Department of Veterinary Medicine, Institute of Veterinary Physiology, Free University of Berlin, Berlin, Germany.
IUBMB Life. 2010 Dec;62(12):869-77. doi: 10.1002/iub.400.
Gluconeogenesis is a crucial process to support glucose homeostasis when nutritional supply with glucose is insufficient. Because ingested carbohydrates are efficiently fermented to short-chain fatty acids in the rumen, ruminants are required to meet the largest part of their glucose demand by de novo genesis after weaning. The qualitative difference to nonruminant species is that propionate originating from ruminal metabolism is the major substrate for gluconeogenesis. Disposal of propionate into gluconeogenesis via propionyl-CoA carboxylase, methylmalonyl-CoA mutase, and the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK) has a high metabolic priority and continues even if glucose is exogenously supplied. Gluconeogenesis is regulated at the transcriptional and several posttranscriptional levels and is under hormonal control (primarily insulin, glucagon, and growth hormone). Transcriptional regulation is relevant for regulating precursor entry into gluconeogenesis (propionate, alanine and other amino acids, lactate, and glycerol). Promoters of the bovine pyruvate carboxylase (PC) and PEPCK genes are directly controlled by metabolic products. The final steps decisive for glucose release (fructose 1,6-bisphosphatase and glucose 6-phosphatase) appear to be highly dependent on posttranscriptional regulation according to actual glucose status. Glucogenic precursor entry, together with hepatic glycogen dynamics, is mostly sufficient to meet the needs for hepatic glucose output except in high-producing dairy cows during the transition from the dry period to peak lactation. Lactating cows adapt to the increased glucose requirement for lactose production by mobilization of endogenous glucogenic substrates and increased hepatic PC expression. If these adaptations fail, lipid metabolism may be altered leading to fatty liver and ketosis. Increasing feed intake and provision of glucogenic precursors from the diet are important to ameliorate these disturbances. An improved understanding of the complex mechanisms underlying gluconeogenesis may further improve our options to enhance the postpartum health status of dairy cows.
糖异生是在葡萄糖供应不足时维持血糖稳态的关键过程。由于摄入的碳水化合物在瘤胃中被有效地发酵为短链脂肪酸，反刍动物在断奶后需要通过从头合成来满足大部分葡萄糖需求。与非反刍动物物种的定性差异在于，来自瘤胃代谢的丙酸是糖异生的主要底物。通过丙酰辅酶 A 羧化酶、甲基丙二酰辅酶 A 变位酶和胞质磷酸烯醇丙酮酸羧激酶（PEPCK）将丙酸转化为糖异生，具有较高的代谢优先级，即使葡萄糖外源性供应，这种转化也会继续进行。糖异生在转录和几个转录后水平受到调节，并受激素控制（主要是胰岛素、胰高血糖素和生长激素）。转录调节与调节前体进入糖异生（丙酸、丙氨酸和其他氨基酸、乳酸盐和甘油）有关。牛丙酮酸羧化酶（PC）和 PEPCK 基因的启动子直接受代谢产物的控制。决定葡萄糖释放的最后步骤（果糖 1,6-二磷酸酶和葡萄糖 6-磷酸酶）似乎高度依赖于根据实际葡萄糖状态的转录后调节。除了在从干奶期过渡到产奶高峰期的高产奶牛中，糖异生前体的进入与肝糖原动态一起，对于满足肝葡萄糖输出的需求来说通常是足够的。泌乳奶牛通过动员内源性糖异生底物和增加肝 PC 表达来适应乳糖生产对葡萄糖需求的增加。如果这些适应失败，脂质代谢可能会发生改变，导致脂肪肝和酮病。增加饲料摄入量和提供饮食中的糖异生前体对于改善这些紊乱非常重要。对糖异生背后复杂机制的深入了解可能会进一步提高我们增强奶牛产后健康状况的选择。
