The Molecular Regulation of Urea-Nitrogen Salvaging in Ruminants

家畜如牛、绵羊和山羊被称为反刍动物。反刍动物消化系统的一个独特特征是存在四室胃，前三个室是瘤胃、网胃和重瓣胃（统称为前胃）。在前胃中，由于不同微生物群体的发酵活动，饮食营养物质发生广泛的胃前发酵。最重要的是，胃前发酵活动导致膳食含氮化合物转化为微生物蛋白，微生物蛋白是到达小肠的可代谢蛋白的主要组分，然后消化以产生必需氨基酸（EAA）供宿主动物使用。尽管存在于前胃中的微生物生态系统允许反刍动物将劣质、廉价的蛋白质来源（例如，尿素）转化为作为人类蛋白质主要来源的高质量动物产品（肉、奶），但将饲料氮转化为奶或肉的效率相对较差，仅为15- 30%。换句话说，反刍动物消耗的大部分膳食蛋白质都以粪便的形式排出，这对于经济和环境原因来说是不可取的。在某种程度上，膳食蛋白质利用率低的原因是膳食蛋白质在胃前发酵成氨，然后被吸收到血液中并在肝脏中转化为尿素。尿素主要通过尿液排出;然而，反刍动物已经进化出一种机制，允许血液中的尿素进入前胃，在那里它可以被微生物用作自身生长的氮源。这种进化适应被称为尿素氮回收（UNS）。然后微生物通过瘤胃，当它们在小肠中消化时，成为宿主动物EAA的重要来源。我的NSERC资助的研究项目的广泛目标是提高我们对UNS如何在反刍动物中调节的理解。我们目前的知识是，有两种类型的蛋白质分子被称为尿素转运蛋白（UT）和水通道蛋白（AQP），它们存在于前胃（和下消化道）的壁中，似乎负责尿素从血流进入前胃。然而，目前尚不清楚UT和AQP的功能如何调节。在我提议的研究中，我将研究UT和AQP的功能如何受到饮食组成、前胃和下消化道中的发酵终产物以及激素的影响。如果我们能够了解哪些营养或生理因素调节UT和AQP功能，那么我们就可以制定策略来增加尿素从血流进入前胃的通道。这将提高集约化反刍动物生产系统中饲料蛋白质的利用率和环境管理。

Domesticated livestock like cattle, sheep, and goats are referred to as ruminants. A unique feature of the ruminant's digestive system is the presence of a four-compartment stomach, with the first three compartments being the rumen, reticulum, and omasum (collectively referred to as the fore-stomachs). In the fore-stomachs, there is extensive pre-gastric fermentation of dietary nutrients that occurs due to the fermentative activities of a diverse microbial population. Of primary importance, the pre-gastric fermentative activities result in the conversion of dietary nitrogenous compounds into microbial protein, which is a major component of the metabolizable protein reaching the small intestine that is then digested to yield essential amino acids (EAA) for use by the host animal. Although the microbial ecosystem that exists in the fore-stomachs allows ruminants to convert poor quality, cheap protein sources (e.g., urea) into high quality animal products (meat, milk) that are major sources of protein for humans, the efficiency of converting feed nitrogen into milk or meat is relatively poor, at only 15-30%. In other words, most of the dietary protein that is consumed by ruminants is excreted in manure, which is undesirable for economic and environmental reasons. In part, the inefficiency of dietary protein utilization arises because of the pre-gastric fermentation of dietary protein to ammonia, which is then absorbed into the bloodstream and converted to urea in the liver. Urea is largely excreted in urine; however, ruminants have evolved a mechanism that allows urea in the bloodstream to pass into the fore-stomachs where it can be used by the microorganisms as a source of nitrogen for their own growth. This evolutionary adaptation is referred to as urea-nitrogen salvaging (UNS). The microorganisms then pass out of the rumen and become an important source of EAA for the host animal when they are digested in the small intestine. The broad objective of my NSERC-funded research program is to improve our understanding of how UNS is regulated in ruminants. Our current knowledge is that there are two types of protein molecules that are referred to as urea transporters (UT) and aquaporins (AQP) that are found in the wall of the fore-stomachs (and lower digestive tract) and appear to be responsible for the passage of urea from the bloodstream into the fore-stomachs. What is unknown, however, is how the function of UT and AQP is regulated. In my proposed research, I will study how the functions of UT and AQP are affected by diet composition, fermentational end-products in the fore-stomachs and lower digestive tract, and hormones. If we can understand what nutritional or physiological factors regulate UT and AQP function, then we can develop strategies to increase the passage of urea from the bloodstream into the fore-stomachs. This would improve the utilization of diet protein and environmental stewardship in intensive ruminant production systems.