Carnitine palmitoyltransferase I

Abstract

Palmitate oxidation by liver mitochondria from rats treated with D-galactosamine (GalN) was markedly 1. The mitochondrial defect responsible for this inhibition was shown to be an inhibition of the activity of 2. Apparent & of the enzyme remained unchanged whereas apparent V was reduced by 30%.3. Addition of 10 mM GalN did not impair the activity of palmitoylcarnitine transferase I in mitochondria 4. Inhibition of palmitoylcarnitine biosynthesis by GalN treatment was completely reversed by phospholipid 5. At this stage of intoxication, mitochondrial phospholipid content was decreased whereas incorporation of ['4C]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.inhibited, 3 h after administration. palmitoylcarnitine transferase I (EC 2.3.1.21).isolated from normal rats.supply.In a previous study [l] we reported that treatment for 3 h with D-galactosamine (GalN) inhibits I4CO2 production from a long-chain fatty acid by hepatocytes. On the opposite, the 14C02 release from a short-chain fatty acid, namely octanoate, was not decreased. Mitochondria1 respiration rate studies have proved that GalN administration acts on the fatty acid pathway prior to P-oxidation. Thus, the system for transfer of long-chain fatty acids across the mitochondrial membrane seems to be implicated in the observed inhibition. Two pools of long-chain carnitine acyltransferases are involved in this transfer [2-61; one of which is latent (transferase 11) and the other overt (transferase I) in intact mitochondria. Our findings suggest that only the overt form was impaired by GalN treatment; this inhibition was not due to a depletion of carnitine content. The purpose of the present study was to elucidate whether GalN administration alters palmitoyl-Lcarnitine formation by the transferase, in liver mitochondria. The findings here presented provide evidence that GalN administration depressed transferase I activity by modifying mitochondrial membrane. EXPERIMENTAL PROCEDURES AnimalsMale Wistar rats (C.E.R.J., F-53680) weighing 200-240 g were kept at 20-22 "C with a photoperiod of 12 h dark, 12 h light. They were starved overnight before the experiments and given water ad libitum. At 07:30 h D-galactosamine (GalN), Abbreviations. GalN, D-galactosamine; PtdCho, phosphatidylcholine; PtdEtn, phosphatidylethanolamine. neutralized at pH 7.4 was administered (60 mg/100 g body wt) intraperitoneally, control rats receiving an equal volume of saline. Animals are sacrified 3 h after GalN injection. Isolation of hepatocytesFor the preparation of isolated hepatocytes, the animals were anesthesized by intraperitoneal injection of sodium pentobarbital (50 mg/100 g body wt) 3 h after GalN injection and hepatocytes were isolated by collagenase perfusion [7] in a Krebs-Ringer bi...

Amelioration of galactosamine-induced nephrotoxicity by a protein isolated from the leaves of the herb, Cajanus indicus L

“…Mangeney-Andreani et al [10] suggested that energy metabolism of hepatocytes was also inhibited by GalN application. In addition, report from Sire et al [48] reveals that GalN damaged the enzymes involved in the transport of substrates to the mitochondria and consequently modified the phospholipid composition of the membrane. It has been observed that patient suffering with liver disease have a decrease in renal blood flow, indicating renal vasoconstriction and this effect is more prominent in those people affected with HRS [49].…”

Mouse Models of Liver Fibrosis Mimic Human Liver Fibrosis of Different Etiologies

“…d-GalN causes UDP glucose and UDP galactose deficiency, loss of intracellular calcium homeostasis, inhibition of energy metabolism of hepatocytes, and injuries of the mitochondrial enzymes affecting lipoprotein interactions[48–50]. To understand the inflammation induced pathway in hepatocytes, d-GalN/Lipopolysaccharide treatment was performed to show that hepatic injury is facilitated by TNF-α.…”

Regulatory properties of a mutant carnitine palmitoyltransferase in human skeletal muscle

“…The influence of the membranous environment on the enzyme is also shown by the effect of nonionic detergents and acylcarnitine micelles on the kinetic properties of the enzyme [49], the decrease in CPT activity when membrane composition is altered by treatment with D-galactosamine [50], and the dependence of D-palmitoylcarnitine and malonyl-CoA sensitivity on membrane association of the enzyme [32,33,381. The loss of mutant CPT activity after treatment with Triton X-100 suggest an abnormal dependence of the mutant enzyme on its membranous environment.…”