STATKING Clinical Services, Fairfield, OH, USA.
Department of Animal Science, North Carolina State University, Raleigh, NC, USA.
J Nutr. 2020 Sep 1;150(9):2239-2241. doi: 10.1093/jn/nxaa166.
A gluconeogenic precursor is a biochemical compound acted on by a gluconeogenic pathway enabling the net synthesis of glucose. Recognized gluconeogenic precursors in fasting placental mammals include glycerol, lactate/pyruvate, certain amino acids, and odd-chain length fatty acids. Each of these precursors is capable of contributing net amounts of carbon to glucose synthesis via the tricarboxylic acid cycle (TCA cycle) because they are anaplerotic, that is, they are able to increase the pools of TCA cycle intermediates by the contribution of more carbon than is lost via carbon dioxide. The net synthesis of glucose from even-chain length fatty acids (ECFAs) in fasting placental mammals, via the TCA cycle alone, is not possible because equal amounts of carbon are lost via carbon dioxide as is contributed from fatty acid oxidation via acetyl-CoA. Therefore, ECFAs do not meet the criteria to be recognized as a gluconeogenic precursor via the TCA cycle alone. ECFAs are gluconeogenic precursors in organisms with a functioning glyoxylate cycle, which enables the net contribution of carbon to the intermediates of the TCA cycle from ECFAs and the net synthesis of glucose. The net conversion of ECFAs to glucose in fasting placental mammals via C3 metabolism of acetone may be a competent though inefficient metabolic path by which ECFA could be considered a gluconeogenic precursor. Defining a substrate as a gluconeogenic precursor requires careful articulation of the definition, organism, and physiologic conditions under consideration.
糖异生前体是一种生化化合物，通过糖异生途径作用，能够净合成葡萄糖。禁食胎盘哺乳动物中公认的糖异生前体包括甘油、乳酸/丙酮酸、某些氨基酸和奇数链长脂肪酸。这些前体中的每一种都能够通过三羧酸循环（TCA 循环）为葡萄糖合成贡献净碳量，因为它们是补料作用的，也就是说，它们能够通过贡献比通过二氧化碳损失更多的碳来增加 TCA 循环中间产物的池。在禁食胎盘哺乳动物中，仅通过 TCA 循环从偶数链长脂肪酸（ECFAs）净合成葡萄糖是不可能的，因为通过二氧化碳损失的碳量与通过乙酰辅酶 A 从脂肪酸氧化贡献的碳量相等。因此，ECFAs 不符合仅通过 TCA 循环被认为是糖异生前体的标准。在具有功能乙醛酸循环的生物体中，ECFAs 是糖异生前体，能够使碳从 ECFAs 净贡献到 TCA 循环的中间产物，并净合成葡萄糖。在禁食胎盘哺乳动物中，通过丙酮的 C3 代谢将 ECFAs 净转化为葡萄糖可能是一种有效的代谢途径，尽管效率不高，但可以认为 ECFA 是糖异生前体。将底物定义为糖异生前体需要仔细阐明定义、生物体和所考虑的生理条件。
