QUANTITATION OF THE EFFECT OF L-CARNITINE ON THE LEVELS OF ACID-SOLUBLE SHORT-CHAIN ACYL-COA AND COASH IN RAT-HEART AND LIVER-MITOCHONDRIA

  • 25 January 1988
    • journal article
    • research article
    • Vol. 263  (3) , 1151-1156
Abstract
The steady state levels of mitochondrial acyl-CoAs produced during the oxidation of pyruvate .alpha.-ketoisovalerate, .alpha.-ketoisocaproate, and octanoate during state 3 and 4 respiration by rat heart and liver mitochondria were determined. Addition of carnitine lowered the amounts of individual short-chain acyl-CoAs and increased CoASH in a manner that was both tissue- and substrate-dependent. The largest effects were on acetyl-CoA derived from pyruvate in heart mitochondria using either state 3 or state 4 oxidative conditions. Carnitine greatly reduced the amounts of propionyl-CoA derived from .alpha.-ketoisovalerate, while smaller effects were obtained on the branched-chain acyl-CoA levels, consistent with the latter acyl moieties being poorer substrates for carnitine acetyltransferase and also poorer substrates for the carinitine/acylcarnitine translocase. The levels of acetyl-CoA in heart and liver mitochondria oxidizing octanoate during state 3 respiration were lower than those obtained with pyruvate. The rate of acetylcarnitine efflux from heart mitochondria during state 3 (with pyruvate or octanoate as substrate, in the presence or absence of malate with 0.2 mM carnitine) shows a linear response to the acetyl-CoA/CoASH ratio generated in the absence of carnitine. This relationship is different for liver mitochondria. These data demonstrate that carnitine can modulate the aliphatic short-chain acyl-CoA/CoA ratio in heart and liver mitochondria and indicate that the degree of modulation varies with the aliphatic acyl moiety.