Hiltunen J K
Biochem J. 1978 Feb 15;170(2):241-7. doi: 10.1042/bj1700241.
The metabolic effects of the hypoglycaemic agent pent-4-enoate were studied in isolated, beating or potassium-arrested rat hearts. The addition of 0.8mM-pent-4-enoate to the perfusion fluid increased O2 consumption by 76% in the arrested heart and by 14% in the beating heart; the concentration ratio of phosphocreatine/creatine increase concomitantly by 47% and 27% respectively. Perfusion of the heart with pent-4-enoate resulted in a 30-fold increase in the concentration of the pool of tricarboxylic acid-cycle intermediates in the tissue, about 90% of this increase being due to malate. The sum of the concentrations of the myocardial free amino acids remained virtually unchanged during the accumulation of the tricarboxylic acid-cycle intermediates. It was concluded that pent-4-enoate can be effectively metabolized in the myocardium and that its metabolism probably proceeds via propionyl-CoA, since pent-4-enoate reproduces many of the metabolic characteristics of propionate in the cardiac muscle. The accumulation of the tricarboxylic acid-cycle intermediates is probably due to carboxylation of propionyl-CoA. The response pattern of the metabolite concentrations in the cardiac muscle is quite different from that in the liver, in which decrease of the concentrations of the tricarboxylic acid-cycle intermediates has been observed previously [Williamson, Rostand & Peterson (1970) J. Biol. Chem. 245, 3242-3251].
在离体的、跳动的或钾离子停搏的大鼠心脏中研究了降糖药戊-4-烯酸的代谢作用。向灌注液中添加0.8mM戊-4-烯酸，使停搏心脏的耗氧量增加76%，跳动心脏的耗氧量增加14%；磷酸肌酸/肌酸的浓度比分别相应增加47%和27%。用戊-4-烯酸灌注心脏导致组织中三羧酸循环中间产物池的浓度增加30倍，这种增加约90%是由于苹果酸。在三羧酸循环中间产物积累过程中，心肌游离氨基酸浓度的总和基本保持不变。得出的结论是，戊-4-烯酸可在心肌中有效代谢，其代谢可能通过丙酰辅酶A进行，因为戊-4-烯酸重现了丙酸在心肌中的许多代谢特征。三羧酸循环中间产物的积累可能是由于丙酰辅酶A的羧化作用。心肌中代谢物浓度的反应模式与肝脏中的截然不同，在肝脏中先前已观察到三羧酸循环中间产物浓度的降低[威廉姆森、罗斯坦德和彼得森（1970年）《生物化学杂志》245，3242 - 3251]。
