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Which can inhibit HMG COA into mevalonate

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HMG-CoA reductase inhibitors statins mevalonate pathway pharmacology

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Statins — Inhibitors of HMG-CoA Reductase

The enzyme HMG-CoA reductase catalyzes the NADPH-dependent reduction of HMG-CoA → mevalonate, which is the rate-limiting step in cholesterol biosynthesis. The drug class that inhibits this step is the statins (HMG-CoA reductase inhibitors).
Cholesterol biosynthesis pathway showing statins blocking HMG-CoA reductase

Mechanism

Statins contain a mevalonic acid-like moiety that competitively inhibits the active site of HMG-CoA reductase, preventing the conversion of HMG-CoA to mevalonate. This:
  1. Reduces hepatic cholesterol synthesis
  2. Upregulates LDL receptor expression (via SREBP-2 activation) → increased LDL clearance from blood
  3. Decreases VLDL production (at higher doses)

Statin Drugs (by potency)

DrugRelative Potency
RosuvastatinHighest
AtorvastatinHigh
SimvastatinModerate–High
LovastatinModerate
PravastatinModerate
FluvastatinLower
PitavastatinModerate

Key Points

  • The reaction requires 2 NADPH as a cofactor (oxidized to NADP⁺)
  • Inhibiting HMG-CoA reductase also reduces downstream isoprenoid products (ubiquinone, dolichol, prenylated proteins) — relevant to statin side effects (e.g., myopathy)
  • Statins are competitive inhibitors — they increase apparent Km without changing Vmax
Source: Goodman & Gilman's Pharmacological Basis of Therapeutics; Lippincott's Illustrated Reviews: Biochemistry, 8th ed.
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