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

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.