Riboflavin metabolism

Riboflavin, also known as vitamin B2 is an important component of the cofactors FAD and FMN. These cofactors form part of flavoproteins and essential for many metabolic pathways including fatty acid metabolism, citrate cycle and electron transport chain. FAD is a crucial electron acceptor in addition to NAD+ and NADP+ in these pathways. The apicomplexans Plasmodium falciparum, Toxoplasma gondii and Neospora caninum do not possess the metabolic ability to synthesise riboflavin de novo and therefore the enzymes involved in synthesis of riboflavin from GTP and ribulose 5-phosphate are absent in both genomes. These species salvage riboflavin from host and generate FMN and FAD de novo as these possess the enzymes riboflavin kinase and FAD synthase. Although depletion of riboflavin in growth medium has not resulted in any inhibition of growth of P. falciparum parasites cultured with erythrocytes, the in vivo studies showed the association of riboflavin deficiency with adverse effects in parasite growth. It may suggest that the stores of riboflavin in erythrocytes is sufficient to supplement the parasites [1]. A clinical study of malaria-infected children with riboflavin deficiency pointed out that the parasite count is lower in these children compared to children with riboflavin in normal range, although the riboflavin-deficient children recovered slower [2]. In contrast, a recent study by Akompong et al demonstrated that the treatment of infected erythrocyte cells with riboflavin for 24 hours resulting in reduction in parasite levels of oxidised haemoglobin by 55%, hemozoin by 50% and size of food vacuole by 47%. In addition, treating for 48 hours has resulted in further reduction in food vacuole size and inhibition of asexual Plasmodium growth [3]. This may suggest the toxicity of higher concentrations of flavins in P. falciparum and further studies need to be conducted in order to understand the role of riboflavin in apicomplexan metabolism and growth. The transporters which are involved in the transport of riboflavin through parasite membranes are not yet identified in both P. falciparum and Coccidia genomes.

 

Enzyme EC Number Gene id
Riboflavin kinase 2.7.1.26 NCLIV_059550
FAD synthetase 2.7.7.2 NCLIV_051520
Acid phosphatase 3.1.3.2 NCLIV_005880
Acid phosphatase 3.1.3.2 NCLIV_019880

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Riboflavin Host FMN/FAD Many metabolic pathways