Skip to content
MS
Sign in
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

Refresh

Europe PMC · fetched just now · sorted by publication date

  1. 1
    Statement of Retraction: HMGCS2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress.

    · 2026-10-01

    open access unreviewed
  2. 2
    Hepatocyte SLC31A1-dependent copper accumulation contributes to hepatic glucose and lipid metabolic disturbances through AMPKα1 inactivation.

    Cheng YQ, Wei M, Yang L, Zhuang YY, Lu QB. · 2026-09-11

    open access unreviewed
  3. 3
    Lactate induces renal lipid accumulation and aggravates renal fibrosis by inhibiting the PPARα signaling pathway and fatty acid oxidation.

    Wang W, Gao Y, Chen Y, Cheng M, Wei L, Sang Y, Zhang L, Dai R, Wang Y. · 2026-03-10

    open access unreviewed
  4. 4
    Targeting mitochondrial quality control in diabetic kidney disease: emerging therapeutic opportunities.

    Luo J, Lu F, Cuciureanu M, Xu X, Dong H, Gong M. · 2026-02-03

    cited 2× open access unreviewed
  5. 5
    Research progress in metabolic reprogramming and targeting metabolic pathways for clear cell renal cell carcinoma.

    Yao JT, Hu PC, Li XW, Xu JC, Wang KJ, Ye SZ, Meng XY, Chen HC, Liang Y, Ma Q. · 2025-12-19

    open access unreviewed
  6. 6
    Sotagliflozin Reprograms Hepatic Lipid Metabolism and Attenuates Atherosclerosis Beyond Empagliflozin in CKM Mice

    · 2026-10-01

    open access unreviewed
  7. 7
    Extracts of okra mucilage protect intestinal homeostasis through gut microbiota and immune responses.

    Qing M, Sun B, Li Y, Meng Z, Lu Q, Li K, Chen G. · 2026-10-05

    unreviewed
  8. 8
    Kidney Epithelial AKT Controls Potassium Homeostasis and Metabolic Adaptation.

    Inoue MK, Zhang Y, Rivera AV, Hasenour CM, Arroyo JP, Bock F, Yu A, Kaji I, Ferdaus MZ, Delpire E, Young JD, … · 2026-10-01

    unreviewed
  9. 9
    Proteomic Signatures of Noise-Induced Hearing Loss in the Mouse Cochlea.

    Batissoco AC, Alencar-Coutinho D, Ferreira-Scatone AC, Diogo-Cavassana S, Oiticica J, Lezirovitz K, Bento RF. · 2026-10-01

    open access unreviewed
  10. 10
    Assessing clinical relevance of off-target effects observed at suprapharmacological concentrations of SGLT2 inhibitors. Reply.

    Abdualkader AM, Al Batran R. · 2026-10-01

    cited 1× open access unreviewed

External claims. These come from an index outside this database and are not checked against it. Treat them as leads.