Dolichol

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Dolichol (Data for n=20)
Structure of Dolichol. Data below is for 20 isoprene residues
Identifiers
CAS number 2067-66-5 YesY
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 (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

Dolichol refers to any of a group of long-chain mostly unsaturated organic compounds that are made up of varying numbers of isoprene units terminating in an α-saturated isoprenoid group, containing an alcohol functional group.

Functions[edit]

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 proteins 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.[1]

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[edit]

Dolichol has been suggested to be used as a biomarker for aging.[2] 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 [1] 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.[3]

Synthesis[edit]

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.[4]

Other[edit]

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 polysaccharide. However, the cellular process they are involved in is not glycosylation, but instead cell wall biosynthesis. Statins decrease dolichol levels in the body.[5]

Medical Significance[edit]

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 [2] and Australia [3] indicate considerable potential as a safe and effective treatment.

See also[edit]

References[edit]

  1. ^ http://www3.interscience.wiley.com/cgi-bin/fulltext/118687026/PDFSTART
  2. ^ "J Gerontol A Biol Sci Med Sci. 2005 Jan;60(1):39-43".
  3. ^ "Edlund C, Söderberg M, Kristensson K. Neurochem Int, 1994 Jul,25(1), 35-8."
  4. ^ "Schenk, B.; Fernandez, F.; Waechter, C. J. Glycobiology, 2001, 11(5), 61R-70R."
  5. ^ Bełtowski J, Wójcicka G, Jamroz-Wiśniewska A (September 2009). "Adverse effects of statins - mechanisms and consequences". Curr Drug Saf 4 (3): 209–28. doi:10.2174/157488609789006949. PMID 19534648. 

Bibliography[edit]

External links[edit]