D-lactate production in erythrocytes infected with Plasmodium falciparum.

The production of D-lactate that accompanies the metabolism of glucose to L-lactate in Plasmodium falciparum was evaluated with erythrocytes that contained either young or mature parasites. Infected cells with ring-stage parasites release L-lactate and D-lactate at rates 1340 and 81 nmol h-1 (10(8) cells)-1, respectively. These rates increase to 2050 and 136 nmol h-1 (10(8) cells)-1, respectively, in infected cells with trophozoite/schizont-stage parasites. D-Lactate represents 6-7% of the total lactate. The formation of D-lactate is by way of a methylgloxal pathway in which methylglyoxal is formed nonenzymatically from dihydroxyacetone phosphate and is then converted into D-lactate by the sequential action of parasite glycoxalase I and glyoxalase II. The kinetic properties of parasite glyoxalase I and glyoxalase II allow these enzymes to be distinguished from those in the host cell. D-Lactate production by the parasite appears to be a defense mechanism to protect the parasite from the toxic effects of methylglyoxal.