Differences in intermediary energy metabolism between juvenile and adult Fasciola hepatica

Abstract

A comparison of glucose catabolism by juvenile and adult liver flukes, Fasciola hepatica, showed that in the adult the cytosolic degradation of glucose via phosphoenolpyruvate carboxykinase (PEPCK) was the most important route, whereas in the freshly excysted juvenile a large part was degraded via pyruvate kinase (PK). However, it was also shown that the adult did not exclusively use the PEPCK pathway, nor did the juvenile exclusively use the PK pathway. When the juvenile was forced to anaerobic functioning it produced propionate and acetate just like the adult, but this did not imply that it switched to the pathways of the adult: the pathway via PK remained important. Malic enzyme (NADP(H)-dependent) was demonstrated to be present in the cytosol and in the mitochondria of both juveniles and adults. These enzyme activities enable the parasite to use a mixture of malate and pyruvate in any ratio as substrate for the mitochondrial production of proportionate and acetate. Pyruvate dismutation was important in the anaerobically functioning juvenile, whereas in the adult malate was the major, but not the only mitochondrial substrate. The pH profiles of PK and PEPCK showed that the pathway of PEP metabolism at the PK/PEPCK branchpoint can be regulated by the pH. However, the end products of glucose breakdown were not dependent on the pH. During its development, the liver fluke will gradually be forced to anaerobic functioning. At first, the acidic end product will favour a partitioning of PEP at the PK/PEPCK branchpoint toward malate formation. Later, a lasting predominance of the PEPCK pathway occurs as PK activity almost completely disappears. During the development of F. hepatica also a transition in the mitochondria occurs: at the acetyl-coenzyme A branchpoint a switch from citrate to acetate formation could be demonstrated. The most likely mechanism of this change is discussed.