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{{Short description|Group of long-chain unsaturated lipids}} |
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{{chembox |
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{{chembox |
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| verifiedrevid = 404252796 |
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| verifiedrevid = 407688731 |
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| ImageFile=Doichol.png |
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|Name=Dolichol <small>(Data for n=20)</small> |
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| ImageName = Structure of Dolichol. |
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|ImageFile=Doichol.png |
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|ImageName = Structure of Dolichol. Data below is for 20 isoprene residues |
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|Section1={{Chembox Identifiers |
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|OtherNames= |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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|Section1= {{Chembox Identifiers |
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| CASNo=2067-66-5 |
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| CASNo=11029-02-0 |
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| CASNo1 = 2067-66-5 |
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| PubChem=6433320 |
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| index1_label = (dolichol-20) |
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| ChemSpiderID1 = 4938490 |
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| MeSHName=Dolichol |
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| PubChem=6433320 |
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| InChI1=1S/C100H164O/c1-81(2)41-22-42-82(3)43-23-44-83(4)45-24-46-84(5)47-25-48-85(6)49-26-50-86(7)51-27-52-87(8)53-28-54-88(9)55-29-56-89(10)57-30-58-90(11)59-31-60-91(12)61-32-62-92(13)63-33-64-93(14)65-34-66-94(15)67-35-68-95(16)69-36-70-96(17)71-37-72-97(18)73-38-74-98(19)75-39-76-99(20)77-40-78-100(21)79-80-101/h41,43,45,47,49,51,53,55,57,59,61,63,65,67,69,71,73,75,77,100-101H,22-40,42,44,46,48,50,52,54,56,58,60,62,64,66,68,70,72,74,76,78-80H2,1-21H3/b82-43+,83-45+,84-47+,85-49+,86-51-,87-53+,88-55+,89-57+,90-59+,91-61+,92-63+,93-65+,94-67+,95-69-,96-71+,97-73+,98-75+,99-77+ |
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| InChIKey1 = KEVPZUBEAUSPNJ-OYHKHEHLSA-N |
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| SMILES1=CC(CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(/C)\CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(/C)\CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CCC=C(C)C)CCO |
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| KEGG = C00381 |
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| ChEBI = 16091 |
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| MeSHName=Dolichol |
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|Section2= {{Chembox Properties |
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|Section2={{Chembox Properties |
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| Formula=C<sub>100</sub>H<sub>164</sub>O |
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| Formula=Variable<br />Dolichol-20: C<sub>100</sub>H<sub>164</sub>O |
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| MolarMass=1382.37 |
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| MolarMass=Variable<br />Dolichol-20: 1382.37 g/mol |
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|Section3= {{Chembox Hazards |
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|Section3={{Chembox Hazards |
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'''Dolichol''' refers to any of a group of long-chain mostly ] ]s that are made up of varying numbers of ] units terminating in an α-saturated isoprenoid group, containing an ] functional group. |
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'''Dolichol''' refers to any of a group of long-chain mostly ] ]s that are made up of varying numbers of ] units terminating in an α-saturated isoprenoid group, containing an ] functional group. |
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==Functions== |
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==Functions== |
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Dolichols play a role the co-translational modification of proteins known as ] in the form of dolichol ]. Dolichols function as a membrane anchor for the formation of the ] Glc3-Man9-GlcNAc2 (where Glc is ], Man is ], and GlcNAc is ]). This oligosaccharide is transferred from the dolichol donor onto certain ] residues of newly forming polypeptide chains. Dolichol is also involved in transfer of the monosaccharides to the forming Glc3-Man9-GlcNAc2-Dolichol carrier. |
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Dolichols play a role in the ] of proteins known as ] in the form of ]. Dolichols function as a membrane anchor for the formation of the ] Glc<sub>3</sub>–Man<sub>9</sub>–GlcNAc<sub>2</sub> (where Glc is ], Man is ], and GlcNAc is ]). This oligosaccharide is transferred from the dolichol donor onto certain ] 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 Glc<sub>3</sub>–Man<sub>9</sub>–GlcNAc<sub>2</sub>–Dolichol carrier. |
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In addition, dolichols can be adducted to ]s as a ], 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 ] in the ]. |
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In addition, dolichols can be adducted to ]s as a ], 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 ] in the ]. |
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Dolichols are the major lipid component (14% by mass) of human substantia nigra (SN) ].<ref>{{cite journal|last1=Fedorow|first1=Heidi|last2=Pickford|first2=Russell|last3=Hook|first3=James M.|last4=Double|first4=Kay L.|last5=Halliday|first5=Glenda M.|last6=Gerlach|first6=Manfred|last7=Riederer|first7=Peter|last8=Garner|first8=Brett|title=Dolichol is the major lipid component of human substantia nigra neuromelanin|journal=Journal of Neurochemistry|date=February 2005|volume=92|issue=4|pages=990–995|doi=10.1111/j.1471-4159.2004.02975.x|pmid=15686500|doi-access=free}}</ref> |
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Dolichols are the major lipid component (14% by mass) of human substantia nigra (SN) ].<ref>http://www3.interscience.wiley.com/cgi-bin/fulltext/118687026/PDFSTART</ref> |
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Dolichol phosphate was discovered at the University of Liverpool in the 1960s, although researchers did not know its function at the time of discovery.<ref>{{cite journal|last1=Chojnacki|first1=T|last2=Dallner|first2=G|title=The biological role of dolichol.|journal=The Biochemical Journal|date=1 April 1988|volume=251|issue=1|pages=1–9|pmid=3291859|doi=10.1042/bj2510001|pmc=1148956}}</ref> |
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==Role in aging== |
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==Role in aging== |
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Dolichol has been suggested to be used as a ] for aging.<ref>"J Gerontol A Biol Sci Med Sci. 2005 Jan;60(1):39-43".</ref> During aging, the ] shows a progressive increase in levels of dolichol, a reduction in levels of ], but relatively unchanged concentrations of ] and dolichyl phosphate. In the ] ], the situation is reversed, with decreased levels of dolichol and increased levels of ]. The concentrations of dolichyl phosphate are also increased, while ] remains unchanged. This study shows that the ] changes in ] differ from those occurring during normal aging, and, therefore, this disease cannot be regarded as a result of ]. The increase in the sugar carrier dolichyl phosphate may reflect an increased rate of ] in the diseased brain, and the increase in the endogenous ] ] an attempt to protect the brain from ], for instance, induced by ].<ref>"Edlund C, Söderberg M, Kristensson K. Neurochem Int, 1994 Jul,25(1), 35-8."</ref> |
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Dolichol has been suggested to be used as a ].<ref>"J Gerontol A Biol Sci Med Sci. 2005 Jan;60(1):39-43".</ref> During aging, the ] shows a progressive increase in levels of dolichol, a reduction in levels of ], but relatively unchanged concentrations of ] and dolichyl phosphate. In the ] ], the situation is reversed, with decreased levels of dolichol and increased levels of ubiquinone. The concentrations of dolichyl phosphate are also increased, while ] remains unchanged. The ] changes in Alzheimer's disease differ from those occurring during normal aging, and, therefore, this disease cannot be regarded as a result of ].<ref>{{Cite journal | journal = Neurochem. Int. | date = 1994 | volume = 25 | issue = 1 | pages = 35–38 | title = Isoprenoids in aging and neurodegeneration | author = Edlund C, Söderberg M, Kristensson K | doi = 10.1016/0197-0186(94)90050-7 | pmid = 7950967| s2cid = 34009482 }}</ref> The increase in the sugar carrier dolichyl phosphate may reflect an increased rate of ] in the diseased brain, and the increase in the endogenous ] ubiquinone an attempt to protect the brain from ], for instance, induced by ].<ref>Edlund C, Söderberg M, Kristensson K. Neurochem Int, 1994 Jul,25(1), 35-8</ref> |
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==Synthesis== |
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==Synthesis== |
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Dolichol is a product of the ] (also known as the ] pathway), and as such their creation and availability are affected by ]. First, a cis (or Z) -prenyltransferase catalyzes the condensation of ] (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.<ref>"Schenk, B.; Fernandez, F.; Waechter, C. J. Glycobiology, 2001, 11(5), 61R-70R."</ref> |
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Dolichol is a product of the ] (also known as the ] pathway), and as such their creation and availability are affected by ]. First, a cis (or Z) -prenyltransferase (]) catalyzes the condensation of ] (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). Lastly, the α isoprenoid unit is saturated by α-saturase (still a hypothetical enzyme), and this α-saturated polyprenyl alcohol is known as dolichol.<ref>Schenk, B.; Fernandez, F.; Waechter, C. J. ''Glycobiology'', 2001, 11(5), 61R-70R.</ref> |
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== Other == |
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== Other == |
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Dolichols are found in eukaryotes, although similar ]s molecules are found in other organisms including bacteria. ]s in bacteria do not contain an α-saturated isoprenoid and are typically smaller in terms of isoprenoid units or carbon length. ]s perform similar functions within bacteria; that is, they function as glycosyl carrier lipids involved in formation of complex branched polysacharide. However, the cellular process they are involved in is not glycosylation, but instead cell wall biosynthesis . |
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Dolichols are found in eukaryotes and in archaea,<ref>{{Cite journal |last1=Meyer |first1=Benjamin H. |last2=Albers |first2=Sonja-Verena |author-link2=Sonja-Verena Albers |date=2013-02-01 |title=Hot and sweet: protein glycosylation in Crenarchaeota |journal=Biochemical Society Transactions |language=en |volume=41 |issue=1 |pages=384–392 |doi=10.1042/BST20120296 |issn=0300-5127 |pmid=23356316}}</ref> although similar ]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.<ref name="pmid19534648">{{cite journal |vauthors=Bełtowski J, Wójcicka G, Jamroz-Wiśniewska A |title=Adverse effects of statins - mechanisms and consequences |journal=Curr Drug Saf |volume=4 |issue=3 |pages=209–28 |date=September 2009 |pmid=19534648 |doi=10.2174/157488609789006949 |url=http://www.benthamdirect.org/pages/content.php?CDS/2009/00000004/00000003/0009CDS.SGM |url-status=dead |archive-url=https://web.archive.org/web/20131029190654/http://www.benthamdirect.org/pages/content.php?CDS%2F2009%2F00000004%2F00000003%2F0009CDS.SGM |archive-date=2013-10-29 }}</ref> |
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==Medical Significance== |
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==Medical significance== |
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The Australian pharmaceutical company ] has been investigating the medical significance of ]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 and Australia indicate considerable potential as a safe and effective treatment. |
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The Australian pharmaceutical company Solagran has been investigating the medical significance of ]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<ref> 20 September 2005.</ref> and Australia<ref> 21 February 2007.</ref> indicate considerable potential as a safe and effective treatment. |
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==See also== |
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==See also== |
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== References == |
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== References == |
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{{Reflist|30em}} |
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<references/> |
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==External links== |
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