Vitamin C (ascorbic acid) physiology

维生素 C（抗坏血酸）生理学

• 批准号: 10697772
• 负责人: MARK A LEVINE
• 金额: $ 52.37万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697772
• 关键词: Affect; Animals; Area; Ascorbic Acid; Biochemistry; Cell physiology; Clinical; Coupled; Data Set; Diabetes Mellitus; Diet; Disease; Drug Kinetics; Eating; Erythrocytes; Fasting; Food; Foundations; Health; Heart; Human; Ingestion; Intake; Knowledge; Maintenance; Measures; Methodology; Methods; Modeling; Mole the mammal; Molecular Biology; Persons; Physiology; Plasma; Recommendation; Sampling; Techniques; Tissues; Vitamins; Work; fruits and vegetables; paracrine

Summary Vitamin C Physiology Rather than deficiency models, a concentration-function approach is a more rational method to determine vitamin intake recommendations for humans. At its heart, this approach relies on extensive and comprehensive characterization of vitamin physiology in healthy people. It is essential to have intensive and thorough datasets, as knowledge of normal physiology is a key to opening unexpected applications to health maintenance and disease treatment. Vitamin C is used as a model vitamin for this work. Physiology methodology, coupled to concentration-function relationships, also depends on understanding vitamin C biochemistry, molecular biology, and clinical pharmacokinetics. To study concentration-function and physiology relationships in humans for vitamin C, it is necessary to choose clinical samples that can be obtained easily; that contain the vitamin; and where changes in vitamin C concentration may affect physiology and/or cell function. For these reasons, one area of study is human red blood cells. As a prerequisite, we developed a new method to measure vitamin C in human red blood cells. This method is the foundation for exploring new functions of vitamin C in red blood cells in health and disease, with a major focus on diabetes. Humans, unlike most animals, cannot synthesize vitamin C and instead must obtain it from diet. Healthy humans who eat at least 5 servings of fruits and vegetables daily will obtain 200 mg or more of vitamin C. This will produce steady-state fasting plasma concentrations of 70 -80 moles per liter. Ingestion of more vitamin C from foods will not produce higher sustained concentrations. Even if a vitamin C supplement is taken, plasma concentrations will only rise transiently. All tissues, except red cells, accumulate vitamin C against its plasma concentration. However, once plasma concentrations reach 50 to 60 moles per liter, tissue concentrations are saturated and do not rise further. Thus, vitamin C concentrations are tightly controlled. We study mechanisms of how vitamin C is tightly controlled in animals and humans, and consequences of aberrancies in these mechanisms. We also study mechanisms and consequences of paracrine, or local, release of vitamin C.

总结 维生素C营养 与缺乏模型相比，浓度函数方法是确定人类维生素摄入量建议的更合理方法。在其核心，这种方法依赖于健康人群中维生素生理学的广泛和全面的表征。拥有密集和全面的数据集至关重要，因为正常生理学知识是开启健康维护和疾病治疗的意外应用的关键。维生素C被用作这项工作的模型维生素。生理学方法，加上浓度-功能关系，也取决于对维生素C生物化学，分子生物学和临床药代动力学的理解。 为了研究人体中维生素C的浓度-功能和生理学关系，有必要选择容易获得的临床样品;含有维生素;维生素C浓度的变化可能影响生理学和/或细胞功能。由于这些原因，研究的一个领域是人类红细胞。作为先决条件，我们开发了一种新的方法来测量人体红细胞中的维生素C。这种方法是探索维生素C在健康和疾病中红细胞新功能的基础，主要集中在糖尿病上。 与大多数动物不同，人类不能合成维生素C，而是必须从饮食中获得。健康的人每天至少吃5份水果和蔬菜，将获得200毫克或更多的维生素C。这将产生70 - 80摩尔/升的稳态空腹血浆浓度。从食物中摄取更多的维生素C不会产生更高的持续浓度。即使服用维生素C补充剂，血浆浓度也只会短暂升高。除红细胞外，所有组织都积累维生素C，而不是血浆浓度。然而，一旦血浆浓度达到每升50至60摩尔，组织浓度就饱和了，不再进一步上升。因此，维生素C浓度受到严格控制。我们研究了维生素C在动物和人类中是如何被严格控制的机制，以及这些机制中异常的后果。我们还研究了旁分泌或局部释放维生素C的机制和后果。