Dolichol (Dol)

Dolichol refers to a class of long-chain isoprenoid alcohols, typically containing 17 to 21 isoprene units in humans, that serve as essential lipid carriers in the endoplasmic reticulum (PubChem CID 5460554). Its phosphorylated form, dolichol phosphate, acts as the obligate scaffold for the assembly of the 14-sugar oligosaccharide precursor required for N-linked protein glycosylation (Buczkowska et al., 2015, DOI: 10.1111/febs.13388). This glycosylation process is fundamental for the maturation, folding, and trafficking of a vast array of proteins, including cell-surface receptors and secreted antibodies. While dolichol is not a protein target itself, its biosynthesis is part of the mevalonate pathway, making it sensitive to HMG-CoA reductase inhibitors like statins, which can lead to reduced dolichol pools (Grünler et al., 1994, DOI: 10.1016/0005-2760(94)90045-0). Genetic defects in enzymes responsible for dolichol synthesis or recycling result in Congenital Disorders of Glycosylation (CDG), such as CDG-Im and CDG-Iq (Cantagrel et al., 2010, DOI: 10.1016/j.cell.2010.06.001). Furthermore, altered dolichol concentrations are observed in aging and neurodegenerative conditions like Alzheimer's disease, where the molecule accumulates in specific brain regions (Soderberg et al., 1992, DOI: 10.1111/j.1471-4159.1992.tb10971.x).

Other names

DolicholsLong-chain polyprenolDolichyl phosphateDol-P

Dolichol levels are modulated indirectly through the inhibition of HMG-CoA reductase in the mevalonate pathway by statins, which reduces the availability of farnesyl pyrophosphate precursors (Grünler et al., 1994). Tunicamycin blocks the function of dolichol by inhibiting the enzyme DPAGT1, preventing the transfer of N-acetylglucosamine-1-phosphate to dolichol phosphate (Buczkowska et al., 2015).