Non-mevalonate pathway

The Methylerythritolphosphatweg, also MEP pathway or DOXP way is a pathway that leads to the synthesis of dimethylallyl pyrophosphate ( DMAPP ) and isopentenyl pyrophosphate (IPP ), two isoprenes. It occurs in the plastids of plants, various protozoa, bacteria and algae, and has also been described for the unicellular parasite Plasmodium falciparum. In many higher eukaryotes and some bacteria developed the synthesis of isoprene in the so-called Mevalonatbiosyntheseweg takes place.

The Methylerithritolphosphatweg was discovered by the research groups to Michel Rohmer and Duilio Arigoni. In the English literature, he is out under non- mevalonate pathway.

Biochemistry

The pathway starts with the combination of pyruvate and glyceraldehyde -3 -phosphate ( G3P ). This reaction is catalyzed an Desoxyxylulosephosphat synthase ( DXS, EC 2.2.1.7 ) under Kohlenstoffdioxidabspaltung, with 1 -deoxy- D- xylulose -5-phosphate ( DXP ) is formed. DXP is also the precursor for pyridoxal and Thiaminbiosynthese.

DXP is reduced by the DXP reductase ( DXR, EC 1.1.1.267 ) to 2C -methyl-D -erythritol 4-phosphate (MEP), wherein NADPH is oxidised to NADP . At MEP then cytidine diphosphate is a continuation (CDP ), which catalyzes a cytidine diphosphate - methylerythritol synthase (CMS, EC 4.6.1.12 ). This reaction is cytidine triphosphate (CTP ) consumed and pyrophosphate (PPi ) is cleaved. The resulting product, 4 - Phosphocytidyl -2C- methyl- D-erythritol (CDP -ME), under adenosine triphosphate ( ATP) to use 4 - diphosphocytidyl -2C- methyl- D-erythritol -2-P ( MEP CDP ) is phosphorylated, which catalyzes a cytidyl methyl - kinase ( CMK, EC 2.7.1.148 ).

The ensuing reaction is a cyclization, wherein the elimination of cytidine monophosphate ( CMP), a phosphoric acid ester is formed between C2 and C4. The reaction is catalyzed by the methyl - erythritol cyclo -diphosphate synthase (MCS, EC 4.6.1.12 ), is produced 2C -methyl-D -erythritol -2 ,4- cyclodiphosphate ( MEcPP ). Hydroxy -methyl- butenyl -diphosphate synthase (HDS, EC 1.17.7.1 ) then catalyzes the reaction to give (E )-4- hydroxy-3- methylbut -2- enyldiphosphat ( HMB- PP), and water, said two reduced ferredoxin act as a reducing agent. The ensuing enzyme catalyzes both the conversion to IPP as well DMAPP in a ratio of 5:1. The enzyme responsible for this is the IPP / DMAPP synthase (IDS, EC 1.17.1.2 ), it is NAD (P ) H oxidized and cleaved water.

Pharmacology

This metabolic pathway found in Plasmodium falciparum, the causative agent of malaria, instead. Therefore, he has also become a target for the development of pharmaceuticals for malaria. The most common drug that acts by blocking against the MEP pathway, is the fosmidomycin.