Nutritional regulation of sulphur amino acid metabolism

硫氨基酸代谢的营养调节

• 批准号: RGPIN-2019-05400
• 负责人: House, James
• 金额: $ 4.01万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738249
• 关键词: Nutritional; regulation; sulphur; amino; acid

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).

长期目标：鉴于含硫氨基酸（SAA）在中间代谢和最佳生理功能中发挥的核心作用，了解调节动物含硫氨基酸（SAA）代谢的营养因素。对于这个NSERC发现补助金，我的小组将研究如何膳食蛋白质含量和质量（氨基酸组成），以及饮食来源的抗营养因子，影响SAA代谢时，维生素B6低于要求。背景技术背景：维生素B6（吡哆醛5 '-磷酸; PLP）是参与脂肪、碳水化合物和蛋白质代谢的100多种酶的重要辅因子，包括参与SAA代谢的那些酶。SAA蛋氨酸（在饮食中提供）通过两种B6依赖性酶，胱硫醚β合酶（CBS）和胱硫醚γ裂解酶（CGL）的作用转化为半胱氨酸。因此，B6缺乏会损害半胱氨酸的合成，影响蛋白质合成、谷胱甘肽的产生（氧化状态的调节剂）和硫化氢的产生。后者被认为是一种气体生物调节剂（gasotransmitter），在维持血管张力方面发挥重要作用，类似于一氧化氮。明显或严重的维生素B6缺乏症是罕见的，但中度缺乏症更为普遍（加拿大人口的25-30%），并且可能因饮食因素而加剧，包括常量营养素组成和抗营养因素（营养共同损伤）。 因此，了解影响B6状态和SAA代谢的因素将提高我们为所有动物（包括人类）提供营养供应的能力。 具体说明：使用我们实验室建立的边际维生素B6缺乏模型，将解决以下具体的研究问题：1）当SAA作为甲硫氨酸与甲硫氨酸+半胱氨酸的平衡供应时，半胱氨酸的可用性是否会受到限制并影响：a）蛋白质沉积; B）抗氧化状态和免疫功能;以及c）组织健康和完整性？ 2)亚麻籽消费，由于天然B6抑制剂的存在，影响维生素B6的状态和SAA代谢？3)SAA和B6状态受损将如何影响动物对特定炎症挑战的反应能力？研究计划的影响将通过以下方式得到认可：1）获得与调节关键营养素（SAA和B6）需求的因素有关的新知识; 2）增强对增加亚麻籽暴露的影响的理解; 3）HQP培训。 这项设计的研究计划将继续培训HQP（18个直接资助超过5年）在技术技能（高级营养分析;生物测定;饮食配方;实验设计和统计分析）和专业技能（沟通;与利益相关者互动）需要在学术界，牲畜饲养和人类营养事业（营养师;营养政策;食品开发）。