Lecture 18: Oxidative Phosphorylation, Gluconeogenesis

Question 1

How does aKG compare to PDH?

Answer 1

aKG and PDH are similar in structure and cofactors (TPP, FAD, lipoic acid) but aKG isn’t regulated by phosphorylation.

Question 2

Respiratory control ratio

Answer 2

O2 consumption rate with ADP / without ADP in mitochondrion

Question 3

P/O ratio

Answer 3

ADP / change in O2

Question 4

What does DNP (2,4-dinitrophenol) do?

Answer 4

DNP is a classic uncoupler of oxidative phosphorylation

Question 5

ETC carriers

Answer 5

1. Flavins (e.g. FMN)
2. Non-heme Fe proteins (e.g. FeS)
3. Heme iron proteins (e.g. cytochromes)
4. Ubiquinone (CoQ)

Question 6

ETC inhibitors

Answer 6

Rotenone, amytal –| complex 1
Antimycin A –| complex 3
CO, N3-, HCN, H2S –| complex 4
Oligomycin –| complex 5

Question 7

Which reducing equivalent shuttle is used in which tissues?

Answer 7

Liver uses more malate-aspartate, muscle uses more glycerol-P (more efficient, less NADH buildup)

Question 8

How much ATP is generated by full oxidation of 1 molecule of glucose?

Answer 8

30 to 38 ATP, depending on whether you use classical or old numbers (36/30) and whether you use glycerol-P or malate-aspartate shuttle (36/38 or 30/32)

Question 9

Chemiosmotic theory

Answer 9

ETC creates a proton gradient that ATP synthase uses, both in concentration and in charge

Question 10

Leber hereditary optic neuropathy

Answer 10

Mitochondrial gene mutation for ETC complexes; maternally inherited

Question 11

How is pyruvate carboxylase regulated?

Answer 11

Pyruvate carboxylase requires acetyl-CoA to be activated. Thus insulin, inhibiting lipolysis for FA oxidation, indirectly inhibits gluconeogen.

Question 12

How does fatty liver contribute to glucose dysregulation in obesity?

Answer 12

Fat in the liver can be an alternate supply of acetyl-CoA, resulting in less inhibition of gluconeogenesis by insulin at the liver

Question 13

How is F16bPase regulated?

Answer 13

AMP and F26bP inhibit F16bPase

Question 14

What is an important cofactor for PEP carboxykinase in gluconeogenesis?

Answer 14

GTP, which comes from the TCA cycle. Thus gluconeogen. can only occur with TCA activity, indicating glucose consumption.

Question 15

Adaptive gluconeogenesis behavior in the liver

Answer 15

Gluconeogenesis-specific enzymes are upregulated with starvation/low-carb diets in the liver

Question 16

What is the purpose of the Cori/Ala cycles?

Answer 16

Both bring carbon fuel to skeletal muscle from the liver (glucose) enabling continued glycolysis.

Question 17

When is the Cori cycle used over the Ala cycle?

Answer 17

The Cori cycle (lactate) is more likely in intense exercise, while Ala is more in low-intensity exercise (significant contribution for muscle energy)