Dolichol
Identifiers
CAS number	2067-66-5
PubChem	6433320
MeSH	Dolichol
Properties
Molecular formula	C100H164O
Molar mass	1382.37
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

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.

Contents 1 Functions 2 Role in aging 3 Synthesis 4 Other 5 Medical Significance 6 See also 7 References 8 External links

[edit] Functions

Dolichols play a role 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 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 proteins as a posttranslational modification, a process whereby branched carbohydrate trees are formed on a dolichol moiety and then transferred to a an assembly of proteins to form a large glycoprotein in the rough endoplasmic reticulum.

[edit] Role in aging

Dolichol accumulates in tissues over time. Dolichols are the major lipid component (14% by mass) of human substantia nigra (SN) neuromelanin [1].

Dolichol has been suggested to be used as a biomarker for aging ^[1]. 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 a 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[2] shows that the isoprenoid changes in Alzheimer's disease differ from those occurring during normal aging and therefore this disease can not 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.^[2]

[edit] Synthesis

Dolichol is a product of the HMG-CoA reductase pathway (also known as the mevalonate pathway). 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 diphoshate (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. ^[3]

[edit] Other

Dolichols are found in eukaryotes, although similar polyprenols molecules are found in other organisms including 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 polysacharide. Although, the cellular process they are involved in is not glycosylation, but instead cell wall biosynthesis .

[edit] Medical Significance

The Australian pharmaceutical company Solagran has been investigating the medical significance of polyprenols 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 [3] and Australia [4] indicate considerable potential as a safe and effective treatment.

[edit] See also

• Dolichol kinase
• Polyprenols
• Solagran

[edit] References

1. ^ "J Gerontol A Biol Sci Med Sci. 2005 Jan;60(1):39-43".
2. ^ "Edlund C, Söderberg M, Kristensson K. Neurochem Int, 1994 Jul,25(1), 35-8."
3. ^ "Schenk, B.; Fernandez, F.; Waechter, C. J. Glycobiology, 2001, 11(5), 61R-70R."

[edit] External links

• Overview at Birkbeck, University of London