G. Paradies et al., ALTERATIONS IN CARNITINE-ACYLCARNITINE TRANSLOCASE ACTIVITY AND IN PHOSPHOLIPID-COMPOSITION IN HEART-MITOCHONDRIA FROM HYPOTHYROID RATS, Biochimica et biophysica acta. Molecular basis of disease, 1362(2-3), 1997, pp. 193-200
Changes in mitochondrial fatty acid metabolism may underlie the declin
e in cardiac function in the hypothyroid animals. The effect of hypoth
yroidism on fatty acid oxidation, carnitine-acylcarnitine translocase
activity and lipid composition in rat heart mitochondria has been exam
ined. Rates of mitochondrial fatty acid oxidation as well as carnitine
-carnitine and carnitine-palmitoylcarnitine exchange reactions were al
l depressed in heart mitochondria isolated from hypothyroid rats. Kine
tic analysis of the carnitine-carnitine exchange reaction showed that
the hypothyroid state affects the V-max of this process, while having
no effect on the K-m value. Heart mitochondrial inner membrane lipid c
omposition was significantly altered in hypothyroid rats. Cardiolipin,
particularly, was found to decrease (by around 36%). Alterations in f
atty acid pattern of mitochondrial inner membrane preparations from hy
pothyroid rats were also found. The effects of the hypothyroid state o
n fatty acids oxidation, carnitine translocase activity and phospholip
id composition were completely reversed by following treatment of hypo
thyroid rats with thyroid hormone. A lower cardiolipin content in the
mitochondrial inner membrane offers a plausible mechanism to explain t
he decline in the translocase activity in hypothyroidism. (C) 1997 Els
evier Science B.V.