2012-12-03 7&8: CAC; ATP Synth -> Cell Resp

Question 1

Draw the TCA with just products (no enzymes)

Answer 1

acetyl-CoA—>citrate—>isocitrate—>α-KG—>succinyl-CoA—>succinate—>fumarate—>malate—>oxaloacetate—>back to Acetyl-CoA

Question 2

What’s the mnemonic to remember substrates of the TCA?

Answer 2

A
Citrate
Is
Kreb's
Starting
Substrate
For
Making
Oxaloactetate

Question 3

What’s the mnemonic to remember where reducing equivalents are generated?

Answer 3

N-O KS (NADH at O, K, and S1)
For (FADH2 at F)
GayS (GTP at S2)

Question 4

Which steps are reversible?

Answer 4

FMO

Question 5

What steps generate CO2?

Answer 5

isocitrate—>α-KG

α-KG—>succinyl-CoA

Question 6

Which is the key regulatory enzyme in TCA?

Answer 6

isocitrate DH
—inhibited by: ATP
—activated by: ADP

Question 7

Can you make acetyl-CoA back into glucose?

Answer 7

No

Question 8

How does heart make acetyl-CoA

Answer 8

1) lactatepyruvate

2) pyruvate—PDH—>acetyl-CoA

Question 9

When isocitrate DH is inhibited, where do the substrates go?

Answer 9

citrate builds up and heads to fatty-acid synthesis

Question 10

What catalyzes malate—>oxaloacetate?

Answer 10

malate DH (mitochondrial isoform)
—recall there's also a cytosolic malate DH used in the malate shuttle for gluconeogenesis

Question 11

Draw the whole citric acid cycle with enzymes, reducing equivalents, and CO2 production.

Answer 11

oxaloacetate + acetyl-CoA—CITRATE SYNTHASE—>citrate—ACONITASE—>isocitrate—IDH—>α-KG—>α-KGDH—>succinyl-CoA—SUCCINATE THIOKINASE—>succinate—SDH—>fumarate—FUMARASE—>malate—MDH—>oxaloacetate

Question 12

What is the mast mnemonic for TCA?

Answer 12

SUBSTRATES
A
Citrate
Is
Kreb's
Starting
Substrate
For
Making
Oxaloactetate

REDUCING EQUIVALENTS
NO KS
For
GayS

ENZYMES (Cont’d from above)
CA(lifornia) [citrate synthase, aconitase]
Sounds [succinate thiokinase]
Fabulous [fumarase]
(all the rest are just _____ dehydrogenases)

CO2 PRODUCTION
Gassy Greeks (either side of α-KG)

Question 13

Which of the following enzymes of the citric acid cycle is reversible?

a. Citrate Synthase
b. Ketoglutarate Dehydrogenase
c. Isocitrate Dehydrogenase
d. SuccinylCoA Synthase

Answer 13

D

succiny-CoA synthase is part of α-KGDH complex

Question 14

What steps are irreversible?

Answer 14

The first step:
1. oxaloacetate + acetyl-CoA—CITRATE SYNTHASE—>citrate

And the steps that make CO2:

2. isocitrate—IDH—>α-KG
3. α-KG—α-KGDH—>succinyl-CoA

Question 15

What happens to acetyl-CoA bound for FA synthesis?

Answer 15

HMG-CoA synthase—>HMG-CoA—HMG-CoA lyase—>acetoacetate

Question 16

What is acetoacetate? Where is it metabolized?

Answer 16

It is a ketone body (elevated in DM where there is higher reliance on FA metab).

I cannot be metab’d in liver, only heart, muscle and renal cortex

Question 17

How is EtOH metab’d?

Answer 17

1. ethanol—ADH—>acetaldehyde (makes NADH)
2. acetaldehyde—ALDH—>acetate (makes NADH)
3. acetate—thiokinase—>acetyl-CoA

Question 18

How does antibuse work?

Answer 18

inhibits ALDH, causes acetaldehyde to accumulate—>makes you feel really sick

Question 19

Why is ethanol especially fattening?

Answer 19

Ethanol makes 2 NADH as it is converted to acetyl CoA:
—diminishes the need to oxidize fat
—puts C into TCA while bypassing the PDH rxn, that controls the entry of carbon into the citric acid cycle.

Question 20

What effect does EtOH metab have on lactate metabolism?

Answer 20

Increase NADH/NAD+ ratio which inhibits lactate oxidation
—causes severe hypoglycemia and lactic acidosis
—”Don’t drink after exercising,” says Trumpower.

Question 21

How is energy extracted from Methionine and the branched a.a.’s (isoleucine and valine)

Answer 21

methionine and the branched chain! amino acids enter the citric acid cycle via propionyl CoA—>Methylmalonyl CoA—Methylmalonyl CoA mutase—>succinyl-CoA
**Methylmalonyl CoA mutase is one of only two enzymes in body that needs B12

Question 22

How is TCA regulated?

Answer 22

Three points of reg:
1. MAIN POINT: Isocitrate DH
—inhibited by: ATP, NADH
2. citrate synthase
—inhibited by: ATP, succinyl-CoA
3. also Pyrvuate DH—>acetyl-CoA
—inhibited by: ATP, acetyl-CoA and NADH
—stimulated by: Ca2+

Question 23

What TCA substrate is a porphyrin precursor?

Answer 23

succinyl-CoA

Question 24

Which TCA substrate is a precursor for amino acids, purines and pyrimidines?

Answer 24

oxaloacetate