2012-12-03 7&8: CAC; ATP Synth -> Cell Resp Flashcards
Draw the TCA with just products (no enzymes)
acetyl-CoA—>citrate—>isocitrate—>α-KG—>succinyl-CoA—>succinate—>fumarate—>malate—>oxaloacetate—>back to Acetyl-CoA
What’s the mnemonic to remember substrates of the TCA?
A Citrate Is Kreb's Starting Substrate For Making Oxaloactetate
What’s the mnemonic to remember where reducing equivalents are generated?
N-O KS (NADH at O, K, and S1)
For (FADH2 at F)
GayS (GTP at S2)
Which steps are reversible?
FMO
What steps generate CO2?
isocitrate—>α-KG
α-KG—>succinyl-CoA
Which is the key regulatory enzyme in TCA?
isocitrate DH
—inhibited by: ATP
—activated by: ADP
Can you make acetyl-CoA back into glucose?
No
How does heart make acetyl-CoA
1) lactatepyruvate
2) pyruvate—PDH—>acetyl-CoA
When isocitrate DH is inhibited, where do the substrates go?
citrate builds up and heads to fatty-acid synthesis
What catalyzes malate—>oxaloacetate?
malate DH (mitochondrial isoform) —recall there's also a cytosolic malate DH used in the malate shuttle for gluconeogenesis
Draw the whole citric acid cycle with enzymes, reducing equivalents, and CO2 production.
oxaloacetate + acetyl-CoA—CITRATE SYNTHASE—>citrate—ACONITASE—>isocitrate—IDH—>α-KG—>α-KGDH—>succinyl-CoA—SUCCINATE THIOKINASE—>succinate—SDH—>fumarate—FUMARASE—>malate—MDH—>oxaloacetate
What is the mast mnemonic for TCA?
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)
Which of the following enzymes of the citric acid cycle is reversible?
a. Citrate Synthase
b. Ketoglutarate Dehydrogenase
c. Isocitrate Dehydrogenase
d. SuccinylCoA Synthase
D
succiny-CoA synthase is part of α-KGDH complex
What steps are irreversible?
The first step:
1. oxaloacetate + acetyl-CoA—CITRATE SYNTHASE—>citrate
And the steps that make CO2:
- isocitrate—IDH—>α-KG
- α-KG—α-KGDH—>succinyl-CoA
What happens to acetyl-CoA bound for FA synthesis?
HMG-CoA synthase—>HMG-CoA—HMG-CoA lyase—>acetoacetate
What is acetoacetate? Where is it metabolized?
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
How is EtOH metab’d?
- ethanol—ADH—>acetaldehyde (makes NADH)
- acetaldehyde—ALDH—>acetate (makes NADH)
- acetate—thiokinase—>acetyl-CoA
How does antibuse work?
inhibits ALDH, causes acetaldehyde to accumulate—>makes you feel really sick
Why is ethanol especially fattening?
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.
What effect does EtOH metab have on lactate metabolism?
Increase NADH/NAD+ ratio which inhibits lactate oxidation
—causes severe hypoglycemia and lactic acidosis
—”Don’t drink after exercising,” says Trumpower.
How is energy extracted from Methionine and the branched a.a.’s (isoleucine and valine)
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
How is TCA regulated?
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+
What TCA substrate is a porphyrin precursor?
succinyl-CoA
Which TCA substrate is a precursor for amino acids, purines and pyrimidines?
oxaloacetate
