The Molecular Regulation of Urea-Nitrogen Salvaging in Ruminants

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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.