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.

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

PERNA, Alessandra;
1991

Abstract

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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11591/199156
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact