(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate
history(''E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate''' (HMB-PP, HMBPP) or (''E)-4-hydroxy-dimethylallyl pyrophosphate''' (HDMAPP) is an intermediate of the non-mevalonate pathway of isoprenoid biosynthesis.Rohmer M. The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants. Nat Prod Rep. 1999;16:565–74. PMID 10584331Fox DT, Poulter CD. Synthesis of (E)-4-hydroxydimethylallyl diphosphate. An intermediate in the methyl erythritol phosphate branch of the isoprenoid pathway. J Org Chem. 2002;67:5009-10. PMID 12098326 The enzyme HMB-PP synthase (GcpE, IspG) catalyzes the conversion of 2-C-methyl-D-erythritol 2,4-cyclopyrophosphate (MEcPP) into HMB-PP, and 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.Eisenreich W, Bacher A, Arigoni D, Rohdich F. Biosynthesis of isoprenoids via the non-mevalonate pathway. Cell Mol Life Sci. 2004;61:1401–26. PMID 15197467
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 more potent than any other natural compound, such as IPP or alkyl amines.Eberl M, Hintz M, Reichenberg A, Kollas AK, Wiesner J, Jomaa H. Microbial isoprenoid biosynthesis and human γδ T cell activation. FEBS Lett. 2003;544:4–10. PMID 12782281