Horton W E, Sadler T W, Hunter E S
Teratology. 1985 Apr;31(2):227-33. doi: 10.1002/tera.1420310207.
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.
酮体β-羟基丁酸酯（B-OHB）已被证明对早期体节小鼠胚胎具有致畸性，尽管导致这些缺陷的机制尚未确定。为了确定这一机制，本研究调查了发育中的胚胎和胎儿对葡萄糖和B-OHB的正常利用模式。此外，还研究了这两种底物的代谢相互作用，即B-OHB抑制糖酵解的可能性。所有研究都比较了胚胎发育的早期和晚期以及胎儿阶段。结果表明，早期胚胎几乎完全依赖糖酵解进行能量代谢，这表明随着胎龄增加，三羧酸循环的重要性日益增加。同样，早期胚胎代谢B-OHB的能力较低，而妊娠后期的利用率更高。最后，在胚胎早期阶段，B-OHB似乎不会抑制糖酵解（通过所谓的“底物相互作用”）。然而，该化合物在胚胎后期和胎儿阶段会显著抑制糖酵解。这些研究表明，B-OHB在早期胚胎中的致畸性并非源于其对调节糖酵解的影响，尽管这一机制可能在妊娠后期起作用。
