Mevalonate pathway

The HMG-CoA reductase pathway is an important cellular metabolic pathway present in virtually all organisms. It forms hydrophobic molecules for tasks as diverse as cell membrane maintenance, hormones, protein anchoring and N-glycosylation.

Reactions

The HMG-CoA reductase pathway

• Acetyl-CoA (citric acid cycle) and acetoacetyl-CoA to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA);
• HMG-CoA to mevalonate - by HMG-CoA reductase (target of statins);
• Mevalonate to Isopentenyl-pyrophosphate (IPP) - by mevalonate kinase (see also HIDS);
• IPP to geranyl-PP by farnesyl-PP synthetase
• Geranyl-PP to farnesyl-PP by farnesyl-PP synthetase (target of the bisphosphonates)

Farnesyl-PP is perhaps the central product of the pathway. It is metabolised further by a number of steps into:

• Cholesterol
• Prenylation chains (see lipid anchored protein)
• Haem A
• Dolichol (plays a role in glycosylation of proteins)
• Ubiquinon (essenial in protein catabolism)

Pharmacology

A number of drugs targets the HMG-CoA reductase pathway:

• Statins (used for elevated cholesterol levels);
• Bisphosphonates (used for osteoporosis).