For dairy production systems, nitrogen is an expensive nutrient and potentially harmful waste product. With three quarters of fed nitrogen ending up in the manure, significant research efforts have focused on understanding and mitigating lactating dairy cows’ nitrogen losses. Recent changes proposed to the Nutrient Requirement System for Dairy Cattle in the US include variable efficiencies of absorbed essential AA for milk protein production. This first separation from a purely substrate-based system, standing on the old limiting AA theory, recognizes the ability of the cow to alter the metabolism of AA. In this review we summarize a compelling amount of evidence suggesting that AA requirements for milk protein synthesis are based on a demand-driven system. Milk protein synthesis is governed at mammary level by a set of transduction pathways, including the mechanistic target of rapamycin complex 1 (mTORC1), the integrated stress response (ISR), and the unfolded protein response (UPR). In tight coordination, these pathways not only control the rate of milk protein synthesis, setting the demand for AA, but also manipulate cellular AA transport and even blood flow to the mammary glands, securing the supply of those needed nutrients. These transduction pathways, specifically mTORC1, sense specific AA, as well as other physiological signals, including insulin, the canonical indicator of energy status. Insulin plays a key role on mTORC1 signaling, controlling its activation, once AA have determined mTORC1 localization to the lysosomal membrane. Based on this molecular model, AA and insulin signals need to be tightly coordinated to maximize milk protein synthesis rate. The evidence in lactating dairy cows supports this model, in which insulin and glucogenic energy potentiate the effect of AA on milk protein synthesis. Incorporating the effect of specific signaling AA and the differential role of energy sources on utilization of absorbed AA for milk protein synthesis seems like the evident following step in nutrient requirement systems to further improve N efficiency in lactating dairy cow rations.

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氨基酸市场：了解基质的供需，以更有效地合成牛奶蛋白质

对于乳制品生产系统，氮是一种昂贵的营养物质，并且可能是有害的废物。随着四分之三的饲喂氮最终进入粪肥，大量的研究工作集中在理解和减轻泌乳奶牛的氮损失上。在美国，对奶牛的营养需求系统提出的最新更改包括吸收牛奶蛋白生产中必需氨基酸的可变效率。站在古老的限制性氨基酸理论的基础上，首次从纯底物系统中分离出来，这可以认识到母牛改变氨基酸代谢的能力。在这篇综述中，我们总结了令人信服的大量证据，这些证据表明AA对牛奶蛋白质合成的要求是基于需求驱动的系统。乳蛋白的合成在乳腺水平上受到一系列转导途径的控制，包括雷帕霉素复合物1（mTORC1）的机制靶标，整合应激反应（ISR）和未折叠蛋白反应（UPR）。在紧密协调下，这些途径不仅控制乳蛋白合成的速度，确定了对氨基酸的需求，而且还操纵着细胞氨基酸的运输，甚至流向乳腺的血液，从而确保了所需营养的供应。这些转导途径，特别是mTORC1，可感知特定的AA以及其他生理信号，包括胰岛素（能量状态的典型指标）。一旦AA确定mTORC1定位于溶酶体膜，胰岛素就在mTORC1信号传导中起关键作用，控制其激活。基于此分子模型，AA和胰岛素信号需要紧密协调以最大化牛奶蛋白的合成速率。泌乳奶牛的证据支持这种模型，其中胰岛素和糖原能增强了AA对牛奶蛋白质合成的作用。结合特定信号传导氨基酸的作用和能量源对利用吸收的氨基酸进行乳蛋白合成的不同作用似乎是营养需求系统中进一步提高泌乳奶牛日粮氮效率的明显步骤。