Effects of hyperketonemia on mouse embryonic and fetal glucose metabolism in vitro.
The ketone body beta-hydroxybutyrate (B-OHB) has been shown to be teratogenic to early-somite mouse embryos, although the mechanism responsible for these defects has not been determined. In an attempt to define this mechanism, the present study investigated the normal pattern of both glucose and B-OHB utilization in the developing embryo and fetus. Furthermore, the metabolic interaction of these two substrates, i.e., the potential for B-OHB to inhibit glycolysis, was studied. All studies compared early and late embryonic periods of development as well as fetal stages. The results show that the early embryo relies almost exclusively on glycolysis for energy metabolism and suggests that there is an increasing importance of the Krebs cycle with increasing gestational age. Similarly, the early embryo has a low capacity to metabolize B-OHB, whereas later gestational stages display a greater rate of utilization. Finally, there appears to be no inhibition of glycolysis by B-OHB (via so-called "substrate interactions") during early embryonic stages. However, the compound significantly inhibits glycolysis during later embryonic and fetal stages. These studies suggest that the teratogenicity of B-OHB in the early embryo is not due to its effects on modulating glycolysis, although this mechanism may be operating at later periods of gestation.
D020155:3-Hydroxybutyric Acid; D000818:Animals; D002952:Citric Acid Cycle; D004622:Embryo, Mammalian / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006885:Hydroxybutyrates / Q000378:metabolism / Q000633:toxicity*; D007657:Ketone Bodies / Q000633:toxicity*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D051379:Mice; D011247:Pregnancy
D006885:Hydroxybutyrates; D007657:Ketone Bodies; D007773:Lactates; D019344:Lactic Acid; D005947:Glucose; D020155:3-Hydroxybutyric Acid