Mevalonate pathway



  The mevalonate pathway or HMG-CoA reductase pathway or mevalonate-dependent (MAD) route, is an important cellular N-glycosylation. It is also a part of steroid biosynthesis.

Regulation and feedback

Several key enzymes can be activated through receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation.

For more information on regulation, see HMG-CoA reductase

Pharmacology

A number of drugs target the mevalonate pathway:

Alternative

Plants and apicomplexan protozoa such as malaria parasites have the ability to produce their non-mevalonate pathway instead.

Reactions

Reaction Diagram Enzyme
citric acid cycle) is converted to acetoacetyl-CoA thiolase
Acetyl-CoA condenses with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA).
HMG-CoA synthase
HMG-CoA is reduced to mevalonate by statins.
HMG-CoA reductase
Mevalonate to 5-phosphomevalonate.
mevalonate kinase
5-phosphomevalonate to 5-pyrophosphomevalonate.
phosphomevalonate kinase
Mevalonate-5-pyrophosphate to 3-isopentenyl pyrophosphate (IPP) (see also HIDS).

mevalonate-5-pyrophosphate decarboxylase
3-isopentenyl pyrophosphate is isomerized to dimethylallyl pyrophosphate.
isopentenyl pyrophosphate isomerase

References

  1. Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th ed. New York: W.H. Freeman. xxxviii, 974, [976] (various pagings). ISBN 0-7167-4684-0.
  2. Swanson KM, Hohl RJ. Anti-cancer therapy: targeting the mevalonate pathway. Curr Cancer Drug Targets 2006;6:15-37. PMID 16475974.
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Metabolism: Mevalonate pathway
Acetyl-Coenzyme A acetyltransferase - HMG-CoA synthase - HMG-CoA reductase - Mevalonate kinase - Phosphomevalonate kinase - Pyrophosphomevalonate decarboxylase - Isopentenyl-diphosphate delta isomerase
 
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