Accumulation of Unsaturated Acylcarnitine Molecular Species During Acute Myocardial Ischemia: Metabolic Compartmentalization of Products of Fatty Acyl Chain Elongation in the Acylcarnitine Pool

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Abstract
Long-chain acylcarnitines accumulate during myocardial ischemia and contribute to membrane dysfunction in ischemic zones. On the basis of the 3-fold selectivity for saturated fatty acid accumulation during myocardial ischemia, it was implicitly assumed that saturated long chain acylcarnitine molecular species predominantly accumulated in ischemic myocardium. By exploiting the analytical power of electrospray ionization mass spectroscopy, we now report that unsaturated acylcarnitines are the predominant molecular species of acylcarnitine which accumulate during myocardial ischemia (rank order: octadecadienoyl carnitine > octadecenoyl carnitine > hexadecanoyl carnitine > octadecanoyl carnitine). The aliphatic chain distribution of myocardial acylcarnitine molecular species identified by electrospray ionization mass spectroscopy was independently substantiated by sequential HPLC purification and capillary gas chromatography. Detailed analysis of the individual molecular species of long-chain acylcarnitine demonstrated that fatty acyl chain elongation was prominent in ischemic myocardium (e.g., following 20 min of ischemia, greater than 15% of the accumulated acylcarnitines consisted of 20-carbon unsaturated molecular species). Chain-elongated lipids were essentially confined to the long chain acylcarnitine pool since [9,10-3H]octadec-9‘-enoic acid was converted to [3H]eicosenoyl carnitine (12% of the radiolabeled acylcarnitine pool) in ischemic hearts without substantive amounts of [3H]eicosenoyl residues in the fatty acid, triglyceride, and phospholipid pools. Collectively, these results demonstrate the preponderance of unsaturated acylcarnitines in ischemic myocardium and document the metabolic compartmentation of downstream products of fatty acyl chain elongation in the acylcarnitine pool during ischemia.