Glycolysis

Question 1

Allosteric inhibition of hexokinase

Answer 1

Feedback inhibition by its product, glucose-6-phosphate

Question 2

Activity of hexokinase

Answer 2

Constitutively activated unless G6P is present. Present in all cell types at a constant amount

Question 3

Why can hexokinase not act alone?

Answer 3

It has a very high affinity for glucose and is saturated a very low concentration

Question 4

Location regulation of glucokinase

Answer 4

Transported back and forth between the cytosol and the nucleus (inactive in the nucleus)

Question 5

Feedback inhibition of glucokinase

Answer 5

Fructose 6-phosphate decreases glucokinase activity

Question 6

Two causes of increased activity in glucokinase

Answer 6

1. Presence of glucose: promotes translocation out of the nucleus
2. Presence of insulin: upregulation of gene encoding glucokinase

Question 7

Why is glucokinase needed to supplement hexokinase?

Answer 7

Has a lower affinity for glucose and is not saturated as quickly

Question 8

Major physiological activator of PFK-1

Answer 8

Fructose 2,6-bisphosphate

Question 9

What catalyzes formation of F26BP?

Answer 9

PFK2 (necessary enzyme for glycolysis that is not directly involved in the pathway)

Question 10

When is F26BP formed?

Answer 10

When glucose and insulin concentrations are high

Question 11

Mechanism for inhibition of PFK2 by glucagon and epinephrine

Answer 11

Increase the levels of cAMP, and therefore levels of PKA. Phosphorylation of PFK2 and inhibits it by covalent modification.

Question 12

Inhibitors of PFK-1

Answer 12

High levels of citrate and ATP (indirectly, glucagon and epinephrine in the liver)

Question 13

Activators of PFK-1

Answer 13

ADP/AMP and F16BP

Question 14

Where does epinephrine increase PFK1 activity?

Answer 14

In the heart; PFK2 is activated by the hormone due to switching of the hydroxyl group from the kinase domain to the phosphatase domain

Question 15

Activator of pyruvate kinase

Answer 15

Fructose 1,6-bisphosphate

Question 16

Inhibition of pyruvate kinase

Answer 16

Presence of ATP and alanine.

Glucagon and epinephrine

Question 17

Why is alanine an inhibitor of PK?

Answer 17

It increases in starvation states and is a precursor for gluconeogenesis

Question 18

How do glucagon and epinephrine cause decrease in PK activity?

Answer 18

Increase cAMP and PKA, which phosphorylates and inactivates hepatic PK

Question 19

What does phosphoprotein phosphate do?

Answer 19

Removes the phosphate that covalently modifies PK and reactivates it

Question 20

Genetic deficiency of PK can lead to ___

Answer 20

hemolytic anemia

Question 21

Why does epinephrine have different effects on the liver compared to other organ systems?

Answer 21

Other organ systems (e.g., the heart) have a preferential use for glucose compared to the liver, so the liver stops using glucose under conditions with epinephrine to let the other organs use it

Question 22

Increased insulin or decreased cAMP results in an increase in . . .

Answer 22

PFK-1
Glucokinase
PK

Question 23

Regeneration of NAD+ in anaerobic conditions

Answer 23

Conversion of pyruvate to lactate by lactate dehydrogenase

Question 24

Mitochondria-linked shuttles

Answer 24

Reducing equivalents are transferred into the mitochondria to form NADH and FADH2, which are reoxidized using the electron transport chain

Question 25

LDH isozymes

Answer 25

In the muscle (M4), pyruvate -> lactate is preferred and gives a short burst of energy
In the heart (H4), lactate -> pyruvate is preferred to push pyruvate through the TCA cycle and produce oxidative respiration and therefore more energy

Question 26

Normal serum ratio of lactate/pyruvate

Answer 26

10/1

Question 27

E1 of PDH

Answer 27

Pyruvate dehydrogenase activity (uses thiamine pyrophosphate)

Question 28

E2

Answer 28

Dihydrolipoyl transacetylase

Question 29

E3

Answer 29

Dihydrolipoyl dehydrogenase

Question 30

Steps in PDH activity

Answer 30

1. Pyruvate decarboxylation
2. Two remaining carbons are attached to TPP
3. TPP donates the acetyl group to a lipoic acid derivative
4. CoA is added

Question 31

PDH deficiency

Answer 31

Would prevent production of acetyl CoA, which would affect the heart and brain disproportionately. Causes buildup of lactic acid and -> lactic acidosis

Question 32

Arsenic poisoning

Answer 32

Limits shuttle that helps transition the lipoic acid between its oxidized and reduced form, inhibiting PDH function

Question 33

Inhibition of PDH

Answer 33

Allosteric feedback inhibition; kinase activity that phosphorylates and deactivates PDH

Question 34

Overall PDH reaction

Answer 34

Pyruvate + CoASH + NAD+ -> Acetyl-CoA + NADH + H+ + CO2

Question 35

Cofactor needed for E1

Answer 35

Thiamine (vitamin B1)

Question 36

Cofactor needed for E2

Answer 36

Pantothenate (Vitamin B5)

Question 37

Cofactor needed for E3

Answer 37

Riboflavin (B2)

Niacin (B3)

Question 38

Net production of ATP through the CAC

Answer 38

32 ATP

Question 39

Galactosemia

Answer 39

Caused by a deficiency in galactokinase or galactose 1 phosphate uridyltransferase, increasing formation of galactitol

Question 40

Which is worse: galactosemia due to galactokinase deficiency or galactose-1-phosphate uridyltransferase?

Answer 40

The latter; the galactose is already phosphorylated

Question 41

Hereditary fructose intolerance

Answer 41

Defective aldolase B cannot cleave F1P into DHAP and glyceraldehydes, so F1P builds up in the cell and depletes ATP and Pi.

Question 42

Symptoms of hereditary fructose intolerance

Answer 42

Vomiting, hypoglycemia, jaundice, and hepatic failure/cirrhosis

Question 43

Essential fructosuria

Answer 43

Lack of fructokinase; no phosphorylated sugars and they just get passed through the kidney and into urine. Benign condition