Carnitine palmitoyltransferase I. Inhibition by D-galactosamine and role of phospholipids.

Palmitate oxidation by liver mitochondria from rats treated with D-galactosamine (GalN) was markedly inhibited, 3 h after administration. The mitochondrial defect responsible for this inhibition was shown to be an inhibition of the activity of palmitoylcarnitine transferase I (EC 2.3.1.21). Apparent Km of the enzyme remained unchanged whereas apparent V was reduced by 30%. Addition of 10 mM GalN did not impair the activity of palmitoylcarnitine transferase I in mitochondria isolated from normal rats. Inhibition of palmitoylcarnitine biosynthesis by GalN treatment was completely reversed by phospholipid supply. At this stage of intoxication, mitochondrial phospholipid content was decreased whereas incorporation of [14C]palmitate into phospholipids in isolated hepatocytes was drastically inhibited: the phosphatidylcholine/phosphatidylethanolamine ratio was reduced by 33%. The results obtained from these studies show that the depletion of the phospholipid membrane content could account for the altered functional activity of palmitoylcarnitine transferase I.