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.
The steady state levels of mitochondrial acyl-CoAs produced during the oxidation of pyruvate, alpha-ketoisovalerate, alpha-ketoisocaproate, and octanoate during state 3 and state 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 carnitine/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.
Lysiak
W
W
Department of Biochemistry, Michigan State University, East Lansing 48824.
Lilly
K
K
DiLisa
F
F
Toth
P P
PP
Bieber
L L
LL
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D002331:Carnitine / Q000494:pharmacology*; D003065:Coenzyme A / Q000378:metabolism*; D045782:Hemiterpenes; D007651:Keto Acids / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; D002210:Caprylates; D045782:Hemiterpenes; D007651:Keto Acids; D011773:Pyruvates; C001505:alpha-ketoisovalerate; C013082:alpha-ketoisocaproic acid; D019289:Pyruvic Acid; C031492:octanoic acid; D002331:Carnitine; D003065:Coenzyme A