Scaling with body mass and age in glycolytic enzymes of domestic dogs.

Abstract

Animals produce ATP through oxidative phosphorylation using oxygen, but cellular energy can also be obtained through glycolysis when oxygen is not present at sufficient levels. Although most mammals of larger body mass have longer life spans, small dog breeds tend to outlive large breeds. Primary fibroblast cells from larger breeds of dogs have previously been shown to have increased dependency on glycolytic phenotypes across their lifespan. Different levels of activity of the glycolytic enzymes pyruvate kinase (PK), lactate dehydrogenase (LDH), and phosphoenolpyruvate carboxykinase (PEPCK) may provide insight to a mechanism that leads to the different metabolic phenotype observed in different sized breeds as they age. In this study, 1) we measured the activities of PK, LDH, and PEPCK in primary fibroblasts from dogs of different breed sizes and age classes and 2) measured the activities of PK and LDH inplasmafrom dogs of different breed sizes and age classes. We found that there was no significant relationship between body mass and PK, LDH and PEPCK activity in primary fibroblasts. Further, there were not significant differences with activity in these enzymes for old dogs compared to young dogs. In plasma, we found a negative correlation between PK activity and body mass and no relationship between LDH activity and body mass. There was a negative relationship between LDH activity and age in dogs. Further, while a negative correlational relationship between PK activity and age was only marginal, a best subsets regression model demonstrated a significant marginal effect of age on PK activity. PK and LDH may provide intermediates for other metabolic pathways in small breeds. However, large breed dogs may demonstrate a deficiency in metabolism at the PK level, a cellular metabolic pathway that may potentially aid in tumor progression.