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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/14 09:43:55」(JST)

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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

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

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

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

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

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.

References

^ http://www3.interscience.wiley.com/cgi-bin/fulltext/118687026/PDFSTART
^ "J Gerontol A Biol Sci Med Sci. 2005 Jan;60(1):39-43".
^ "Edlund C, Söderberg M, Kristensson K. Neurochem Int, 1994 Jul,25(1), 35-8."
^ "Schenk, B.; Fernandez, F.; Waechter, C. J. Glycobiology, 2001, 11(5), 61R-70R."
^ 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

T. Chojnacki and G. Dallner (1988). "The biological role of dolichol". Biochem J. 251 (1): 1–9. PMC 1148956. PMID 3291859.

External links

Overview at Birkbeck, University of London

UpToDate Contents

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1. 高IgD症候群：病態生理 hyperimmunoglobulin d syndrome pathophysiology

English Journal

AglR is required for addition of the final mannose residue of the N-linked glycan decorating the Haloferax volcanii S-layer glycoprotein.

Kaminski L, Guan Z, Abu-Qarn M, Konrad Z, Eichler J.SourceDepartment of Life Sciences, Ben Gurion University of the Negev, Beersheva 84105, Israel.
Biochimica et biophysica acta.Biochim Biophys Acta.2012 Oct;1820(10):1664-70. Epub 2012 Jun 27.
BACKGROUND: Recent studies of Haloferax volcanii have begun to elucidate the steps of N-glycosylation in Archaea, where this universal post-translational modification remains poorly described. In Hfx. volcanii, a series of Agl proteins catalyzes the assembly and attachment of a N-linked pentasacchar
PMID 22750201

N-glycans in cell survival and death: Cross-talk between glycosyltransferases.

Banerjee DK.AbstractAsparagine-linked (N-linked) protein glycosylation is one of the most important protein modifications. N-glycans with "high mannose", "hybrid", or "complex" type sugar chains participate in a multitude of cellular processes. These include cell-cell/cell-matrix/receptor-ligand interaction, cell signaling/growth and differentiation, to name a few. Many diseases such as disorders of blood clotting, congenital disorder of glycosylation, diseases of blood vessels, cancer, neo-vascularization, i.e., angiogenesis essential for breast and other solid tumor progression and metastasis are associated with N-glycan expression. Biosynthesis of N-glycans requires multiple steps and multiple cellular compartments. Following transcription and translation the proteins migrate to the endoplasmic reticulum (ER) lumen to acquire glycan chain(s) with a defined glycoform, i.e., a tetradecasaccharide. These are further modified, i.e., edited in ER lumen and in Golgi prior to moving to their respective destinations. The tetradecasaccharide is pre-assembled on a poly-isoprenoid lipid called dolichol, and becomes an essential component of the supply chain. Therefore, dolichol cycle synthesizing the lipid-linked oligosaccharide (LLO) is a hallmark for all N-linked glycoproteins. It is expected that there is a great deal of cross-talk between the participating glycosyltransferases and any missed step would express defective N-glycans that could have fatal consequences. The positive impact of the structurally altered N-glycans could lead to discovery of an N-glycan signature for a disease and/or help developing glycotherapeutic treating cancer or other human diseases. The purpose of this review is to identify the gaps of N-glycan biology and help developing appropriate technology for biomedical applications. This article is part of a Special Issue entitled Glycoproteomics.
Biochimica et biophysica acta.Biochim Biophys Acta.2012 Sep;1820(9):1338-46. Epub 2012 Feb 3.
Asparagine-linked (N-linked) protein glycosylation is one of the most important protein modifications. N-glycans with "high mannose", "hybrid", or "complex" type sugar chains participate in a multitude of cellular processes. These include cell-cell/cell-matrix/receptor-ligand interaction, cell signa
PMID 22326428

Japanese Journal

Development of a Series of Gateway Binary Vectors Possessing a Tunicamycin Resistance Gene as a Marker for the Transformation of Arabidopsis thaliana

TANAKA Yuji,NAKAMURA Shinya,KAWAMUKAI Makoto,KOIZUMI Nozomu,NAKAGAWA Tsuyoshi
Bioscience, biotechnology, and biochemistry 75(4), 804-807, 2011-04-23
… We made two series of Gateway binary vectors, pGWBs and R4pGWBs, possessing a UDP-N-acetylglucosamine: dolichol phosphate N-acetylglucosamine-1-P transferase (GPT) gene driven by the nopaline synthase promoter (Pnos) as a tunicamycin resistance marker for the transformation of Arabidopsis thaliana. …
NAID 10028272038

臨床的意義のあるN-結合型糖鎖生合成の初期過程における新たな発見

竹内英之
Trends in glycoscience and glycotechnology 22(126), 311-313, 2010-11-30
NAID 10027893347

Related Pictures

★リンクテーブル★

リンク元	「ドリコール」
拡張検索	「dolichol monophosphate mannose」「dolichol diphosphate」

「ドリコール」

Dolichol (Data for n=20)
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 (77 °F), 100 kPa)
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	Infobox references

　　[★]

英: dolichol
関: テルペン、イソプレノイド

「dolichol monophosphate mannose」

　　[★]

ドリコールリン酸マンノース

「dolichol diphosphate」

　　[★] ドリコール二リン酸

[1] ttp://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."

[pmid19534648-5] 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.

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dolichol