Mevalonate pathway

Jump to navigation Jump to search
Mevalonate pathway

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

WikiDoc Resources for Mevalonate pathway

Articles

Most recent articles on Mevalonate pathway

Most cited articles on Mevalonate pathway

Review articles on Mevalonate pathway

Articles on Mevalonate pathway in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Mevalonate pathway

Images of Mevalonate pathway

Photos of Mevalonate pathway

Podcasts & MP3s on Mevalonate pathway

Videos on Mevalonate pathway

Evidence Based Medicine

Cochrane Collaboration on Mevalonate pathway

Bandolier on Mevalonate pathway

TRIP on Mevalonate pathway

Clinical Trials

Ongoing Trials on Mevalonate pathway at Clinical Trials.gov

Trial results on Mevalonate pathway

Clinical Trials on Mevalonate pathway at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Mevalonate pathway

NICE Guidance on Mevalonate pathway

NHS PRODIGY Guidance

FDA on Mevalonate pathway

CDC on Mevalonate pathway

Books

Books on Mevalonate pathway

News

Mevalonate pathway in the news

Be alerted to news on Mevalonate pathway

News trends on Mevalonate pathway

Commentary

Blogs on Mevalonate pathway

Definitions

Definitions of Mevalonate pathway

Patient Resources / Community

Patient resources on Mevalonate pathway

Discussion groups on Mevalonate pathway

Patient Handouts on Mevalonate pathway

Directions to Hospitals Treating Mevalonate pathway

Risk calculators and risk factors for Mevalonate pathway

Healthcare Provider Resources

Symptoms of Mevalonate pathway

Causes & Risk Factors for Mevalonate pathway

Diagnostic studies for Mevalonate pathway

Treatment of Mevalonate pathway

Continuing Medical Education (CME)

CME Programs on Mevalonate pathway

International

Mevalonate pathway en Espanol

Mevalonate pathway en Francais

Business

Mevalonate pathway in the Marketplace

Patents on Mevalonate pathway

Experimental / Informatics

List of terms related to Mevalonate pathway

Overview

The mevalonate pathway or HMG-CoA reductase pathway or mevalonate-dependent (MAD) route, is an important cellular metabolic pathway present in all higher eukaryotes and many bacteria. It is important for the production of dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP), which serve as the basis for the biosynthesis of molecules used in processes as diverse as protein prenylation, cell membrane maintenance, hormones, protein anchoring, and N-glycosylation. It is also a part of steroid biosynthesis.

Regulation and feedback

Several key enzymes can be activated through DNA transcriptional regulation on activation of SREBP (Sterol Regulatory Element-Binding Protein-1 and -2). This intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein uptake by up-regulating the LDL 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 isoprenoids (terpenoids) using an additional alternative pathway called the methylerythritol phosphate (MEP) or non-mevalonate pathway, which takes place in their plastids. In addition, most eubacteria including important pathogens, such as Mycobacterium tuberculosis, synthesize IPP and DMAPP via the non-mevalonate pathway instead.

Reactions

Reaction Diagram Enzyme
Acetyl-CoA (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 NADPH. This reaction occurs in the cytosol. It is the committed step in cholesterol synthesis, which is why the enzyme catalyzing the reaction is a target of 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.

External Links

Template:WikiDoc Sources Template:WH