Department of Biology, Colgate University, 13 Oak Dr., Hamilton, NY, 13346, USA.
Department of Mathematics, Colgate University, 13 Oak Dr., Hamilton, NY, 13346, USA.
Vet Res Commun. 2023 Jan;47(1):39-50. doi: 10.1007/s11259-022-09926-3. Epub 2022 Apr 19.
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 in plasma from 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.
动物通过氧化磷酸化利用氧气产生 ATP，但当氧气水平不足时，细胞能量也可以通过糖酵解获得。虽然较大体重的大多数哺乳动物寿命较长，但小型犬种往往比大型犬种寿命更长。先前已经表明，较大犬种的原代成纤维细胞在其整个生命周期中对糖酵解表型的依赖性增加。糖酵解酶丙酮酸激酶 (PK)、乳酸脱氢酶 (LDH) 和磷酸烯醇丙酮酸羧激酶 (PEPCK) 的不同活性水平可能为不同体型犬种随着年龄增长观察到的不同代谢表型提供机制方面的见解。在这项研究中，1) 我们测量了不同品种和年龄的犬原代成纤维细胞中 PK、LDH 和 PEPCK 的活性，2) 测量了不同品种和年龄的犬血浆中 PK 和 LDH 的活性。我们发现，原代成纤维细胞中 PK、LDH 和 PEPCK 的活性与体重之间没有显著关系。此外，与年轻犬相比，老年犬的这些酶活性没有显著差异。在血浆中，我们发现 PK 活性与体重呈负相关，而 LDH 活性与体重无关。LDH 活性与犬的年龄呈负相关。此外，虽然 PK 活性与年龄之间的负相关关系仅具有边缘意义，但最佳子集回归模型表明，年龄对 PK 活性具有显著的边际影响。PK 和 LDH 可能为小型犬的其他代谢途径提供中间产物。然而，大型犬种可能在 PK 水平上表现出代谢缺陷，这种细胞代谢途径可能有助于肿瘤的进展。
