Development of Enzymes of Glycolysis and Gluconeogenesis in Human Fetal Liver

Abstract

The activities of two key enzymes of glycolysis and two key enzymes of gluconeogenesis were measured in liver samples from 44 human fetuses ranging in gestational age from 20 weeks to term, from infants to 10 years and from adults from 21 to 58 years. Specific activities of both gluconeogenic enzymes, fructose1,6-biphosphatase and phosphoenolpyruvate carboxykinase, increased throughout the period of fetal development examined, and rose to near adult levels after birth. The activities of both glycolytic enzymes, phosphofructokinase 1 and pyruvate kinase, were lower in fetal than in pediatric and adult samples. For both of these enzymes, there was a significant reduction in activity of livers from fetuses of 34–37 weeks’ gestation. Both enzymes showed hyperbolic kinetics at 24 weeks’ gestation, but this changed to sigmoid kinetics during the 34-37 weeks’ period of low activity. The data indicate that during the last weeks of gestation, inhibition of the activities of these two glycolytic enzymes, coupled with the rise in the two gluconeogenic enzymes, may reflect a change in liver from a primarily glycolytic role in the first two trimesters to a gluconeogenic role shortly before birth.

A Screen Using iPSC-Derived Hepatocytes Reveals NAD+ as a Potential Treatment for mtDNA Depletion Syndrome

“…We first examined the mRNA levels from 15 genes that were defined by the Gene Ontology Consortium ( http://www.geneontology.org ) as encoding proteins with roles in glycolysis and 67 genes that encoded proteins involved in electron transport chain and mitochondrial respiration ( Figure 1A ). As expected, expression of electron transport chain genes was low in human fetal livers (20–38 weeks of gestation), which rely on glycolysis for ATP production, but high in adult livers that primarily use mitochondrial respiration ( Sadava et al, 1992 ). Both iPSCs and cells at early stages of differentiation primarily expressed glycolytic genes.…”

Modulation of glycolysis induction in primary cultures of rabbit kidney proximal tubule cells: the role of shaking, glucose and insulin.

“…These results suggest, as has already been pointed out by Tang et aI., (1989) possible loss of the feed back regulation of the glycolysis pathway by intracellular ATP levels in cultured cells. Sadawa et al (1992) report the occurence of several isoforrns with variation in their kinetic properties for phosphofructokinase and pyruvate kinase with higher KIn values, sigmoid Cell Biology International, Vol. 17, No.…”

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

“…Similar to sheep and humans (Sadava et al . ; Houin et al . ), fetal gluconeogenesis does not take place until late gestation (Jones & Ashton, ), meaning the fetus is dependent on glucose delivery from the mother down a concentration gradient.…”