Translational regulation of milk protein synthesis

点击翻译按钮获取中文摘要

There are 960,600 dairy cows in Canada on 12,529 farms and they produce all the fluid milk consumed domestically. The cows’ diets are formulated by highly qualified nutritionists employed by feed companies or as independent consultants. One of the goals of ration formulation for dairy cows is to maximize the efficiency of dietary protein capture in milk. Cows typically consume over 4 kg/d of crude protein and secrete approximately 25% of that into milk. The 75% of protein intake that is not captured in milk is excreted as nitrogenous compounds in manure and represents both an environmental and financial loss. Protein capture efficiencies of up to 45% are possible but our understanding of how to consistently obtain such high efficiency is inadequate. The long-term goal of my research program is to improve understanding of the control of milk protein yield in the mammary glands of dairy cows so that responses to dietary manipulation can be predicted quantitatively. We have previously found that milk protein yields cannot be predicted from knowing the concentrations of amino acids in blood. Instead, it appears that factors that control the rate of mRNA translation into milk protein are important. These factors include the structure of the mRNA itself, and the activity state of certain proteins that bind to the mRNA. We will study both factors. We will use a cell-free translation assay to generate hypotheses about how mRNA structure accounts for differences in translational efficiency of the 4 caseins produced by cows, in both humans and cows. We will culture mammary epithelial cells with inhibitors of mRNA translational pathways to test their role in the nutritional activation of milk protein synthesis. The findings in cells and cell lysates will lead to tests in vivo, where we will inhibit signalling pathways in one udder half of cows by intramammary infusion of inhibitors, and evaluate how much they prevent the stimulation of milk protein yield by nutrients. These results will allow us to identify the pathways responsible for control of milk protein yield. The information will be used to parametize a computer model of milk protein synthesis that predicts protein yields on different diets. Efficient production of milk protein is desirable because the protein of milk supplies an ideal amino acid profile for infant growth. In addition, bioactive peptides derived from fermentation or digestion of milk proteins possess functional value in treatment and prevention of symptoms of the human metabolic syndrome including obesity, atherogenesis, arterial hypertension, and type 2 diabetes.