Showing metabocard for Dolichol phosphate (MMDBc0033164)
Record Information
Version
1.0
Status
Detected and Quantified
Creation Date
2021-11-19 04:37:18 UTC
Update Date
2022-12-15 22:51:54 UTC
MiMeDB ID
MMDBc0033164
Metabolite Identification
Common Name
Dolichol phosphate
Description
Dolichol phosphate is the most prevalent polyisoprenyl-glycosyl carrier found in mammals. It is involved in reactions such as the C-4 and O-mannosylation of proteins, the formation of glycosylphosphatidylinositol (GPI) anchors and the N-glycosylation of proteins. The chain length of eukaryotic dolichol molecules differs from 14 to 17 isoprene units in unicellular organisms like yeast whereas mammalian cells produce dolichol with 18-21 isoprene units. During the de novo synthesis of dolichol in eukaryotes, farnesyl pyrophosphate, a metabolite of cholesterol biosynthesis, is elongated by successive condensations to isopentenyl pyrophosphate molecules. These reactions are catalyzed by cis-isopentenyltransferases. After the polyisoprene pyrophosphate chain has reached its final length, both phosphate residues are released by mono- or pyrophosphatases. The isoprene unit of the polyprenol is then reduced by a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent microsomal reductase. The final step in dolichol phosphate synthesis is catalyzed by dolichol kinase (DK1), an enzyme that transfers a phosphate from choline-phosphate cytidine triphosphate (CTP) to dolichol. Once synthesized, dolichol phosphate can react with cytosolic GDP-mannose in the endoplasmic reticulum membrane to form dolichyl phosphate D-mannose. A new inherited metabolic disorder, Dolichol kinase (DK1) deficiency has recently been discovered. Affected patients present with a very severe clinical phenotype, with death in early infancy. Symptoms include secondary microencephaly, dry, thin, parchmentlike skin, hyperkeratosis, minimal hair growth and muscular hypotonia. (PMID: 17273964 ).
Kranz C, Jungeblut C, Denecke J, Erlekotte A, Sohlbach C, Debus V, Kehl HG, Harms E, Reith A, Reichel S, Grobe H, Hammersen G, Schwarzer U, Marquardt T: A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy. Am J Hum Genet. 2007 Mar;80(3):433-40. doi: 10.1086/512130. Epub 2007 Jan 31. [PubMed:17273964 ]
