Regulation of placental enzymes of the carbohydrate and lipid metabolic pathways.
The activity of enzymes with a regulatory function in the pathways of glycolysis, gluconeogenesis, NADPH generation and fatty acid synthesis was measured in the placenta and liver of rats. Compared with the liver, a high activity of pyruvate kinase was found in the placenta, indicating a high glycolytic potential; a small capacity for gluconeogenesis was also present and a moderate to low activity of enzymes associated with lipogenesis. The activity of all placental enzymes fell from day 15 to 20 of gestation irrespective of the pathway they represented. The pattern of decline continued when the gestation was prolonged up to day 26 by the administration of chorionic gonadotropin. The rates of activity disappearance over 11 days of gestation differed for each enzyme, with half-lives ranging from 2.7 days for NADP-malate dehydrogenase to 7 days for glucose-6-phosphate dehydrogenase. In contrast, the activity of hepatic enzymes either remained unchanged or showed individual adaptation to the advancing pregnancy. The regression in placental metabolic capacity after day 15 of gestation was also evident by the decrease in glucose uptake and its channelling to lactate, CO2, glycerol and fatty acids. In addition, placental ageing was associated with triglyceride accumulation, mainly due to the decrease in free fatty acid oxidation. Treatment of pregnant rats with several hormones, while markedly affecting the hepatic enzyme activities, failed to induce appreciable changes in the corresponding placental enzymes. This was illustrated in the case of triiodothyronine treatment. Similarly, insulin deficiency induced by streptozotocin failed to elicit adaptive changes in placental enzyme activities typical of diabetes like those occurring in the maternal liver; some converse responses in the placenta were attributed to hyperglycaemia. On the other hand, responses in some fetal liver enzymes were suggestive of fetal hyperinsulinaemia. These observations indicate that placental enzymes are not susceptible to endocrine regulation and imply that placental metabolism is largely independent of the physiopathological alterations affecting the maternal organism. The gradual activity decreases with gestation suggest that the enzyme complement of the placenta, once developed, is designed to last through its limited lifespan without continuous replenishment. Within this context, no mechanism seems to operate to ind1ce the adaptive synthesis of individual enzymes, and the age of the placenta appears to be the primary factor determining its enzyme activity and metabolic performance.
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D004798:Enzymes / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D005865:Gestational Age; D005943:Gluconeogenesis; D006019:Glycolysis; D008099:Liver / Q000201:enzymology; D009249:NADP / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D000637:Transaminases / Q000378:metabolism
D004798:Enzymes; D005227:Fatty Acids; D009249:NADP; D010088:Oxidoreductases; D000637:Transaminases; D011770:Pyruvate Kinase; D000103:Acetyl-CoA Carboxylase