Inhibition by fatty acyl esters of adenine nucleotide translocation in rat‐liver mitochondria

The Adenine Nucleotide Translocase: A Central Component of the Mitochondrial Permeability Transition Pore and Key Player in Cell Death

“…Since the UCPs are close relatives of ANT it would seem quite likely that a ubiquinone binding site might also exist on the ANT. Fatty acids, and more especially fatty acyl CoA esters, are also potent ligands of the ANT that induce the "c" conformation, inhibit transport activity and, in the former case, induce proton translocating activity by the ANT [37,[118][119][120]. This offers a potential explanation as to why fatty acids, and especially long chain unsaturated ones such as arachidonic acid and retinoic acid stimulate MPTP opening and enhance cell death [120][121][122][123].…”

Ketogenesis in rat‐liver mitochondria: Stimulation by palmityl‐coenzyme A

“…351, and the intracellular distribution of long-chain acyl-CoA to be homogeneous, one arrives at a long-chain acyl-CoA concentration of 0.8 nmole per mg protein. This value exceeds the Ki of the AdN translocator for palmityl-CoA with respect to ADP (0.5 nmole/mg protein) calculated for isolated mitochondria in our preceding paper [6]. It should be noted, however, that differences in the binding affinities of the various proteins, competition of fatty acids and fatty acyl-esters for the same binding sites as well as compartmentation may introduce errors in the above calculation.…”

“…Mitochondrial protein, 9.2 mg. The effect of added CoASH was already discussed earlier [6] : In ATPase experiments it was observed that in the presence of Mg2+; ATP, palmitate and CoASH the"external" palmityl-CoA synthetase [23] builds up inhibitory levels of extramitochondrial palmityl-CoA, provided carnitine is absent. Obviously, this external activation can proceed equally well in oxidation experiments in the presence of hexokinase [cf.…”

“…Bovine serum albumin (BSA), fraction V, was defatted and dialyzed before use [ 161. Hexokinase was also dialyzed and its activity (U) after dialysis was measured as glucose-6-phosphate production @moles/min) at 25" in the above-mentioned standard medium, ADP being re-117 placed by 5 mM ATP. Other biochemicals and experimental details were as previously described [6].…”

Effect of I-Carnitine Chloride and Its Acetyl Derivative on the Electrophysiological Derangement Induced by Palmityl-I-Carnitine in Isolated Canine Ventricular Muscle

“…As the reason of electrophysiological derangements induced by palmityl-l-carnitine, an accumulation of acyl CoA may be invoked, the accumulation of which was shown to produce an inhibition of the adenine nucleotide translocase and a depletion of the cytoplasmic ATP. The reduction of APD produced by palmitate was ascribed to a depletion of the cytoplasmic ATP (17 Indeed, the inhibition of the adenine nucleotide translocase of liver mitochondria (20) by long chain acylcarni tine have been reported. However, with heart mitochondria, Pande and Blanchaer (7) failed to show such an effect with palmi tylcarnitine.…”