(''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.
The enzyme
HMB-PP synthase (GcpE, IspG) catalyzes the conversion of
2-''C''-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) into HMB-PP. HMB-PP is then converted further to
isopentenyl pyrophosphate
Isopentenyl pyrophosphate (IPP, isopentenyl diphosphate, or IDP) is an isoprenoid precursor. IPP is an intermediate in the classical, HMG-CoA reductase pathway (commonly called the mevalonate pathway) and in the ''non-mevalonate'' MEP pathway of i ...
(IPP) and
dimethylallyl pyrophosphate
Dimethylallyl pyrophosphate (DMAPP; or alternatively, dimethylallyl diphosphate (DMADP); also isoprenyl pyrophosphate) is an isoprenoid precursor. It is a product of both the mevalonate pathway and the MEP pathway of isoprenoid precursor biosynt ...
(DMAPP) by
HMB-PP reductase (LytB, IspH).
HMB-PP is an essential metabolite in most pathogenic bacteria including ''
Mycobacterium tuberculosis
''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis.
First discovered in 1882 by Robert Koch, ''M. tuberculosis'' ha ...
'' as well as in
malaria
Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
parasites, but is absent from the human host.
HMB-PP is the physiological activator ("
phosphoantigen 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 (''E'')-4-hydroxy-3-methyl-but-2-enyl pyrophosphate ( HMB-PP), a natural intermediate of the non-mev ...
") for human
Vγ9/Vδ2 T cells, the major
γδ T cell
Gamma delta T cells (γδ T cells) are T cells that have a γδ T-cell receptor (TCR) on their surface. Most T cells are αβ (alpha beta) T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, ...
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.
References
External links
*
{{DEFAULTSORT:Hydroxymethylbutenyl Pyrophosphate
Biomolecules
Metabolism
Pyrophosphate esters
Hemiterpenes