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

在像牛肉和奶牛这样的家养反刍动物中，饮食中提供的蛋白质含有生产肉类和牛奶等可食用产品所需的氨基酸。然而，将饲料蛋白质转化为牛奶或肉类蛋白质的效率很低，仅为15%至30%；换句话说，牛肉或奶牛消耗的大部分饲料蛋白质都以这样或那样的形式在粪便中排泄。粪便中蛋白质的过度排泄是不受欢迎的，原因有很多，包括：1)蛋白质补充剂价格昂贵，因此出于经济原因，动物有效利用它们很重要；2)粪便中的蛋白质排泄对环境构成威胁。反刍动物的消化道与非反刍动物(如猪)的不同之处在于，反刍动物的胃有四个隔室，前三个隔室是瘤胃、网状肌和皱胃(统称为前胃)。在前胃中，有一群非常多样化的微生物来发酵饲料。在某种程度上，食物蛋白质利用效率低下的原因是因为前胃中的微生物将食物中的大量蛋白质发酵成氨，然后氨被吸收到血液中。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排出。肝脏将氨转化为尿素，尿素是一种无毒的最终产品。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，因此对动物来说，氮(最初包含在食物蛋白质中)是不可逆转的损失。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来自己生长。这对动物有利，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，可以用于牛奶和肉类生产。这项研究计划的广泛目标是加强我们对是什么控制尿素从血液进入前胃的了解。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体和水通道蛋白，它们存在于前胃壁，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了这些蛋白质分子的活动。在这个研究项目中，我将研究这些蛋白质分子的活性如何受到饮食结构、前胃发酵产物和激素的影响。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，那么我们就可以开发出增加尿素从血流进入前胃的策略。这将提高集约化反刍动物生产系统的饲料蛋白质利用率和环境管理水平。

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.