PPP, Gluconeogenesis and Cori Pathway

Question 1

How does the Pentose Phosphate pathway connect to glycolysis?

Answer 1

it branches off at G6P and branches back in at F6P and GAP

Question 2

What is the committing enzyme of the Pentose Phosphate pathway?

Answer 2

glucose-6-phosphate dehydrogenase

Question 3

what is the output of the PPP?

Answer 3

ribose-6-phosphate and NADPH

Question 4

where is the PPP mostly present?

Answer 4

liver, adipose tissue, RBCs

Question 5

what are the metabolic uses of NADPH?

Answer 5

Fatty acid synthesis, cholesterol synthesis and reduction reactions

Question 6

Compare the cytosolic concentrations of [NAD+]/[NADH] and [NADP+]/[NADPH].

Answer 6

• [NAD+]/[NADH] = 1000
• [NADP+]/[NADPH] = 0.01

Question 7

Why is NADPH so important in RBCs? What would happen if there wasn’t enough?

Answer 7

• it maintains the pool of GSH which prevents peroxide-mediated hemolysis of the red blood cell
• deficiency would mean that RBCs couldn’t handle the extra oxidants and they would damage the cell membranes and the cells would lyse

Question 8

what is ribose-5-phosphate needed for?

Answer 8

it is precursor for nucleotide synthesis

Question 9

what is the purpose of the oxidative reactions in the PPP and how are they regulated?

Answer 9

• to produce NADPH (2 NADPH produced per G6P) – irreversible steps
• by G6PDH, which is highly specific to NADP+ and strongly inhibited by NADPH

Question 10

what is isomerization and epimerization?

Answer 10

• iso: interchange of groups between carbons
• epi: interchange of groups on a single carbon

Question 11

what is the purpose of the isomerization and epimerization in the PPP?

Answer 11

to make ribose-5-phosphate

Question 12

how much Ru5P is needed to produce ribose-5-phosphate?

Answer 12

3

Question 13

what is the purpose of the C-C bond cleavage and formation reactions in PPP?

Answer 13

to recycle R5P and Xu5P

Question 14

What determines the fate of G6P?

Answer 14

the cellular needs of ATP, NADPH, and R5P

Question 15

What happens in the following situations:
1. Cell needs both NADPH and nucleotides.
2. Cell needs NADPH only
3. Cell needs nucleotides only

Answer 15

1. NADPH and R5P produces and excess R5P and Xu5P converted to F6P and GAP
2. NADPH and R5P produces and all R5P and Xu5P converted to F6P and GAP
3. F6P and GAP used to make R5P

Question 16

where does gluconeogenesis occur?

Answer 16

liver (major) and kidney (minor)

Question 17

When does gluconeogenesis occur?

Answer 17

• when fasting
• dietary glucose not available
• exhaustion of intracellular glucose
• glycogen pol in liver is depleted
• blood glucose are about to go below normal

Question 18

what are the substrates of gluconeogenesis?

Answer 18

• lactate
• pyruvate
• intermediates of the CAC
• amino acids (muscle)

Question 19

briefly explain gluconeogenesis.

Answer 19

• shares glycolysis reversible steps
• pyruvate becomes oxaloacetate by pyruvate carboxylase (ATP required)
• Oxaloacetate becomes phosphenolpyruvate (PEP) with PEPCK (GTP required)
• once at F1,6P, fructose bisphosphate transforms it back to F6P
• then, once G6P, becomes glucose with glucose-6-phosphatase

Question 20

what does gluconeogenesis require?

Answer 20

• pyruvate
• energy (from catabolism of fatty acids)
• acetyl-CoA pyruvate carboxylase activator)

Question 21

Explain the Cori Cycle.

Answer 21

• in muscle, lactate is produced to regenerate NAD+ under anaerobic condition
• this lactate can then be transported into the liver, where it can be converted to glucose by gluconeogenesis
• that glucose can then be transported back to the muscle where it can be used as energy