Functional roles and regulation of gastrointestinal transporter proteins in urea-nitrogen salvaging in ruminants

在家养反刍动物如肉牛和奶牛中，饮食中提供的蛋白质含有生产可食用产品如肉和奶所需的氨基酸。然而，将膳食蛋白质转化为牛奶或肉类蛋白质的效率很低，只有15%至30%;换句话说，肉牛或奶牛消耗的大部分膳食蛋白质以某种形式排泄在粪便中。由于多种原因，粪便中的这种过量的饮食蛋白质排泄是不期望的，包括：1）蛋白质补充剂是昂贵的，因此出于经济原因，动物有效地利用它们是重要的;以及2）粪便中的蛋白质排泄对环境构成威胁。反刍动物的消化道不同于非反刍动物的消化道（例如，反刍动物的胃（猪）具有四个隔室，前三个隔室是瘤胃、网胃和重瓣（统称为前胃）。在前胃中，有非常多样化的微生物群体发酵饲料。在某种程度上，膳食蛋白质利用率低的原因是前胃中的微生物将大量膳食蛋白质发酵成氨，然后被吸收到血液中。氨对动物是有毒的，所以当前胃的血液通过肝脏时，基本上所有的氨都被肝脏清除。肝脏将氨转化为尿素，这是一种无毒的最终产品。在肝脏中产生的尿素被释放到血液中，其中大部分最终被排泄到尿液中，因此代表了氮（最初包含在膳食蛋白质中）对动物的不可逆损失。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于自身的生长。这对动物有益，因为这些微生物最终从前胃进入小肠，在那里它们被动物的酶消化，产生氨基酸，然后被吸收，可用于牛奶和肉类生产。这项研究计划的广泛目标是提高我们对尿素从血液进入前胃的控制因素的理解。目前我们所知道的是，有两种类型的蛋白质分子被称为尿素转运蛋白和水通道蛋白，它们存在于前胃的壁中，似乎负责尿素从血流进入前胃;然而，我们不知道是什么控制着这些蛋白质分子的活性。在这个研究项目中，我将研究这些蛋白质分子的活性是如何受到饮食成分、前胃发酵产物和激素的影响的。如果我们能够了解哪些营养或生理因素调节这些蛋白质分子的活性，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料蛋白质的利用率和环境管理。

In domesticated ruminants like beef and dairy cattle, the protein that is provided in the diet contains amino acids that are required for the production of edible products like meat and milk. However, the efficiency of converting dietary protein into milk or meat protein is poor at only 15 to 30%; in other words, most of the dietary protein that is consumed by beef or dairy cattle is excreted in the manure in one form or another. This excessive excretion of diet protein in the manure is undesirable for a number of reasons, including: 1) protein supplements are expensive, so it is important for economic reasons that animals use them efficiently; and 2) protein excretion in manure poses a threat to the environment. The ruminant digestive tract is different from that of non-ruminants (e.g., pigs) in that ruminants possess 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 a very diverse population of microorganisms that ferments the feed. In part, the inefficiency of dietary protein utilization arises because microorganisms in the fore-stomachs ferment a lot of the dietary protein to ammonia, which is then absorbed into the bloodstream. Ammonia is toxic to the animal, so essentially all of the ammonia is removed by the liver when blood from the fore-stomachs passes through the liver. The liver converts ammonia to urea, which is a non-toxic end-product. Urea that is produced in the liver is released into the bloodstream and most of it ends up being excreted in the urine, thus representing an irreversible loss of nitrogen (originally contained in dietary protein) to the animal. 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 for their own growth. This benefits the animal because these microorganisms eventually pass out of the fore-stomachs to the small intestine where they are digested by the animal’s enzymes to yield amino acids that are then absorbed and can be used for milk and meat production. This research program’s broad objective is to enhance our understanding of what controls the passage of urea from the bloodstream into the fore-stomachs. What we know at this time is that there are two types of protein molecules that are referred to as urea transporters and aquaporins that are found in the wall of the fore-stomachs and appear to be responsible for the passage of urea from the bloodstream into the fore-stomachs; however, we do not know what controls the activity of these protein molecules. In this research program, I will study how the activity of these protein molecules is affected by the composition of the diet, the products of fermentation in the fore-stomachs, and hormones. If we can understand what nutritional or physiological factors regulate the activity of these protein molecules, 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.