Nutritional regulation of sulphur amino acid metabolism

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LONG-TERM OBJECTIVE: To understand the nutritional factors regulating sulphur amino acid (SAA) metabolism in animals, given the central role these amino acids play in intermediary metabolism and optimal physiological function. For this NSERC Discovery Grant, my group will be investigating how dietary protein content and quality (amino acid composition), as well as diet-derived anti-nutritive factors, impact SAA metabolism when vitamin B6 is present below requirements. BACKGROUND: Vitamin B6 (pyridoxal 5'-phosphate; PLP) is an important cofactor for over 100 enzymes involved in fat, carbohydrate and protein metabolism, including those involved in SAA metabolism. The SAA methionine (provided in the diet) is converted to cysteine through the action of two B6-dependent enzymes, cystathionine beta synthase (CBS) and cystathionine gamma-lyase (CGL). As such, a B6 deficiency impairs cysteine synthesis, with impacts on protein synthesis, glutathione production (regulator of oxidative status) and the production of hydrogen sulphide. The latter is recognized as a gaseous biological regulator (gasotransmitter) with important roles in maintaining vascular tone, akin to nitric oxide. Overt or severe vitamin B6 deficiency is rare, however moderate deficiency is more prevalent (25-30% of Canadian population), and can be exacerbated by dietary factors, including macronutrient composition and anti-nutritive factors (nutritional co-insults).  As such, understanding the factors impacting B6 status and SAA metabolism will enhance our ability to tailor nutrient supply to all animals, including humans. SPECIFIC OBJECTIVES: Using a model of marginal vitamin B6  deficiency established in our lab, the following specific research questions will be addressed: 1)When SAA are supplied as methionine vs. a balanced supply of methionine+cysteine, will cysteine availability be limited and impact: a) protein deposition; b) antioxidant status and immune function; and c) tissue health and integrity?  2)Will flaxseed consumption, due to the presence of a natural B6 inhibitor, impact vitamin B6 status and SAA metabolism? 3)How will compromised SAA and B6 status impact the ability of an animal to respond to specific inflammatory challenges? IMPACT OF THE RESEARCH PROGRAM: The impact of the research program will be recognized through: 1) the acquisition of new knowledge pertaining to factors regulating the requirements for key nutrients (SAA and B6); 2) enhanced understanding of the implications of increasing exposure to flaxseed; and 3) HQP training.  This designed program of study will continue to train HQP (18 directly funded over 5 years) in both technical skills (advanced nutrient analyses; bioassays; diet formulation; experimental design and statistical analyses) and professional skills (communication; interaction with stakeholders) needed for careers in academia, livestock feeding, and human nutrition careers (dietitians; nutrition policy; food product development).