Smogorzewski M, Perna A F, Borum P R, Massry S G
Division of Nephrology, University of Southern California, School of Medicine, Los Angeles.
Kidney Int. 1988 Dec;34(6):797-803. doi: 10.1038/ki.1988.252.
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.
脂肪酸是心肌利用的一种重要底物，作为能量产生的主要燃料；某些数据表明，尿毒症时长链脂肪酸（LCFA）的氧化可能受损，这种紊乱可能在一定程度上导致尿毒症心肌病。后者与继发性甲状旁腺功能亢进有关，并且已证明甲状旁腺激素（PTH）会影响心肌代谢。本研究评估了在大鼠中给予PTH四天以及慢性肾衰竭（CRF）21天（有无过量PTH）对α-酮戊二酸、β-羟基丁酸、LCFA和短链脂肪酸（SCFA）氧化的影响。PTH损害了α-酮戊二酸、LCFA、SCFA的氧化，但不影响β-羟基丁酸的氧化，并降低了肉碱棕榈酰转移酶（CPT）的活性。PTH失活消除了其作用。甲状旁腺完整的CRF大鼠也存在LCFA氧化受损和CTP活性降低的情况。心肌中的肉碱含量没有改变。数据表明，正常大鼠中PTH过量与LCFA和SCFA氧化受损有关，CRF动物中的继发性甲状旁腺功能亢进损害了LCFA的氧化。这种作用归因于：1）CPT活性降低，CPT是将LCFA转运到线粒体基质进行β氧化的关键酶；2）β氧化受损。这些数据提供了新的额外途径，通过该途径过量的PTH和CRF可以影响心肌代谢。
