The metabolism of 4-pentenoic acid, a hypoglycemic agent and inhibitor of fatty acid oxidation, has been studied in rat heart mitochondria. Confirmed was the conversion of 4-pentenoic acid to 2,4-pentadienoyl coenzyme A (CoA), which either is directly degraded via beta-oxidation or is first reduced in a NADPH-dependent reaction before it is further degraded by beta-oxidation. At pH 6.9, the NADPH-dependent reduction of 2,4-pentadienoyl-CoA proceeds 10 times faster than its degradation by beta-oxidation. At pH 7.8, this ratio is only 2 to 1. The direct beta-oxidation of 2,4-pentadienoyl-CoA leads to the formation of 3-keto-4-pentenoyl-CoA, which is highly reactive and spontaneously converts to another 3-ketoacyl-CoA derivative (compound X). 3-Keto-4-pentenoyl-CoA is a poor substrate of 3-ketoacyl-CoA thiolase (EC 2.3..1.16) whereas compound X is not measurably acted upon by this enzyme. The effects of several metabolites of 4-pentenoic acid on the activity of 3-ketoacyl-CoA thiolase were studied. 3,4-Pentadienoyl-CoA is a weak inhibitor of this enzyme that is protected against the inhibition by acetoacetyl-CoA. The most effective inhibitor of 3-ketoacyl-CoA thiolase was found to be 3-keto-4-pentenoyl-CoA, which inhibits the enzyme in both a reversible and irreversible manner. The reversible inhibition is possibly a consequence of the inhibitor being a poor substrate of 3-ketoacyl-CoA thiolase. It is concluded that 4-pentenoic acid is metabolized in mitochondria by two pathways. The minor yields 3-keto-4-pentenoyl-CoA, which acts both as a reversible and as a irreversible inhibitor of 3-ketoacyl-CoA thiolase and consequently of fatty acid oxidation.

中文翻译：

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4-戊烯酸的代谢和4-戊烯酸代谢产物对硫解酶的抑制。

已经在大鼠心脏线粒体中研究了降糖药和脂肪酸氧化抑制剂4-戊烯酸的代谢。证实了4-戊烯酸向2,4-戊二烯酰辅酶A（CoA）的转化，该酶要么通过β-氧化直接降解，要么先在NADPH依赖性反应中还原，然后再通过β-氧化降解。在pH 6.9时，依赖于NADPH的2,4-戊二烯酰辅酶A的还原过程比其通过β氧化降解的过程快10倍。在pH 7.8时，该比例仅为2：1。2，4-戊二烯酰-CoA的直接β-氧化导致形成3-酮基-4-戊烯二酰-CoA，其具有高反应性并自发转化为另外3 -酮酰基-CoA衍生物（化合物X）。3-Keto-4-pentenoyl-CoA是3-ketoacyl-CoA巯基酶的弱底物（EC 2.3.1。16），而化合物X不能被这种酶作用。研究了4-戊烯酸的几种代谢产物对3-酮酰基-CoA硫解酶活性的影响。3,4-戊二烯酰基-CoA是该酶的弱抑制剂，具有抗乙酰乙酰基-CoA抑制作用。发现3-酮基-CoA硫解酶的最有效抑制剂是3-酮-4-戊烯基-CoA，其以可逆和不可逆的方式抑制该酶。可逆的抑制作用可能是由于该抑制剂是3-酮酰基-CoA硫解酶的较弱底物所致。结论是4-戊烯酸在线粒体中通过两种途径代谢。少量生成3-酮-4-戊烯酰-CoA，它既是可逆的又是不可逆的3-酮酰基-CoA硫解酶的抑制剂，因此是脂肪酸氧化的抑制剂。