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

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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.****OBJECTIVES AND METHODS: The short-term objective is to determine the impact of oral L-arginine and D-arginine on their metabolic enzymes and pathways, and the basal levels of MG and AGEs. D-arginine, a MG scavenger but not a substrate for the various enzymes that use L-arginine, will serve as a control. The studies will be carried out in vivo in male and female Sprague-Dawley rats and in vitro in isolated tissues and organs collected from these rats. The protocol will examine the effects of acute single dose as well as chronic 4 or 16 week administration of L- and D-arginine. Two oral doses will be chosen from the lower and higher ends of the dose range reported in the literature. The long-term goal of my research program is to investigate the impact of these amino acids on carbohydrate and fatty acid metabolic pathways and on the molecular mechanisms of MG and AGEs generation, initially in animals (rats) and subsequently in human. Other amino acids of interest in my research program are cysteine and lysine, due to their great affinity for MG, and possible impact on the physiology of MG and AGEs formation.****OUTCOME: The results of my study will help to advance the knowledge on the physiological impact of oral L- and D-arginine, and other amino acids, and establish their metabolic fate in animals and humans. A beneficial interaction of arginine and cysteine with physiological processes of MG and AGEs formation may possibly encourage research examining fortification of normal diets with the amino acids studied.******