Heme salvage and degradation

Porphyrins are organic aromatic compounds composed of four pyrrole rings interconnected to each other and to the Fe2+ ion. Porphyrins are essential cofactors of many proteins including cytochrome proteins and haemoglobin and myoglobin in humans. The first step in the production of porphyrin in animals is the mitochondrial formation of delta-aminolevulinate from glycine and succinyl-CoA. In humans, this aminolevulinate is then transported to cytosol where the 4-step conversion into Coproporphyrinogen III occurs. The remaining processing of this intermediate to protoporphyrin IX and then to heme takes place in mitochondrion.

 

The cytochrome proteins in Plasmodium falciparum and Toxoplasma gondii require de novo synthesis of porphyrin. Although P. falciparum obtains heme from host haemoglobin digestion, it cannot utilise them for biosynthesis of its own porphyrin-containing proteins [1] and converts them to hemozoin [2]. The orthologs of the enzymes of de novo heme biosynthesis in P. falciparum and T. gondii are absent in Theileria and Babesia genomes. The only enzyme present in the gene models of Babesia bovis is aminolevulinate dehydratase, the enzyme catalysing the second step of the pathway. This enzyme is absent in Theileria genomes. B. bovis digest haemoglobin and can crystallise heme to the disposal product, hemozoin as in P. falciparum [3]. In addition, heme oxygenase enzyme present in P. falciparum and absent in T. gondii is also present in Piroplasma genomes suggesting the presence of alternative route of heme disposal.

 

Enzyme EC Number Gene id
Heme oxygenase 1.4.99.3 TA06150
Cytochrome c heme lyase 4.4.1.17 TA06210
Cytochrome c heme lyase 4.4.1.17 TA15105
Cytochrome c none TA12950

 

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Examples of other heme containing proteins in Theileria annulata genome

 

Enzyme EC Number Gene id
Guanylyl cyclase beta 4.6.1.2 TA15475
Cytochrome c1 none TA08150
Cytochrome c2 precursor none TA10380