gluconeogenesis

Question 1

function of gluconeogensis?

Answer 1

to synthesize glucose during PROLONGED fast

Question 2

overall equation of gluconeogenesis?

Answer 2

2 pyruvate + 4ATP + 2GTP + 2NADH + 6H2O→ glucose + 4ADP +2GDP + 6Pi + 2NAD+ + 2H+

vs glycolysis: glucose + 2ADP + 2Pi + 2NAD+→ 2 pyruvate + 2ATP + 2NADH + H2O + 2H+

Question 3

how is glucose obtained by our liver during different fasting lengths?

Answer 3

short fast: glycogen stores
long fast: gluconeogenesis

Question 4

where is gluconeogenesis carried out? (tissue & organelles)

Answer 4

• most enzymes are cytosolic except:
  1. pyruvate carboxylase (mitochondria)
  2. glucose-6-phosphatase (ER)

mainly in liver & kidneys (gluconeogenic tissues→ only they can export glucose)

Question 5

why can’t skeletal muscles undergo gluconeogenesis?

Answer 5

they lack glucose-6-phosphatase

Question 6

what are the 3 irreversible steps of glycolysis?

Answer 6

1. glucose→ G6P
2. F6P→ F16B
3. phosphoenolpyruvate→ pyruvate

Question 7

what are the precursors for gluconeogenesis? (4)

Answer 7

entry via pyruvate: (reversible reactions)
1. lactate (fr anaerobic glycolysis)
2. alanine (fr muscle breakdown)

entry via oxaloacetate:
3. glutamine

entry via glycerol-3-P:
4. glycerol (lipolysis)→ glucerol3p→ dihydroxyacetone P

Question 8

what is the cori cycle?

Answer 8

liver: lactate→ pyruvate→ glucose
muscle: lactate← pyruvate← glucose (anaerobic glycolysis)

Question 9

what is the alanine/cahill cycle?

Answer 9

liver: alanine→ pyruvate→ glucose
muscle: alanine← pyruvate← glucose

• to shuttle pyruvate fr muscles to liver (only alanine can be transported into liver) then convert to glucose in the liver

Question 10

how does glucose get generated form lipolysis?

Answer 10

triglycerol→ (lipase)→ glycerol→ glycerol-3-P→ DHAP→ enters gluconeogenic pathway

Question 11

what are the steps involved in pyruvate→ phosphoenolpyruvate? (3)

Answer 11

1. (mitochondria) pyruvate→[PC + biotin]→ oxaloacetate
2. shuttling of oxaloacetate to cytosol via (matrix) oxaloacetate→ malate→ (cytosol)→ oxaloacetate
3. (cytosol) oxaloacetate→ phosphoenolpyruvate

Question 12

what is the pathophysiology/effects of pyruvate carboxylase deficiency? (4)

Answer 12

pyruvate accumulates→
1. increased lactate
2. increased acetyl CoA

fall in oxaloacetate→
3. fall in TCA intermediates
4. fall in ATP production

Question 13

what is the pathophysiology of glucose-6-phosphatase deficiency?

Answer 13

• fall in glucose→ fasting hypoglycemia
• G6P accumulates→ increased glycogen→ organomegaly
• G6P accumulates→ HMP shunt→ increased nucleotide metabolism→ increased uric acid

Question 14

what is the link between DM and gluconeogenesis?

Answer 14

DM is due to insulin deficiency→ unopposed glucagon action→ stimulates gluconeogenesis→ increase glucose

Question 15

how is gluconeogenesis regulated in high energy state e.g. resting?

Answer 15

high energy state→ increase gluconeogenesis as don’t need to produce ATP anymore

1. high ATP, high citrate→ upregulate F16BP→ upregulate gluconeogenesis
2. high acetyl CoA→ upregulate PC→ upregulate gluconeogenesis

Question 16

how is gluconeogenesis regulated in low energy state e.g. exercising?

Answer 16

low energy state→ decrease gluconeogenesis to increase pyruvate/ATP levels

1. ADP→ inhibits PC and PEPCK→ inhibit gluconeogenesis
2. AMP→ inhibit F16BP→ inhibit gluconeogenesis

Question 17

how is gluconeogenesis regulated after meals?

Answer 17

high glucose→ high insulin→ upregulate F26P2→ inhibits F16P2→ inhibits gluconeogenesis

Question 18

how is gluconeogenesis regulated in fasting state? (2)

Answer 18

• low glucose→ high glucagon→ downregulate F26P2→ decrease F16P2 inhibition→ increase gluconeogenesis
• high glucagon→ increase transcription of gluconeogenesis enzymes→ increase gluconeogenesis