Cobalamin and folate metabolism in helminths

Abstract

Knowledge about the source, metabolism and functions of cobalamins and folates in helminths remains fragmentary. It is likely that all helminths, whether free-living or parasitic, cannot synthesize cobalamins and folates de novo. Folates, but not cobalamins, appear to be ubiquitous in helminths. Of the parasitic helminths that take up free cobalamins in vitro, all but one species showed no uptake of cobalamin bound to transport proteins, although the latter type of cobalamin by far predominates in vivo. Certain free-living and parasitic helminths in vitro and in vivo took up a variety of folyl and antifolyl monoglutamates, but it is not known whether helminths can take up any folyl polyglutamates. Helminths that have any folate-dependent metabolism appear able to produce polyglutamylated forms of the required tetrahydrofolate coenzymes. Helminths that possess a functional cobalamin-dependent pathway from succinyl CoA to propionyl CoA appear able to form the required adenosylcobalamin coenzyme. Only free-living helminths may possess a cobalamin (and 5-methyltetrahydrofolate)-dependent pathway from homocysteine to methionine. It is likely that all helminths possess the 5,10-methylenetetrahydrofolate-dependent pathway from deoxyuridylate to thymidylate. All helminths appear able to salvage purine bases and nucleosides, but 10-formyltetrahydrofolate-dependent de novo purine ribonucleotide synthesis has been demonstrated unequivocally only in nematodes. The primitive parasitic groups of helminths exhibit cobalamin metabolism, whereas the more highly evolved ones seem to have lost the mechanisms for uptake and the associated biochemical pathways utilizing cobalamins.