Isoprenoids metabolism

Isoprenes are the 5-C functional units (monomer) of a variety of naturally occurring compounds termed as terpenoids or isoprenoids. Terpenoids are used as precursors for production of sterols and steroids in animals. Some proteins have terpenoid moieties attached to them in order to boost their attachment to membranes. There are two different metabolic pathways exist in various organisms for the synthesis of isoprene units isopentenyl diphosphate and its isomer dimethylallyl diphosphate. They are mevalonate pathway and non-mevalonate (DOXP/MEP) pathway. The mevalonate pathway utilises acetyl-CoA as substrate and produces HMG-CoA and mevalonate as intermediates in the pathway. This pathway takes place in animals, plants and yeast. The non-mevalonate pathway utilises glyceraldehydes-3-phosphate and pyruvate as substrates. In addition to possessing mevalonate pathway, plants also possess chloroplast based non-mevalonate pathway.

 

The mevalonate pathway is experimentally proven to be absent in Plasmodium falciparum. In addition, the experiments with DOXP-dependent non-mevalonate pathway inhibitors such as fosmidomycin demonstrated the presence of this non-mevalonate pathway. This pathway has also been validated as an effective drug target. As in plants, this pathway also localises to the plastid, apicoplast [1]. The genes for the enzymes of mevalonate pathway are also absent in the genome, whereas the enzymes of non-mevalonate pathway are present and metabolic pathway was reconstructed in MPMP. The non-mevolate pathway of isoprenoid biosynthesis is also present in Toxoplasma gondii and Neospora caninum. The genes for all the enzymes of the non-mevalonate pathway are present in the genomes of Piroplasma species suggesting the presence of this apicoplast-based pathway. The enzymes for the mevalonate pathway are absent in these genomes.

 

Enzyme EC Number Gene id
1-deoxy-D-xylulose-5-phosphate reductoisomerase 1.1.1.267 TA14290
4-hydroxy-3-methylbut-2-enyl diphosphate reductase 1.17.1.2 TA17670
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase 1.17.7.1 TA14455
Ferredoxin reductase 1.18.1.2 TA09580
1-deoxy-D-xylulose 5-phosphate synthase 2.2.1.7 TA20470
4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase 2.7.1.148 TA14545
Pyruvate kinase 2.7.1.40 TA11540
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 2.7.7.60 TA02505
2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 4.6.1.12 TA04155
Triose phosphate isomerase 5.3.1.1 TA08590
Triose phosphate transporter none TA05100
PEP/Pi translocator none TA06475
Ferredoxin none TA17305

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Phosphoenolpyruvate Glycolysis Isopentenyl-PP Terpenoid metabolism
Glycerone-P Glycolysis Dimethylallyl-PP Terpenoid metabolism