Alterations in carnitine-acylcarnitine translocase activity and in phospholipid composition in heart mitochondria from hypothyroid rats.
Changes in mitochondrial fatty acid metabolism may underlie the decline in cardiac function in the hypothyroid animals. The effect of hypothyroidism on fatty acid oxidation, carnitine-acylcarnitine translocase activity and lipid composition in rat heart mitochondria has been examined. Rates of mitochondrial fatty acid oxidation as well as carnitine-carnitine and carnitine-palmitoylcarnitine exchange reactions were all depressed in heart mitochondria isolated from hypothyroid rats. Kinetic analysis of the carnitine-carnitine exchange reaction showed that the hypothyroid state affects the Vmax of this process, while having no effect on the K(m) value. Heart mitochondrial inner membrane lipid composition was significantly altered in hypothyroid rats. Cardiolipin, particularly, was found to decrease (by around 36%). Alterations in fatty acid pattern of mitochondrial inner membrane preparations from hypothyroid rats were also found. The effects of the hypothyroid state on fatty acids oxidation, carnitine translocase activity and phospholipid composition were completely reversed by following treatment of hypothyroid rats with thyroid hormone. A lower cardiolipin content in the mitochondrial inner membrane offers a plausible mechanism to explain the decline in the translocase activity in hypothyroidism.
Paradies
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Department of Biochemistry and Molecular Biology, University of Bari, Italy.
Ruggiero
F M
FM
Petrosillo
G
G
Quagliariello
E
E
D000818:Animals; D002308:Cardiolipins / Q000378:metabolism; D002333:Carnitine Acyltransferases / Q000378:metabolism*; D002474:Cell-Free System; D005227:Fatty Acids / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism*; D007700:Kinetics; D008929:Mitochondria, Heart / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000494:pharmacology
D002308:Cardiolipins; D005227:Fatty Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D014284:Triiodothyronine; D002333:Carnitine Acyltransferases