Ketosis

Question 1

Front

Answer 1

Back

Question 2

What happens if oxaloacetate (OAA) is depleted?

Answer 2

• TCA cycle halts (no citrate formation).<br></br>- Acetyl-CoA diverts to ketogenesis → ketone bodies.<br></br>- Fatty acid synthesis stops (no cytosolic acetyl-CoA).

Question 3

Why can’t acetyl-CoA cross the mitochondrial membrane?

Answer 3

No transporter exists for acetyl-CoA. Citrate carries acetyl groups to cytosol instead.

Question 4

Role of the citrate shuttle in fatty acid synthesis

Answer 4

1. Mitochondrial acetyl-CoA + OAA → citrate.<br></br>2. Citrate exits to cytosol.<br></br>3. ATP citrate lyase (ACL) splits citrate → acetyl-CoA (for FAS) + OAA (returns to mitochondria).

Question 5

Clinical consequence of OAA depletion (e.g., diabetes)

Answer 5

• Ketogenesis ↑ (DKA).<br></br>- Fatty acid synthesis ↓.<br></br>- Gluconeogenesis consumes OAA.

Question 6

Enzyme that converts citrate back to acetyl-CoA in cytosol

Answer 6

ATP citrate lyase (ACL). Activated by insulin in fed state.

Question 7

Key difference: Fed vs. fasting state for citrate shuttle

Answer 7

Fed: Insulin ↑ → citrate shuttle active (FAS).<br></br>Fasting: Shuttle off → acetyl-CoA → ketones.

Question 8

Diabetic ketoacidosis (DKA) and OAA

Answer 8

• OAA depleted for gluconeogenesis.<br></br>- Acetyl-CoA → ketones (via HMG-CoA synthase).<br></br>- Results in metabolic acidosis.

Question 9

Mnemonic for citrate shuttle

Answer 9

‘Citrate = Acetyl-CoA’s Lyft to the cytosol!’

Question 10

Drug target in ketogenesis

Answer 10

HMG-CoA synthase (inhibited by hydroxybutyrate in feedback loop).

Question 11

USMLE/PLAB Q: Why does fatty acid synthesis stop in starvation?

Answer 11

No citrate shuttle (OAA depleted for gluconeogenesis → no cytosolic acetyl-CoA).