| AutoignitionPt =
refers to any of a group of long-chain mostly unsaturated organic compound
s that are made up of varying numbers of isoprene
units terminating in an α-saturated isoprenoid group, containing an alcohol
Dolichols play a role in the co-translational modification of proteins known as N-glycosylation
in the form of dolichol phosphate
. Dolichols function as a membrane anchor for the formation of the oligosaccharide
Glc3-Man9-GlcNAc2 (where Glc is glucose
, Man is mannose
, and GlcNAc is N-acetylglucosamine
). This oligosaccharide is transferred from the dolichol donor onto certain asparagine
residues (onto a specific sequence that is "Asn-X-Ser/Thr") of newly forming polypeptide chains. Dolichol is also involved in transfer of the monosaccharides to the forming Glc3-Man9-GlcNAc2-Dolichol carrier.
In addition, dolichols can be adducted to protein
s as a posttranslational modification
, a process in which branched carbohydrate trees are formed on a dolichol moiety and then transferred to an assembly of proteins to form a large glycoprotein
in the rough endoplasmic reticulum
Dolichols are the major lipid component (14% by mass) of human substantia nigra (SN) neuromelanin
Dolichol phosphate was discovered at the University of Liverpool in the 1960s, although researchers did not know its function at the time of discovery.
Role in aging
Dolichol has been suggested to be used as a biomarker for aging
."J Gerontol A Biol Sci Med Sci. 2005 Jan;60(1):39-43". During aging, the human brain
shows a progressive increase in levels of dolichol, a reduction in levels of ubiquinone
, but relatively unchanged concentrations of cholesterol
and dolichyl phosphate. In the neurodegenerative disease Alzheimer's disease
, the situation is reversed, with decreased levels of dolichol and increased levels of ubiquinone
. The concentrations of dolichyl phosphate are also increased, while cholesterol
remains unchanged. This study link
shows that the isoprenoid
changes in Alzheimer's disease
differ from those occurring during normal aging, and, therefore, this disease cannot be regarded as a result of premature aging
. The increase in the sugar carrier dolichyl phosphate may reflect an increased rate of glycosylation
in the diseased brain, and the increase in the endogenous anti-oxidant ubiquinone
an attempt to protect the brain from oxidative stress
, for instance, induced by lipid peroxidation
."Edlund C, Söderberg M, Kristensson K. Neurochem Int, 1994 Jul,25(1), 35-8."
Dolichol is a product of the HMG-CoA reductase pathway
(also known as the mevalonate
pathway), and as such their creation and availability are affected by mevalonate inhibition
. First, a cis (or Z) -prenyltransferase catalyzes the condensation of farnesyl diphosphate
(FPP) with a varying number (dependent on the particular cis-prenyltransferase) of isopentenyl diphosphate (IPP) molecules, resulting in the formation of a 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 known as dolichol."Schenk, B.; Fernandez, F.; Waechter, C. J. Glycobiology
, 2001, 11(5), 61R-70R."
Dolichols are found in eukaryotes and in archaea, although similar polyprenol
s molecules are found in bacteria. Polyprenols in bacteria do not contain an α-saturated isoprenoid and are typically smaller in terms of isoprenoid units or carbon length. Polyprenols perform similar functions within bacteria; that is, they function as glycosyl carrier lipids involved in formation of complex branched polysaccharide. However, the cellular process they are involved in is not glycosylation, but instead cell wall biosynthesis. Statins decrease dolichol levels in the body.
The Australian pharmaceutical company Solagran
has been investigating the medical significance of polyprenol
s and their substitution with dolichols when ingested where there is a deficiency. Trials of Ropren (already pharmaceutically registered as a hepatoprotector) in relation to neurodegenerative diseases (including Alzheimer's disease) in both Russia link
and Australia link
indicate considerable potential as a safe and effective treatment.