THE PHYSIOLOGICAL IMPACT OF AMINO ACID SUPPLEMENTS: INTERACTION WITH BASAL FORMATION OF ADVANCED GLYCATION ENDPRODUCTS

简介：精氨酸等氨基酸被许多健康人用作口服补充剂，但其生理影响尚未详细研究。精氨酸是一种基本的半必需氨基酸，部分来源于饮食。L-精氨酸参与几种代谢途径，是几种酶的底物，包括一氧化氮合酶，其形成一氧化氮、血管扩张剂和神经调节剂。它也转化为鸟氨酸，使氨解毒。肌酸是L-精氨酸的另一种代谢产物，促进Na+泵活性和中枢神经递质释放。精氨酸脱羧酶从L-精氨酸产生胍丁胺。口服精氨酸对这些代谢途径和酶的影响尚不清楚。我们已经证明，精氨酸的L-和D-异构体都是由葡萄糖和果糖代谢产生的反应性醛-丙酮醛（MG）。MG也是晚期糖基化终产物（AGEs）的主要前体。MG和AGEs在健康人中以低水平产生，并有助于正常的衰老过程。它们的水平在糖尿病状态下升高。该研究项目旨在提高我们对氨基酸补充剂（如精氨酸和半胱氨酸，另一种MG清除剂）对其代谢酶和途径以及基础MG和AGEs形成过程的影响的认识。该计划旨在将这些研究扩展到人类志愿者和人类生理学。

INTRODUCTION: Amino acids such as arginine are used as oral supplements by many healthy people, yet their physiological impact has not been studied in detail. Arginine is a basic semi-essential amino acid partly derived from the diet. L-arginine is involved in several metabolic pathways and is a substrate for several enzymes, including nitric oxide synthase, which forms nitric oxide, a vasodilator and neuromodulator. It is also converted to ornithine, which enables ammonia detoxification. Creatine, another metabolite of L-arginine, facilitates Na+ pump activity and central neurotransmitter release. Arginine decarboxylase produces agmatine from L-arginine. The impact of oral arginine on these metabolic pathways and enzymes is not known. We have shown that both L- and D-isomers of arginine scavenge methylglyoxal (MG), a reactive aldehyde generated by glucose and fructose metabolism. MG is also a major precursor of advance glycation endproducts (AGEs). MG and AGEs are produced at low levels in healthy people and contribute to the normal aging process. Their levels are elevated in diabetic states. The research project is designed to advance our knowledge on the impact of amino acid supplements, such as arginine and cysteine, another MG scavenger, on their metabolic enzymes and pathways and the process of basal MG and AGEs formation. The program aims to extend these studies to human volunteers and human physiology.