Pennington S N, Taylor W A
Prostaglandins. 1983 Feb;25(2):291-7. doi: 10.1016/0090-6980(83)90111-9.
Several lines of investigation have suggested that exposure to ethanol may lead to alterations in both the synthesis and degradation of the E and F series of prostaglandins (PG). It has been suggested that these changes in PG metabolism underlie certain of the pathophysiological consequences of chronic alcoholism but few data are available as to the mechanism responsible for these changes. We now report that chronic exposure to ethanol in moderate doses (17% total dietary calories as ethanol) and high doses (35% total dietary calories as ethanol) results in a concentration dependent loss of renal 15-hydroxy-prostaglandin dehydrogenase for the NAD mediated reactions. Soluble fractions of kidney homogenates in the presence of greater than 10 Km concentrations of NAD exhibited dose dependent loss of specific and total organ PG dehydrogenase activity toward PGE2 and F2 alpha. A similar dose dependent decrease in the Vmax of the NAD mediated reaction was measured for the oxidation of PGE1, E2, and F2 alpha. Moderate doses of ethanol resulted in an increase in the Km for PGE2 and F2 alpha. Km values for the NADP mediated reactions were not significantly influenced by exposure to high doses of ethanol other than for PGE1. These data suggest that chronic ethanol consumption results in a dose dependent, selective inhibition of the metabolism of PGs of the "2" series by the renal PGDH enzyme which utilizes NAD.
多项研究表明，接触乙醇可能会导致前列腺素（PG）E系列和F系列的合成与降解发生改变。有人提出，PG代谢的这些变化是慢性酒精中毒某些病理生理后果的基础，但关于导致这些变化的机制的数据却很少。我们现在报告，长期中等剂量（占总膳食热量的17%为乙醇）和高剂量（占总膳食热量的35%为乙醇）接触乙醇会导致肾脏中参与NAD介导反应的15-羟基前列腺素脱氢酶浓度依赖性丧失。在NAD浓度大于10Km的情况下，肾脏匀浆的可溶部分对PGE2和F2α表现出特异性和总器官PG脱氢酶活性的剂量依赖性丧失。对于PGE1、E2和F2α的氧化，也测量到了NAD介导反应的Vmax有类似的剂量依赖性降低。中等剂量的乙醇导致PGE2和F2α的Km增加。除了PGE1外，高剂量乙醇暴露对NADP介导反应的Km值没有显著影响。这些数据表明，长期摄入乙醇会导致肾脏中利用NAD的PGDH酶对“2”系列PG的代谢产生剂量依赖性、选择性抑制。
