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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 · from cache · sorted by publication date

  1. 1
    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
  2. 2
    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
  3. 3
    Beyond proteostasis: LONP1 as an immunometabolic checkpoint in health and disease.

    Xie L, Wu LH, Ni XC, Zhang JN. · 2026-06-16

    unreviewed
  4. 4
    Acetoacetyl-CoA synthetase modulates lipid partitioning and cholesterol-related gene expression in NEFA-challenged neonatal bovine hepatocytes.

    Tian Y, Wang S, Loor JJ, Fan W, Chang Y, Yang T, Zhang B, Xia C, Xu C, Li X, Yang W. · 2026-05-11

    unreviewed
  5. 5
    Perilipin 2 drives cisplatin-induced acute kidney injury in young but not aged kidneys.

    Zhu S, Dai C, Zheng K, Gui Y, Liu JJ, Li J, Yu Y, Liu S, Zhou D. · 2026-08-11

    unreviewed
  6. 6
    Network Pharmacology Combined With Metabonomics and Transcriptomics Reveals the Mechanism of <i>Rubus</i> Chingii Hu in Alleviating Nephrotoxicity Caused by Tripterygium Glycosides Tablet.

    Zhang C, Zhang Z, Zhou T, Zhang L. · 2026-08-04

    unreviewed
  7. 7
    Highly expressed ACSF2 contributes to butyrate utilization in the rumen epithelium.

    Song M, Qin J, Tian J, Zhang K, Zhang Y, Xiang X, Zhu W, Mao S, Liu J, Huang Z. · 2026-08-02

    unreviewed
  8. 8
    Yin Yang 1 Specifically Supports the Development of Olig2 Positive Cerebellar Astrocytes.

    Zarei-Kheirabadi M, Tyc KM, Dain L, Kheirabadi MA, Hanco J, Mockenhaupt K, Munir S, McQuiston A, Singh SK, Ko… · 2026-08-01

    open access unreviewed
  9. 9
    Clinical and neurodevelopmental features of chromosome 1 copy number variations in children.

    Yüksel Ülker A, Usluer E, Kaplan İ. · 2026-05-30

    unreviewed
  10. 10
    Renal Ketogenesis Protects Against Ischemic Kidney Injury.

    Feola K, Venable AH, Rasouli M, Haley EG, Jadhav C, Monroy R, McCoy T, Huen SC. · 2026-01-21

    cited 1× unreviewed

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