rate-limiting unreviewed

HMG-CoA reductase (HMGCR)

1 reactions · 1 pathways

Cofactors used

CoA-SH · B5 (Pantothenic acid) NADP+ · B3 (Niacin) NADPH · B3 (Niacin)

Clinical / pharmacological. Target of statins; SREBP-2 regulated

What it does, reaction by reaction

1 reactions

Cholesterol Biosynthesis (Mevalonate Pathway) Lipid Metabolism · Cytosol + ER

step 3 Irreversible rate-limiting

HMG-CoA + 2 NADPH + 2 H+ → mevalonate + 2 NADP+ + CoA-SH

Converts HMG-CoA NADPH H+ into Mevalonate NADP+ CoA-SH

› Notes

ER-associated HMG-CoA reductase (HMGCR) performs a two-stage reduction via mevaldehyde. This is the rate-limiting, committed, and essentially irreversible step of cholesterol biosynthesis and the target of statins.

Showing all 1 reactions.

What accelerates and inhibits it

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

2 entries

Cholesterol Biosynthesis (Mevalonate Pathway)

Listed there as: HMG-CoA reductase

Accelerated by

Low intracellular sterol via SREBP-2; dephosphorylation; insulin

Inhibited by

Cholesterol/sterols (feedback, accelerated degradation); phosphorylation by AMPK; statins

Hormonal control

Insulin activates and induces expression; glucagon and energy stress inhibit through phosphorylation; thyroid hormone can increase expression

Lipoprotein Metabolism (Exogenous and Endogenous Pathways: chylomicrons, VLDL, LDL, HDL)

Listed there as: HMG-CoA reductase

Accelerated by

Low intracellular cholesterol; SREBP-2; insulin

Inhibited by

Sterols, AMPK phosphorylation, statins

Hormonal control

Insulin activates; glucagon/energy stress inhibit

Recent literature

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