SM162 Intermediary Metabolism I

Question 1

Catabolism vs. Anabolism

Answer 1

Catabolism: breakdown, extract energy

Anabolism: synthesis

Question 2

3 cellular fates of glucose

Answer 2

Glycolysis

Glycogenesis

Pentose phosphate pathway

Question 3

What happens to glucose when it enters the cell? Why? What enzyme does this?

Answer 3

Gets phosphorylated

Traps the molecule within the cell

Hexokinase (yield glucose-6-phosphate)

Question 4

Rate-limiting enzyme in glycolysis

Answer 4

Phosphofructokinase-1 (PFK-1)

This is the irreversible committment step for entry of G6P into glycolysis

Question 5

Overall glycolysis reaction

Answer 5

Glucose + 2 NAD + 2 Pi + 2 ADP –>
2 pyruvate + 2 NADH + 4 H+ + 2 ATP + 2 H2O

Question 6

Glycolysis pathway

Answer 6

Question 7

Glyceraldehyde 3-phosphate dehydrogenase actions

Answer 7

Oxidizes glyceraldehyde-3-P (G3P) and transfers electrons to NAD to form NADH

Question 8

Glycolysis steps that directly generate ATP (name the enzymes)

Answer 8

Phosphoglycerate kinase and pyruvate kinase

Question 9

Regeneration of NAD

Answer 9

Needed to continue glycolysis

Anaerobic: lactic acid pathway - convert pyruvate to lactate and NAD (lactate dehydrogenase)

Aerobic: NAD is regenerated in the TCA cycle

Question 10

Aerobic vs. anaerobic glycolysis yield

Answer 10

Aerobic: 30-32 ATP/glucose

Anaerobic: 2 ATP/glucose

Question 11

3 key regulation steps in glycolysis

Answer 11

1) hexokinase, 2) PFK-1, 3) pyruvate kinase

Question 12

Hexokinase regulation

Answer 12

Inhibited by G6P (its product)

Low Km in most tissues except liver (high Km ensures G6P is available for energy storage)

Question 13

PFK-1 regulation

Answer 13

Allosteric regulation

Inhibitory: ATP and citrate

Stimulatory: AMP and fructose-2,6-bisP

Question 14

Fructose 2,6-bisP, PFK-2, and PFK-1 regulation

Answer 14

F2,6-bisP regulates PFK-1

Not generated in glycolysis, instead controlled by the bifunctional kinase/phosphatase PFK-2 that is in turn under the control of PKA

Liver: fasting causes glucagon release and cAMP-dependent PKA activity, which phosphorylates PFK-2, leading to less F2,6-bisP and less glycolysis

Heart: adrenergic stimulus or more AMP -> more F2,6-bisP -> more glycolysis

Question 15

Pyruvate kinase regulation

Answer 15

Tissue-specific isoenzymes including R (red cells), L (liver), M1/M2 (muscle)

L form has allosteric sites. Activation: fructose 1,6-bisP, inhibition: ATP. Can also be non-allosterically blocked by PKA phosphorylation

Question 16

Pentose phosphate pathway

Answer 16

Produces ribose-5-P to synthesize nucleotides

Generates NADPH from NADP for fatty acid and steroid biosynthesis and to prevent oxidative damage through reduced glutathione in RBCs

Converts pentoses to hexoses, which go on to become nucleotides or reenter glycolysis

High activity in the adrenals, liver, and mammary gland

Question 17

Glucose 6-phosphate dehydrogenase: pathway, importance, regulation, chromosome type

Answer 17

Part of the PPP

Rate-limiting step

Regulated by NADP/NADPH ratio

X-linked gene

Question 18

Glucose 6-phosphate dehydrogenase deficiency

Answer 18

Inherited deficiency leads to hemolytic anemia in the setting of oxidizing drugs or diets

Oxidizing drugs/diet includes fava beans, sulfa antibiotics, Tb drugs, and malaria drugs

Most important in the RBCs

Question 19

Gluconeogenesis starting materals

Answer 19

Can use glycerol, alpha-keto acids, or lactate

Question 20

Gluconeogenesis: role during fasting, locations in the body

Answer 20

Sole source of glucose

Liver, kidneys, intestinal epithelium

Question 21

Gluconeogenesis: differences from glycolysis

Answer 21

Differs at the 3 irreversible steps of glycolysis (hexokinase, PFK-1, pyruvate kinase)

Question 22

Gluconeogenesis: role of ATP and citrate

Answer 22

Products of glycolysis, indicate that energy production is high

Feedback and shut off glycolysis

Question 23

Overall gluconeogenesis reaction

Answer 23

2 Pyruvate + 6 ATP + 2NADH + 2H+ + 2H2Oàglucose + 6 ADP + 6 Pi + 2 NAD+

Question 24

Fructose 1,6 bisphosphatase: pathway, reaction, regulation

Answer 24

Gluconeogenesis

Removes the phosphate group from carbon 1 of fructose 1,6-bisphosphate

Activated by citrate, inhibited by fructose 2,6-bis-P

Question 25

Glucose-6-phosphatase: pathway, reaction

Answer 25

Gluconeogenesis

Converts glucose-6-P to glucose

Question 26

Pyruvate carboxylase and PEP carboxykinase: pathway, reactions, regulation

Answer 26

Gluconeogenesis

Carry out successive reactions to turn pyruvate into oxaloacetate and then phosphoenolpyruvate (PEP)

Pyruvate carboxylase is activated by acetyl CoA

Question 27

Gluconeogenesis pathway

Answer 27

Question 28

Glycogenesis: describe steps, which is the most important regulation point?

Answer 28

G6P converted to G1P by phosphoglucomutase

G1P reacts with UTP to form UDP-glucose

UDP-glucose gets add in an alpha-1,4 linkage to glycogen polymer by glycogen synthase (regulated step)

When chains reach ~11 residues in length, alpha-1,4 glucose oligos are removed by branching enzyme and reattahced to make alpha-1,6 bonds

Question 29

How many ATP are used in glycogenesis for each molecule of glucose?

Answer 29

2

Question 30

What happens to glycogen if you have no branching enzyme?

Answer 30

Long glucose polymers with no branches and lots of alpha-1,4 linkages

Question 31

Continue with glycogenolysis

Answer 31

Continue with glycogenolysis