dolicholfosfat

Dolichol phosphate, also known as dolichyl phosphate, is a long-chain polyisoprenoid lipid anchored in the membranes of the endoplasmic reticulum. It acts as a lipid carrier that supports the assembly and transfer of oligosaccharide chains in eukaryotic N-linked glycosylation and participates in related glycan assembly processes such as GPI-anchor biosynthesis.

Structure and occurrence: Dolichol consists of a hydrophobic polyisoprenoid chain of varying length (often around 19 isoprene units in humans) attached to a phosphate group at the terminal carbon. The molecule is embedded in the ER membrane, where it serves as a localized scaffold for glycan assembly.

Biosynthesis and function: Dolichol is produced via the mevalonate pathway, elongated to form dolichol, and phosphorylated by dolichol kinase to yield dolichol phosphate (Dol-P). Dol-P can be further converted to dolichyl pyrophosphate (Dol-PP), which acts as the carrier for the assembly of the universal N-linked glycan precursor. This precursor, typically Glc3Man9GlcNAc2 linked to Dol-PP, is transferred en bloc to nascent polypeptides by the oligosaccharyltransferase complex. Dolichol phosphate and its derivatives also participate in other glycosylation-related pathways, including the biosynthesis of GPI anchors, which attach certain proteins to the membrane.

Clinical significance: Impairments in dolichol phosphate metabolism or in the broader glycosylation pathway can cause congenital disorders of glycosylation (CDG). CDG manifest with multisystemic symptoms, reflecting the essential role of dolichol phosphate–dependent glycosylation in protein maturation and trafficking. Some diagnostic and research approaches assess dolichol/dolichyl phosphate levels as part of glycosylation disorders.

See also: N-linked glycosylation, oligosaccharyltransferase, dolichol, dolichyl phosphate kinase, congenital disorders of glycosylation.