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 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.
D000818:Animals; D004622:Embryo, Mammalian; D004798:Enzymes / Q000502:physiology*; D005260:Female; D005492:Folic Acid / Q000009:adverse effects / Q000032:analysis; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000009:adverse effects; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D014817:Vitelline Membrane / Q000166:cytology / Q000187:drug effects
D004798:Enzymes; D007527:Isoenzymes; D005492:Folic Acid; D007770:L-Lactate Dehydrogenase