The Molecular Regulation of Urea-Nitrogen Salvaging in Ruminants

像牛、绵羊和山羊这样的家畜被称为反刍动物。反刍动物消化系统的一个独特特征是有一个四室胃，前三个室是瘤胃、网状胃和瓣胃（统称为前胃）。在前胃中，由于多种微生物群的发酵活动，膳食营养物质在胃前进行广泛的发酵。最重要的是，胃前发酵活动导致膳食氮化合物转化为微生物蛋白，这是到达小肠的可代谢蛋白的主要组成部分，然后被消化产生必需氨基酸（EAA）供宿主动物使用。虽然存在于前胃中的微生物生态系统使反刍动物能够将劣质、廉价的蛋白质来源（如尿素）转化为人类主要蛋白质来源的优质动物产品（肉、奶），但将饲料氮转化为奶或肉的效率相对较低，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体外，这在经济和环境方面都是不可取的。在某种程度上，膳食蛋白质利用效率低下的原因是，膳食蛋白质在胃前发酵成氨，然后被吸收到血液中，在肝脏中转化为尿素。尿素大部分随尿液排出；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，微生物可以将其用作自身生长所需的氮源。这种进化适应被称为尿素-氮打捞（UNS）。然后，这些微生物从瘤胃中排出，在小肠中被消化，成为宿主动物EAA的重要来源。我的nserc资助的研究项目的主要目标是提高我们对反刍动物体内UNS是如何调节的理解。我们目前所知的是，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，似乎负责尿素从血液进入前胃。然而，UT和AQP的功能是如何调控的尚不清楚。在我的研究中，我将研究饮食成分、前胃和下消化道发酵终产物以及激素对UT和AQP功能的影响。如果我们能够了解是什么营养或生理因素调节了UT和AQP的功能，那么我们就可以制定策略来增加尿素从血液进入前胃的通道。这将提高集约化反刍动物生产系统中饲粮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.