Impaired activity of alpha-ketoglutarate dehydrogenase of heart mitochondria in chronic renal failure: Role of secondary hyperparathyroidism

Chronic renal failure (CRF) is associated with impaired oxidation of α-ketoglutarate (α-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 α-KG by heart mitochondria implies that the activity of mitochondrial α-ketoglutarate dehydrogenase (α-KGDH) is impaired; however, direct evidence for such an abnormality is not available. We examined the V(max) and the K(m) of α-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 K(m) of α-KGDH for α-KG. However, V(max) of the enzyme was significantly (p < 0.01) reduced and this abnormality was prevented by PTX of CRF rats. Our results provide the evidence that the impaired utilization of α-KG by myocardial mitochondria of CRF rats is due to reduced V(max) of α-KGDH and that both derangements are mediated by excess PTH or a metabolic consequence of the secondary hyperparathyroidism of CRF