Netzloff M L, Rennert O M
Ann Clin Lab Sci. 1977 May-Jun;7(3):216-21.
Alterations in multiple molecular forms of enzymes have been described during normal embryogenesis. Changes in electrophoretic patterns, which differ from the normal isozyme ontogeny, occur in embryos and their yolk-sacs during incipient maldevelopment secondary to teratogen exposure. One such isozyme change, in response to a teratogenic regimen using 9-methyl pteroylglutamic acid (PGA), is persistence of lactate dehydrogenase-5 (LDH-5) beyond its time of normal involution in the rat yolk-sac. Since LDH-5 is an allosteric regulatory enzyme which favors anaerobic metabolism, the cellular respiration of 9-methyl PGA-treated embryos was investigated and found to be depressed. However, no changes were found in the oxidative metabolism of visceral yolk-sacs from similarly treated pregnancies. A possible explanation for the unchanged oxygen consumption is the observed simultaneous quantitative alterations in other LDH-yolk-sac isozymes following 9-methyl PGA treatment. Other potential causes include known changes in isozymes other than LDH, limitation of enzyme function by its substrate or co-factor or the presence of a functionally inert LDH-5 isozyme. Changes in LDH and other isozyme patterns and their associated metabolic alterations may eventually prove useful in predicting chemical teratogenicity.
在正常胚胎发育过程中，已发现多种酶分子形式的改变。在致畸剂暴露导致的初期发育不良期间，胚胎及其卵黄囊中会出现电泳图谱的变化，这些变化不同于正常同工酶的个体发育过程。一种这样的同工酶变化是，在使用9-甲基蝶酰谷氨酸（PGA）的致畸方案处理后，大鼠卵黄囊中乳酸脱氢酶-5（LDH-5）在正常退化时间之后仍持续存在。由于LDH-5是一种有利于无氧代谢的别构调节酶，因此对9-甲基PGA处理的胚胎的细胞呼吸进行了研究，发现其受到抑制。然而，在同样处理的妊娠中，内脏卵黄囊的氧化代谢未发现变化。氧消耗未改变的一个可能解释是，在9-甲基PGA处理后，观察到其他LDH-卵黄囊同工酶同时发生了定量改变。其他潜在原因包括已知的LDH以外的同工酶变化、底物或辅因子对酶功能的限制或存在功能惰性的LDH-5同工酶。LDH和其他同工酶模式的变化及其相关的代谢改变最终可能被证明有助于预测化学致畸性。
