22: GLUCONEOGENESIS

Question 1

gluconeogenesis introduction

Answer 1

• glycogen stores last 12-24 hours in the fasting state; must be able to synthesise glucose from other molecules
• mainly occurs in liver in mammals (universal pathway so also occurs in E.coli and plants)

Question 2

gluconeogenesis pathway

Answer 2

3 irreversible reactions in glycolysis are bypassed by enzymes in gluconeogenesis

1. pyruvate kinase - involves 2 enzymes; pyruvate to phosphoenol pyruvate; first converted to oxaloacetate
2. PFK - fru-1,6-bisP to fru-6-P simple hydrolysis reaction w/enzyme fru-1,6-bisphosphatase
3. hexokinase - glu-6-phosphatase enzyme hydrolysis P to give glu which can be released to blood

Question 2

bypassing pyruvate kinase reaction

Answer 2

-have 2 exergonic reactions

1. carboxylating pyruvate using bicarbonate to make oxaloacetate; cat by pyruvate carboxylase; biotin-dependent reaction
   - bicarbonate attached to biotin, requires ATP hydrolysis, then pyruvate comes in and bicarbonate is displaced and get addition onto pyruvate to form oxaloacetate
2. CO2 fixed by pyruvate carboxylase is released
   - no net fixation of C
   - uses GTP rather than ATP as free energy donor

Total: requires 6ATP for each glucose- costly energy process

Question 3

precursors of glucose;

where does pyruvate come from?

Answer 3

3 main sources:

• lactate
• some AAs (particularly alanine which can be converted to pyruvate in one step)
• some from glycerol released from fats; goes into gluconeogenesis as glyceraldehyde-3-P

Question 4

futile cycle

Answer 4

• if both glycolysis and gluconeogenesis occurred at the same time; you get hydrolysis of ATP w/no useful metabolic reaction
• wasteful if PFK1 and fructosebisphosphatase1 (FBPase1) operate at high rates at the same time

Question 5

cori cycle

Answer 5

-example of metabolic cooperation between tissues; burden shifted from muscle to liver (same thing with red blood cells and liver)

• rapidly contracting muscle does anaerobic glycolysis; pyruvate is reduced to lactate; produces 2 ATP
• lactate then diffuses out into blood and taken up by liver
• oxidized back to pyruvate and synthesize glucose in gluconeogenesis using 6ATP

Question 6

regulation of PFK2 and FBPase2

Answer 6

• both controlled in response to hormones insulin and glucagon
• fructose-2,6-bis P is synthesized from fru-6-P specifically as a regulator of PFK1 and FBPase1
• requires ATP and enzymes PFK2 (phosphorylation) and FBPase 2(deP); activity of these controlled in response to hormones
• PFK2 and FBPase2 activities are in one bifucntional enzyme
• in phosphorylated form, PFK2 is inactive and FBPase2 is active
• when [FBPase] is low, gluconeogenesis is stimulated and glycolysis inhibited
• glucagon activates PKA leading to phosphorylation thus stimulates gluconeogenesis
• insulin activates phosphatase so gluconeogenesis is low
• PFK and FBPase are in one bifunctional enzyme and can be controlled by phosphorylation
• in phosphorylated form