Impaired Activity of Alpha-Ketoglutarate Dehydrogenase of Heart Mitochondria in Chronic Renal Failure: Role of Secondary Hyperparathyroidism

Abstract

Chronic renal failure (CRF) is associated with impaired oxidation of alpha-ketoglutarate (alpha-KG) by heart mitochondria, and previous data indicated that this derangement is due to the state of secondary hyperparathyroidism of CRF. A reduction in the utilization of alpha-KG by heart mitochondria implies that the activity of mitochondrial alpha-ketoglutarate dehydrogenase (alpha-KGDH) is impaired; however, direct evidence for such an abnormality is not available. We examined the Vmax and the Km of alpha-KGHD of heart mitochondria obtained from normal rats, CRF animals and normocalcemic parathyroidectomized (PTX) CRF rats. Our data showed that CRF has no effect on the Km of alpha-KGDH for alpha-KG. However, Vmax of the enzyme was significantly (p less than 0.01) reduced and this abnormality was prevented by PTX of CRF rats. Our results provide the evidence that the impaired utilization of alpha-KG by myocardial mitochondria of CRF rats is due to reduced Vmax of alpha-KGDH and that both derangements are mediated by excess PTH or a metabolic consequence of the secondary hyperparathyroidism of CRF.