(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate
Encyclopedia
-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP or HMB-PP) is an intermediate of the non-mevalonate pathway
Non-mevalonate pathway
The non-mevalonate pathway or 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis is an alternative metabolic pathway leading to the formation of isopentenyl pyrophosphate and dimethylallyl pyrophosphate that has been elucidated only...

 of isoprenoid biosynthesis. 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
Isopentenyl pyrophosphate
Isopentenyl pyrophosphate is an intermediate in the classical, HMG-CoA reductase pathway used by organisms in the biosynthesis of terpenes and terpenoids. IPP is formed from acetyl-CoA via mevalonic acid...

 (IPP) and dimethylallyl pyrophosphate
Dimethylallyl pyrophosphate
Dimethylallyl pyrophosphate is an intermediate product of both mevalonic acid pathway and DOXP/MEP pathway. It is an isomer of isopentenyl pyrophosphate and exists in virtually all life forms...

 (DMAPP) by HMB-PP reductase (LytB, IspH).

HMB-PP is an essential metabolite in most pathogenic bacteria including Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

as well as in malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...

 parasites, but is absent from the human host.

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
Non-peptidic antigen
Non-peptidic antigens are low-molecular-weight compounds that stimulate human Vγ9/Vδ2 T cells. The most potent activator for Vγ9/Vδ2 T cells is -4-hydroxy-3-methyl-but-2-enyl pyrophosphate , a natural intermediate of the non-mevalonate pathway of isopentenyl pyrophosphate biosynthesis...

.

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