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dolichol

Monday 25 May 2009

Dolichol refers to any of a group of long-chain mostly unsaturated organic compounds which are made up of varying numbers of isoprene units terminating in an α-saturated isoprenoid group, containing an alcohol functional group.

Biosynthesis

It is a product of the HMG-CoA reductase pathway, as characteristic for all terpenes produced via the mevalonate pathway.

First, a cis(or Z)-prenyltransferase catalyzes condensation of Farnesyl diphosphate (FPP) with a varying number (dependent on the particular cis-prenyltransferase) of isopentenyl diphoshate (IPP) molecules, resulting in polyprenyl diphosphate (also known as dehydrodolichyl diphosphate).

This subsequently undergoes loss of both phosphate groups resulting in a polyprenol (dehydrodolichol).

Last, the α isoprenoid unit is saturated by α-saturase (still a hypothetical enzyme), and this α-saturated polyprenyl alcohol is Dolichol.

Functions

Dolichols are adducted to proteins during post-translational modification. They activate and anchor sugar molecules on cellular membranes.

In addition, they play a role in protein N-glycosylation in the form of dolichol pyrophosphate by carrying the preassembled oligosaccharide Glc3-Man9-GlcNAc2 (where Glc is glucose, Man is mannose, and GlcNAc is N-acetylglucosamine) which is transferred to certain asparagine residues of nascent polypeptide chains.

Dolichol is also involved in transfer of the monosaccharides to the forming Glc3-Man9-GlcNAc2-Dolichol carrier.

Pathology

- Dolichol accumulates in tissues over time and has been suggested to be used as a biomarker for aging.

See also

- dolichol kinase