Mitsoura - Glycolysis

Question 1

Describe the sources of GLUCOSE for glycolysis and how these sources are used as a function of metabolic state

Answer 1

Dietary intake (fed state), from glycogenolysis (fasting state), from gluconeogenesis (starving state - new glucose synthhesis)

Question 2

Where is glucokinase found/located?

Answer 2

liver and pancreas only

Question 3

Glucokinase has a high Km for glucose. What does this mean?

Answer 3

It has a low affinity for glucose and therefore it has a high Vmax

Question 4

When does glucokinase work best?

Answer 4

Works best during the fed state to take in large amounts of blood glucose

Question 5

What sugars does glucokinase have an affinity for?

Answer 5

only glucose!

Question 6

Where is hexokinase found/located?

Answer 6

all tissues and organs outside liver and pancreas

Question 7

When does hexokinase work best?

Answer 7

it works at all metabolic states

Question 8

What effect does insulin have on glucokinase and hexokinase?

Answer 8

insulin has no effect on hexokinase, but glucokinase is inducible by it

Question 9

What sugars does hexokinase have an affinity for?

Answer 9

Glucose, Galactose, and Fructose

Question 10

What is the investment phase of glycolysis?

Answer 10

Step #1: Glucose → Glucose-6-Phosphate (enzyme: hexokinase/glucokinase)
Step #3: Fructose-6-Phosphate → Fructose-1,6-bisphosphate (enzyme: PFK-1)

Question 11

What is the splitting phase?

Answer 11

Step #4: Fructose-1,6-bisphosphate → Glyceraldehyde-3-Phosphate (G3P) + Dihydroxyacetone Phosphate (DHAP)
(enzyme: Aldolase A)

Question 12

How many energy generating steps are there?

Answer 12

there are 3 steps

Question 13

List the first energy generating step

Answer 13

Step #: G3P ↔ 1,3-biphosphoglycerate
(enzyme: glyceraldehyde phosphate dehydrogenase)
generates 2 NADH

Question 14

Where do the NADHs from the first energy generating step go?

Answer 14

to electron transport chain for ATP production

Question 15

List the second energy generating step

Answer 15

1,3-biphosphoglycerate ↔ 3-Phosphoglycerate
(enzyme: phosphoglycerate kinase)
generates 2 ATP

Question 16

List the third energy generating step

Answer 16

Phosphoenolpyruvate (PEP) → Pyruvate
(enzyme: pyruvate kinase)
generates 2 ATP
[this is a regulated step]

Question 17

What is the net energy generated in glycolysis

Answer 17

2 ATP and 2 NADH

Question 18

How much energy is produced anaerobically?

Answer 18

2 ATP, zero NADH

Question 19

How does insulin stimulate glycolysis?

Answer 19

by activating PFK-2, catalyzing F-6-P → F-2,6-bisphosphate, which acts as an allosteric activator of PFK-1

Question 20

How does glucagon inhibit glycolysis?

Answer 20

by activating F-2,6-bisphosphatase, catalyzing F-2,6-bisP → F-6-P, which then inhibits PFK-1

Question 21

What stimulates and inhibits glucokinase?

Answer 21

stimulation: insulin and glucose
inhibition: glucagon and ATP

Question 22

What inhibits hexokinase?

Answer 22

ATP and glucose-6-phosphate (G-6-P)

Question 23

What stimulates and inhibits phosphofructokinase-1 (PFK-1)?

Answer 23

stimulation: AMP, Insulin, Fructose-2,6-bisphosphate
inhibition: Glucagon, ATP, Citrate (TCA cycle)

Question 24

What stimulates and inhibits pyruvate kinase?

Answer 24

stimulation: Insulin, Fructose-1,6-bisphosphate
inhibition: ATP and Glucagon

Question 25

When does lactic acidosis occur?

Answer 25

it occurs when there is a build up of lactate

Question 26

What is the build up of lactate due to?

Answer 26

high concentrations of Pyruvate

Question 27

What enzyme converts Pyruvate to Lactate?

Answer 27

Lactate Dehydrogenase

Question 28

What diseases cause/result in lactic acidosis?

Answer 28

severe lung disease, Von Gierke’s (GSD), Leukemia, Metastatic carcinoma

Question 29

What two deficiencies cause/result in lactic acidosis?

Answer 29

Pyruvate dehydrogenase deficiency and α-ketoglutarate dehydrogenase deficiency

Question 30

What 6 other conditions/factors result in lactic acidosis?

Answer 30

strenuous exercise, high altitude, drowning, carbon monoxide poisoning, cyanide poisoning, and alcohol intoxication

Question 31

How does pyruvate kinase deficiency result in hemolytic anemia?

Answer 31

pyruvate kinase deficiency reduces amount of pyruvate produced, in turn reducing ATP produced via TCA cycle
structural integrity of RBCs decreases → forming acanthocytes → leading to cell lysis (aka: non-spherocytic hemolytic anemia)