rate-limiting unreviewed

Mitochondrial HMG-CoA synthase (HMGCS2)

1 reactions · 1 pathways

Cofactors used

CoA-SH · B5 (Pantothenic acid) H2O

Clinical / pharmacological. Rate-limiting for ketogenesis; induced by fasting/PPAR-alpha

What it does, reaction by reaction

1 reactions

Ketogenesis Lipid Metabolism · Liver mitochondrial matrix

step 2 Irreversible/directional rate-limiting

Acetoacetyl-CoA + acetyl-CoA + H2O → 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) + CoA-SH

Converts Acetoacetyl-CoA Acetyl-CoA H2O into 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) CoA-SH

› Notes

Mitochondrial HMG-CoA synthase (HMGCS2) catalyzes this condensation. It is the rate-limiting and committed step of ketogenesis; it is distinct from cytosolic HMG-CoA synthase used in cholesterol synthesis.

Showing all 1 reactions.

What accelerates and inhibits it

Regulation is pathway-specific, so each context is listed separately

1 entries

Ketogenesis

Accelerated by

High acetyl-CoA from β-oxidation; PPARα-mediated expression; fasting

Inhibited by

High insulin/carbohydrate availability; low fatty-acid delivery

Hormonal control

Glucagon and low insulin induce expression indirectly through fasting transcriptional programs; insulin suppresses ketogenesis

Recent literature

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