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Carnitine and carnitine acetyltransferase; their role in development

University of British Columbia

Carnitine (γ-trimethylamino-3-hydroxybutyrate) , a betaine derivative which is widely distributed in mammalian tissues, serves to facilitate the passage of activated fatty acids into mitochondria. The carnitine acyltransferases (acetyl-, octanoyl-, palmityl- and possibly others) esterify tissue acyl-CoA to carnitine producing acylcarnitine which readily passes into mitochondria. Once inside, the fatty acids undergo β-oxidation. The purpose of this study was threefold: to examine changes that occur in blood levels of free, acyl- and total carnitine with starvation and diets varying in lipid content; to compare and contrast changes in blood levels of carnitine during the perinatal period in sheep, rat, rabbit, guinea pig and man; and to measure the activity of carnitine acetyltransferase in mitochondria and microsomes isolated from liver and brown adipose tissue taken during the perinatal period from rat, rabbit and guinea pig. Methods for determining serum levels of free, acyl- and total carnitine were developed and used. Short-term starvation, in man and rat, resulted in a significant decrease in serum levels of free carnitine and a significant increase in acylcarnitine. Free carnitine levels correlated negatively with serum concentrations of D-β-hydroxybutyrate and free fatty acids. In man, the renal clearance of free carnitine decreased while the clearance of acylcarnitine increased. In the rat, total serum carnitine decreased significantly within 24 hours of starvation. By 48 hours, it had increased significantly. A similar decrease in total serum carnitine occurred with a long-chain triglyceride diet. Although total carnitine remained unchanged with a medium-chain triglyceride diet, acylcarnitine levels were twice, and β-D-hydroxybutyrate levels six times, higher than with the long-chain triglyceride diet. In late gestation, total serum carnitine levels in the maternal sheep and rat were significantly higher than in the fetus. There was no difference between maternal and fetal values in the guinea pig and rabbit. At day one, total carnitine had increased significantly in all species except the rabbit. Liver and brown adipose tissue mitochondrial activity of carnitine acetyltransferase was very high in the fetal rabbit and guinea pig and very low in the rat. Activity in the rat increased neonatally reaching a peak at day one in the case of liver and at day 10 in the case of brown fat. Fetal rabbit and guinea pig levels of activity remained unchanged at day one. In rat, liver microsomal carnitine acetyltransferase activity remained at low fetal values until weaning at which time the activity began to increase reaching adult levels by day 30. The data obtained in this study indicate that the oxidation of fatty acids is reflected in serum levels of free and acylcarnitine and in liver mitochondrial carnitine acetyltransferase activity.

Text

2010-03-29

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http://hdl.handle.net/2429/22965

Physiology

University of British Columbia

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