Biochemical and physiological characterization of monocarboxylate transporter protein(s) in schistosomes.

摘要

Organic acids are characteristic end-products of carbohydrate metabolism in parasitic helminths. Some of the accumulating end-products include lactate, acetate, propionate and volatile fatty acids. In schistosomes, the presence of glucose in the ambient medium triggers a switch from aerobic respiration, with CO2 and H2O as the end products, to homolactic fermentation. This event is associated with a 50-fold increase in glycolytic flux and the lactic acid produced. Since the pKa of lactic acid is 3.86, it will, by large proportion, exist in the ionized form under the physiological pH 7.4. This necessitates the presence of a lactate transporter protein across the plasma membrane to flux out the accumulating lactic acid. Indeed, many studies on this type of transporter have been carried out in various cell types. These transporters exhibit broad specificity for short-chain monocarboxylates such as lactate, pyruvate, beta-hydroxybutyrate and acetoacetate. In our present study we have characterized lactic acid secretion by the schistosomula and adult Schistosoma mansoni ex vivo in the presence and in the absence of lactic acid transporter protein inhibitors, alpha-cyano-4-hydroxycinnamic acid and phloretin. The organic anion transporter inhibitor probenecid also had a significant inhibitory effect on lactic acid transport in this parasite. We also found that an accumulating level (>10 mM) of lactic acid in the medium is toxic to the parasite. Additionally, we have carried out in vitro experiments using vesicles isolated from the parasite to study the kinetics of this transporter. These results demonstrate the presence of a monocarboxylate transporter activity in S. mansoni.