No abstract

Hz). l,4,6-Triphenylpyridinium-2-carboxylate (11). 2-(Ethoxycarbonyl)-1,4,6-triphenylpyridinium tetrailuoroborate (8a; 5 g, 10.7 mmol) was stirred at 25 °C as a suspension in aqueous NaOH (0.5 N, 25 mL, 12.5 mmol) for 24 h. The white solid was filtered off and washed with water (500 mL) and ether (50 mL) to give the betaine as microcrystals: 3.2 g (85%); mp 150 °C dec (satisfactory analysis not obtained due to decomposition on attempted recrystallization); IR (CHBr3) 1650 (s), 1618 (s) cm"1; NMR (CDC13/TFA) 7.S-7.9 (m, 15 ), 8.10 (d, 1 H, J = 2 Hz), 8.38 (d, 1 H, J = 2 Hz).1,2,4-Triphenylpyridinium iodide (13) was obtained by refluxing 1,4,6-triphenylpyridinium-2-carboxylate (11) (2 g, 5.7 mmol) with aqueous HI (65%, 1.20 g, 6.1 mmol) in THF (50 mL)for 4 h to yield yellow crystals (washed with ether). Recrystallization from absolute EtOH gave yellow needles: 2.1 g (85%); mp 273-274 °C; IR (CHBr3) 1630 cm"1; NMR (CDC13/TFA) 7.6-7.9 (m, 15 ), 8.

In order to understand the role of carnitine metabolites in the genesis of cellular dysfunction and damage due to myocardial ischemia, the effects of 1-100 microM L-carnitine, acetylcarnitine, propionylcarnitine, and palmitoylcarnitine were investigated on rat heart sarcolemmal, sarcoplasmic reticular, and mitochondrial ATPase activities. Palmitoylcarnitine, unlike acetylcarnitine, propionylcarnitine and carnitine, produced marked inhibitory actions on sarcolemmal Na,K-ATPase and Ca2(+)-stimulated ATPase, as well as sarcoplasmic reticular Ca2(+)-stimulated ATPase activities; Na,K-ATPase was most sensitive. Although palmitoylcarnitine, unlike carnitine or its short-chain fatty-acid derivatives, also depressed sarcolemmal Ca2+ ATPase or Mg2+ ATPase, sarcoplasmic reticular Mg2+ ATPase, and mitochondrial Mg2+ ATPase, mitochondria were less sensitive in comparison to other organelles. Myofibrillar Ca2(+)-stimulated ATPase was slightly inhibited by very high concentrations of palmitoylcarnitine only. It is suggested that the observed depression of the sarcolemmal Na(+)-pump system by low concentrations of long-chain acyl derivatives of carnitine may contribute towards the pathogenesis of arrhythmias due to myocardial ischemia. Furthermore, the inhibition of Ca2(+)-pump mechanisms in the sarcolemmal and sarcoplasmic reticular membranes by relatively high concentrations of palmitoylcarnitine may result in the occurrence of intracellular Ca2+ overload and subsequent cell damage, as well as cardiac dysfunction due to myocardial ischemia.

To evaluate changes in heart sarcolemmal phosphatidylethanolamine (PE) N-methylation, left ventricular hypertrophy was induced in rabbits by banding the abdominal aorta for 4, 8, 14, and 22 wk. The degree of cardiac hypertrophy did not change over the period of time studied. Three catalytic sites involved in the sequential methyl transfer reactions were examined by assaying the incorporation of radiolabeled methyl groups from S-adenosyl-L-methionine (0.055, 10, and 150 microM) into sarcolemmal PE molecules under optimal conditions. Total N-methylation activity at all three sites was significantly increased at 4 wk, unaltered at 8 and 14 wk, and depressed at 22 wk after banding the aorta. Similar biphasic changes were seen for the individual methylated lipid products (monomethylphosphatidylethanolamine, dimethylphosphatidylethanolamine, and phosphatidylcholine) specifically formed at each catalytic site. At all three sites, alterations in PE N-methylation at 22 wk were associated with changes in Vmax values without any change in the apparent affinity for S-adenosyl-L-methionine. In contrast to sarcolemma, a significant increase of the PE N-methylation activity at sites I and III was observed in the sarcoplasmic reticular (microsomal) fraction from 22-wk hypertrophied hearts; the increase in site II was not significant. On the other hand, no changes in the N-methylation activity of the mitochondrial fraction were seen at 22 wk after banding. These findings indicate the occurrence of biphasic alterations in the sarcolemmal PE N-methylation activity during the presence of a stable degree of hypertrophy.