaks down TAG

Question 25

What can the liver utilise as fuel sources?

Answer 25

glucose, fatty acids, ketone bodies and amino acids

Question 26

What does the liver prefer as a fuel source?

Answer 26

ɑ-keto acids derived from the degradation of amino acids in preference to glucose

Question 27

How much of total body glycogen does the liver store?

Answer 27

1/4 of total body glycogen

Question 28

How does the liver make 200g of glucose per day?

Answer 28

via gluconeogenesis (GNG) using lactate and alanine from muscle, glycerol from adipose and glucogenic amino acids from diet

Question 29

How active is the liver during starvation?

Answer 29

highly active making glucose via GNG to maintain blood [glucose] primarily for the brain and RBCs + oxidises FAs for energy / formation of ketone bodies for the brain, heart muscle and other tissues

Question 30

What are other functions of the liver?

Answer 30

synthesises TAGs, PLs and cholesterol and secretes as VLDL for lipoprotein transport and synthesises heme (altruistic organ)

Question 31

What are the key differences between uncompetitive inhibition and allosteric regulation?

Answer 31

allosteric regulation involves modulators which bind non-covalently to the allosteric site and can result in either an ↑ or ↓ in binding to S
uncompetitive inhibition only involves molecules which ↓ binding to S + uncompetitive inhibitors can also bind irreversibly to the active binding site

Question 32

Why can’t you describe the midpoint of an allosteric kinetics curve with a Km value?

Answer 32

this is because an allosteric kinetics curve is sigmoidal, not hyperbolic

Question 33

ATP is a substrate and an allosteric inhibitor of PFK-1. How can that be and why would that be advantageous?

Answer 33

this is because ATP has a phosphate group which it can donate in enzymatic reactions
advantageous as it allows enzymes to phosphorylate molecules