(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate

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(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate
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Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)

Infobox disclaimer and references

(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.[1][2] 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.[3]

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.[4]

References

  1. 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 10584331
  2. Fox 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
  3. 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
  4. 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

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