Fatty acid oxidation in the myocardium: effects of parathyroid hormone and CRF.
Fatty acids constitute an important substrate utilized by the myocardium as a major fuel for energy production; certain data suggest that oxidation of long chain fatty acids (LCFA) may be impaired in uremia, and such a derangement could, in part, contribute to the myocardiopathy of uremia. The latter is associated with secondary hyperparathyroidism and PTH has been shown to affect myocardial metabolism. The present study evaluated in rats the effects of four days administration of PTH and 21 days of chronic renal failure (CRF) with and without excess PTH on oxidation of alpha-ketoglutarate, beta-hydroxybutyric acid, LCFA and short chain fatty acids (SCFA). PTH impaired oxidation of alpha-ketoglutarate, LCFA, SCFA, but not of beta-hydroxybutyric acid and reduced the activity of carnitine palmitoyl transferase (CPT). Inactivation of the PTH abolished its effects. CRF rats with intact parathyroid glands also had impaired oxidation of LCFA and CTP activity. Carnitine contents of myocardium were not altered. The data show that PTH excess in normal rats is associated with impaired oxidation of LCFA and SCFA, and secondary hyperparathyroidism in CRF animals impairs oxidation of LCFA. This effect is due to: 1) reduction in the activity of CPT, a key enzyme for the transport of LCFA to mitochondrial matrix for beta-oxidation; and 2) impairment in beta-oxidation. The data provide for new and additional pathway through which excess PTH and CRF can affect myocardial metabolism.
Smogorzewski
M
M
Division of Nephrology, University of Southern California, School of Medicine, Los Angeles.
Perna
A F
AF
Borum
P R
PR
Massry
S G
SG
D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006962:Hyperparathyroidism, Secondary / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D010281:Parathyroid Hormone; D002334:Carnitine O-Palmitoyltransferase