{{DISPLAYTITLE:(''E'')-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate}} {{chembox | verifiedrevid = 477199926 | Name=(''E'')-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate | ImageFile = HMB-PP.svg | ImageSize = 190px | ImageName = Chemical structure of HMB-PP | ImageFile1 = HMBPP-3D-balls.png | ImageSize1 = 240px | ImageName1 = Ball-and-stick model, shown here as a 3- ion | PIN = (2''E'')-4-Hydroxy-3-methylbut-2-en-1-yl trihydrogen diphosphate | OtherNames = (''E'')-4-hydroxy-dimethylallyl pyrophosphate<br />HDMAPP<br />(''E'')-4-Hydroxy-3-methyl-but-2-enyl diphosphate<br />HMBDP |Section1={{Chembox Identifiers | CASNo = 396726-03-7 | CASNo_Ref = {{Cascite|changed|ChemSpider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 15664 | ChemSpiderID = 4445244 | InChI = 1/C5H12O8P2/c1-5(4-6)2-3-12-15(10,11)13-14(7,8)9/h2,6H,3-4H2,1H3,(H,10,11)(H2,7,8,9)/b5-2+ | InChIKey = MDSIZRKJVDMQOQ-GORDUTHDBB | SMILES1 = O=P(OP(=O)(O)O)(OC/C=C(/CO)C)O | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C5H12O8P2/c1-5(4-6)2-3-12-15(10,11)13-14(7,8)9/h2,6H,3-4H2,1H3,(H,10,11)(H2,7,8,9)/b5-2+ | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = MDSIZRKJVDMQOQ-GORDUTHDSA-N | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 145233 | PubChem = 21597501 | SMILES = CC(=CCOP(=O)([O-])OP(=O)([O-])[O-])CO}} |Section2={{Chembox Properties | C=5 | H=12 | O=8 | P=2 | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = }} |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} }}
'''(''E'')-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate''' ('''HMBPP''' or '''HMB-PP''') is an intermediate of the MEP pathway (non-mevalonate pathway) of isoprenoid biosynthesis.<ref name="Rohmer">{{cite journal | last1 = Rohmer | first1 = M | title = The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants | journal = Natural Product Reports | volume = 16 | issue = 5 | pages = 565–74 | year = 1999 | pmid = 10584331 | doi=10.1039/a709175c | last2 = Rohmer | first2 = Michel}}</ref><ref name="Poulter">{{cite journal | last1 = Fox | first1 = DT | last2 = Poulter | first2 = CD | title = Synthesis of (E)-4-hydroxydimethylallyl diphosphate. An intermediate in the methyl erythritol phosphate branch of the isoprenoid pathway | journal = The Journal of Organic Chemistry | volume = 67 | issue = 14 | pages = 5009–10 | year = 2002 | pmid = 12098326 | doi=10.1021/jo0258453}}</ref> The enzyme HMB-PP synthase (GcpE, IspG) catalyzes the conversion of 2-''C''-methyl-<small>D</small>-erythritol 2,4-cyclodiphosphate (MEcPP) into HMB-PP. HMB-PP is then converted further to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) by HMB-PP reductase (LytB, IspH).
HMB-PP is an essential metabolite in most pathogenic bacteria including ''Mycobacterium tuberculosis'' as well as in malaria parasites, but is absent from the human host.<ref name="Eisenreich">{{cite journal | last1 = Eisenreich | first1 = W | last2 = Bacher | first2 = A | last3 = Arigoni | first3 = D | last4 = Rohdich | first4 = F | title = Biosynthesis of isoprenoids via the non-mevalonate pathway | journal = Cellular and Molecular Life Sciences | volume = 61 | issue = 12 | pages = 1401–26 | year = 2004 | pmid = 15197467 | doi = 10.1007/s00018-004-3381-z | s2cid = 24558920 | pmc = 11138651 }}</ref>
HMB-PP is the physiological activator ("phosphoantigen") for human Vγ9/Vδ2 T cells, the major γδ T cell population in peripheral blood. With a bioactivity of 0.1 nM it is 10,000-10,000,000 times more potent than any other natural compound, such as IPP or alkyl amines. HMB-PP functions in this capacity by binding the B30.2 domain of BTN3A1.<ref>{{Cite journal|title = Activation of human γδ T cells by cytosolic interactions of BTN3A1 with soluble phosphoantigens and the cytoskeletal adaptor Periplakin|vauthors=Rhodes DA, Chen HC, Price AJ, Keeble AH, Davey MS, James LC, Eberl M, Trowsdale J|date = 2015|journal = J Immunol|doi = 10.4049/jimmunol.1401064|pmid = 25637025|pmc=4337483|volume=194|issue=5|pages=2390–8}}</ref>
==References== {{reflist}}
==External links== * {{MeshName|4-hydroxy-3-methylbut-2-enyl+pyrophosphate}}
{{Cholesterol metabolism intermediates}}
{{DEFAULTSORT:Hydroxymethylbutenyl Pyrophosphate}} Category:Biomolecules Category:Metabolism Category:Pyrophosphate esters Category:Hemiterpenes