铵对大鼠肝线粒体脂肪酸氧化的抑制作用。雷氏综合征和尿素循环缺陷中脂肪肝的一个可能原因。

Ammonium inhibition of fatty acid oxidation in rat liver mitochondria. A possible cause of fatty liver in Reye's syndrome and urea cycle defects.

作者信息

Maddaiah V T

出版信息

Biochem Biophys Res Commun. 1985 Mar 15;127(2):565-70. doi: 10.1016/s0006-291x(85)80197-2.

Abstract

NH4C1 inhibited oxygen consumption (State 3, ADP induced) by rat liver mitochondria respiring on palmitoyl-L-carnitine or octanoic acid but not on succinate or malate + glutamate. The inhibition became apparent at 0.02 mM reaching a plateau (40%) at 2 mM NH4C1. Similar inhibition was observed with uncoupled (in the presence of 2, 4-dinitrophenol) mitochondria. The inhibition of uncoupled mitochondria was reversible as the rate of respiration with palmitoyl-L-carnitine was further increased by succinate and the total rate was unaffected by NH4C1. Therefore, NH+4 inhibition of mitochondrial respiration may lead to fatty infiltration and be one of the causes of the pathophysiology in children with Reye's syndrome and disorders of urea cycle enzymes.

摘要

氯化铵抑制大鼠肝脏线粒体在以棕榈酰-L-肉碱或辛酸为呼吸底物时的氧消耗（状态3，由ADP诱导），但对以琥珀酸或苹果酸+谷氨酸为呼吸底物时无抑制作用。在0.02 mM时抑制作用开始明显，在2 mM氯化铵时达到平台期（40%）。在解偶联（存在2,4-二硝基苯酚）的线粒体中也观察到类似的抑制作用。解偶联线粒体的抑制作用是可逆的，因为琥珀酸可进一步提高以棕榈酰-L-肉碱为底物时的呼吸速率，且总速率不受氯化铵影响。因此，铵离子对线粒体呼吸的抑制可能导致脂肪浸润，是瑞氏综合征患儿及尿素循环酶紊乱病理生理机制的原因之一。