Enzyme Polymorphism and Function During Embryonic Development*

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 dehydrogen ase-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 metabo lism, the cellular respiration of 9-methyl PGA-treated embryos was investi gated 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 treat ment. 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 even tually prove useful in predicting chemical teratogenicity