The non-mevalonate pathway or 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway (MEP/DOXP pathway) of isoprenoid biosynthesis is an alternative metabolic pathway leading to the formation of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) that has been elucidated only recently.^[1]

Contents 1 Diversity of isoprenoid biosynthesis 2 Reactions 3 Inhibition 4 T cell activation 5 References

[edit] Diversity of isoprenoid biosynthesis

The classical mevalonate pathway or HMG-CoA reductase pathway is an important cellular metabolic pathway present in all higher eukaryotes and many bacteria. It is important for the production of IPP and DMAPP that serve as the basis for the biosynthesis of molecules used in processes as diverse as protein prenylation, cell membrane maintenance, hormones, protein anchoring and N-glycosylation.

In contrast to the classical mevalonate pathway of isoprenoid biosynthesis, plants and apicomplexan protozoa such as malaria parasites have the ability to produce their isoprenoids (terpenoids) using an alternative pathway, the non-mevalonate pathway, which takes place in their plastids.^[2] In addition, most bacteria including important pathogens such as Mycobacterium tuberculosis synthesize IPP and DMAPP via the non-mevalonate pathway.

[edit] Reactions

The reactions are as follows:^[3]

Reactants	Enzyme	Product
Pyruvate and glyceraldehyde 3-phosphate	DOXP synthase (Dxs)	1-Deoxy-D-xylulose 5-phosphate (DOXP)
DOXP	DOXP reductase (Dxr, IspC)	2-C-methylerythritol 4-phosphate (MEP)
MEP	4-diphosphocytidyl-2-C-methyl-D-erythritol synthase (YgbP, IspD)	4-diphosphocytidyl-2-C-methylerythritol (CDP-ME)
CDP-ME	4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (YchB, IspE)	4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-MEP)
CDP-MEP	2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (YgbB, IspF)	2-C-methyl-D-erythritol 2,4-cyclopyrophosphate (MEcPP)
MEcPP	HMB-PP synthase (GcpE, IspG)	(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP)
HMB-PP	HMB-PP reductase (LytB, IspH)	IPP and DMAPP

[edit] Inhibition

Fosmidomycin specifically inhibits DOXP reductoisomerase, a key enzyme in the non-mevalonate pathway, and therefore represents an attractive candidate as antibiotic or antimalarial drug.^[4]

[edit] T cell activation

The intermediate HMB-PP is the natural activator for human Vγ9/Vδ2 T cells, the major γδ T cell population in peripheral blood.^[5]

[edit] References

v • d • e Metabolism - non-mevalonate pathway enzymes DXP synthase - DXP reductoisomerase - 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase - 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase - 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase - 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase - 4-hydroxy-3-methylbut-2-enyl diphosphate reductase