Thiamine salvage

Thiamine pyrophosphate is the metabolically active form thiamine, also known as vitamin B1. Thiamine pyrophosphate is an important cofactor of enzymes of carbohydrate and amino acid metabolism such as pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase, pyruvate decarboxylase and dihydrolipoamide dehydrogenase. Plants, bacteria and fungi can synthesise thiamine, whereas mammals salvage it from diet. Mammals possess the enzyme which catalyses pyro-phosphorylation of thiamine to thiamine pyrophosphate, thiamine diphosphokinase (TPK). Plasmodium falciparum can synthesise Thiamine phosphate (TMP) from 4-methyl-5-(2-phosphoethyl)-thiazole (THZ-P) and 4-amino-2-methyl-5-hydroxymethyl pyrimidine diphosphate (HMP-PP) by the action of the enzymes THZ kinase (ThiM), HMP/HMP-kinase (ThiD) and thiamine phosphate synthase (ThiE) in addition to salvaging thiamine from host (thiamine metabolism). The analysis of Toxoplasma gondii and Neospora caninum gene models shows the absence of the enzymes catalysing de novo thiamine biosynthesis. As in mammals, it possesses the enzyme TPK and it can catalyse pyro-phosphorylation of thiamine salvaged from host to thiamine pyrophosphate, the active form of vitamin B1. The transporters involved in uptake of thiamine across parasite plasma membrane and translocation of active TPP across organellar membranes are not yet identified in T. gondii, N. caninum and P. falciparum.

 

Enzyme EC Number Gene id
Thiamine diphosphokinase 2.7.6.2 NCLIV_052210

 

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Thiamine pyrophosphate dependent enzymes in N. caninum genome

 

Enzyme EC Number Gene id
Pyruvate dehydrogenase E1 beta subunit 1.2.4.1 NCLIV_034990
Pyruvate dehydrogenase E1 alpha subunit 1.2.4.1 NCLIV_062940
2-Oxoglutarate dehydrogenase E1 subunit 1.2.4.2 NCLIV_018800
Branched-chain a-keto-acid dehydrogenase E1 alpha chain 1.2.4.4 NCLIV_012850
Branched-chain a-keto-acid dehydrogenase E1 alpha chain 1.2.4.4 NCLIV_016110
Branched-chain a-keto-acid dehydrogenase E1 beta chain 1.2.4.4 NCLIV_057460
Transketolase 2.2.1.1 NCLIV_011210