Control of Glycolysis

Question 1

Which 3 enzymes in glycolysis operate far from equilibrium?

Answer 1

1) Hexokinase
2) Phosphofructokinase
3) Pyruvate kinase

Question 2

Which enzymes in metabolic pathways are potential sites of control in the pathways?

Answer 2

Those that catalyze essentially irreversible reactions.

Question 3

Which enzymes in glycolysis catalyze irreversible reactions and are, therefore, potential sites of control in the glycolysis pathway?

Answer 3

1) Hexokinase
2) Phosphofructokinase
3) Pyruvate kinase

Question 4

Under what conditions does glycolysis operate continuously in most tissues?

Answer 4

Steady state conditions

Question 5

What allows control of irreversible reactions (and, therefore, control of the pathway) in metabolic pathways?

Answer 5

1) Reversible binding of allosteric effectors

2) Covalent modification

Question 6

Which enzymes in glycolysis are regulated simply based on relative concentrations of substrate and product?

Answer 6

All that are reversible (7 of the 10)

Question 7

In what ways is phosphofructokinase like hemoglobin?

Answer 7

It is a tetramer with R and T conformations

Question 8

Which enzyme is the most important regulatory enzyme in glycolysis?

Answer 8

Phosphofructokinase

Question 9

Is phosphofructokinase a more important enzyme in liver or in muscle?

Answer 9

In muscle

Question 10

Which molecule inhibits phosphofructokinase? What kind of inhibitor is it?

Answer 10

ATP; allosteric

Question 11

What molecules reverse the inhibitory effect of ATP on phosphofructokinase and activate the enzyme?

Answer 11

AMP, ADP, and fructose 2, 6 phosphate (book says only AMP—???)

Question 12

True or false: ATP functions as both a substrate and an inhibitor for phosphofructokinase?

Answer 12

True

Question 13

How does a decrease in pH affect the activity of phosphofructokinase? Why?

Answer 13

It inhibits it. The pH would drop when lactic acid builds up as the muscle functions anaerobically; the inhibition of ATP protects the muscle from damage due to continuing anaerobic activity.

Question 14

Which site or sites on phosphofructokinase can bind ATP in either the R or T state?

Answer 14

Only the substrate site

Question 15

Which site or sites on phosphofructokinase can bind ATP only in the T state?

Answer 15

The inhibitor site

Question 16

Which state must phosphofructokinase be in to bind fructose-6-phosphate?

Answer 16

The R state

Question 17

How does the binding of ATP during time of high concentration of ATP affect the conformation of phosphofructokinase?

Answer 17

ATP binds to the inhibitor site, shifting the RT equilibrium to the T state.

Question 18

How does an increase in concentration of ATP affect the curve of the graph of PFK activity vs. concentration of F6P?

Answer 18

It makes the curve more sigmoidal, shifting it to the right (KM is increased).

Question 19

How does an increase in concentration of AMP affect the curve of the graph of PFK activity vs. concentration of F6P?

Answer 19

It shifts the curve to the left, making it less sigmoidal (KM is decreased)

Question 20

When is PFK near max activity?

Answer 20

When there is a low concentration of ATP or no inhibitors

Question 21

Why does an increased concentration of AMP shift the binding curve of PFK to the left?

Answer 21

Binds to the R state PFK, shifting the TR equilibrium toward R.

Question 22

True or false: Direct allosteric control of PFK by ATP appears to be all that’s needed to control glycolysis flux. Why?

Answer 22

False; because flux through glycolysis varies by 100x or more, while concentration of ATP only varies by +/- 10%.

Question 23

What causes the concentration of ATP to not vary more than +/- 10%?

Answer 23

The buffering activity of two enzymes: 1) creatine kinase and 2) adenylate kinase.

Question 24

How does creatine kinase work as a buffer?

Answer 24

Catalyzes the equilibrium reaction between ATP + creatine creatine-P + ADP

Question 25

How does adenylate kinase work as a buffer for ATP concentration?

Answer 25

Catalyzes the equilibrium reaction of 2 ADP ATP + AMP

Question 26

Where does most of the ADP in muscle come from?

Answer 26

ATP hydrolysis during muscle contractions

Question 27

What is the relative concentration of ATP to ADP and AMP in muscle?

Answer 27

[ATP]= 50x[AMP] and 10x[ADP]

Question 28

What does a 10% decrease in ATP affect AMP and ADP due to the affects of adenylate cyclase?

Answer 28

100% increase in ADP and 400% increase in AMP

Question 29

How can a forward and reverse reaction both be favorable?

Answer 29

They must each be catalyzed by a different enzyme.

Question 30

True or false: it is possible for both a forward and reverse reaction to be catalyzed by a single enzyme and both be favorable simultaneously.

Answer 30

False

Question 31

What enzyme catalyzes the reverse reaction of the glycolysis step catalyzed by phosphofructokinase?

Answer 31

Fructose-1,6-bisphosphatase

Question 32

What price does muscle pay for being able to switch from resting to maximum activity quickly?

Answer 32

Substrate cycling (which uses 1 molecule of ATP every time the cycle is used)

Question 33

What are two ways that muscle produces body heat?

Answer 33

1) Thermogenesis through substrate cycling

2) Shivering

Question 34

How is non-shivering thermogenesis produced?

Answer 34

By substrate cycling in liver and muscle

Question 35

What stimulates non-shivering thermogenesis?

Answer 35

Thyroid hormone

Question 36

Why do chronically obese people tend to have lower metabolic rates?

Answer 36

They have lower rates of non-shivering thermogenesis (from substrate cycling) due to lower thyroid production.