Glutamato Y Mtabolismo De La Glutamina

Glutamate and Glutamine in Metabolism

Glutamate, at the Interface between Amino Acid and Carbohydrate Metabolism1,2
John T. Brosnan
Department of Biochemistry, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada
ABSTRACT The liver is the major site of gluconeogenesis, the major organ of amino acid catabolism and the only organ with a complete urea cycle. These metaboliccapabilities are related, and these relationships are best exemplified by an examination of the disposal of the daily protein load. Adults, ingesting a typical Western diet, will consume 100 g protein/d; the great bulk of this is metabolized by the liver. Although textbooks suggest that these amino acids are oxidized in the liver, total oxidation cannot occur within the confines of hepatic oxygenuptake and ATP homeostasis. Rather, most amino acids are oxidized only partially in the liver, with the bulk of their carbon skeleton being converted to glucose. The nitrogen is converted to urea and, to a lesser extent, to glutamine. The integration of the urea cycle with gluconeogenesis ensures that the bulk of the reducing power (NADH) required in the cytosol for gluconeogenesis can be provided byancillary reactions of the urea cycle. Glutamate is at the center of these metabolic events for three reasons. First, through the well-described transdeamination system involving aminotransferases and glutamate dehydrogenase, glutamate plays a key catalytic role in the removal of -amino nitrogen from amino acids. Second, the “glutamate family” of amino acids (arginine, ornithine, proline,histidine and glutamine) require the conversion of these amino acids to glutamate for their metabolic disposal. Third, glutamate serves as substrate for the synthesis of N-acetylglutamate, an essential allosteric activator of carbamyl phosphate synthetase I, a key regulatory enzyme in the urea cycle. J. Nutr. 130: 988S–990S, 2000. KEY WORDS: glutamine
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gluconeogenesis

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urea synthesis

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liver metabolism

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dietary protein

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glutamate

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In considering relationships between glutamate and carbohydrate metabolism, this paper will focus exclusively on gluconeogenesis. However, for physiologic relevance, it is important not to consider glutamate alone, but glutamate in the context of the metabolism of all of theamino acids. Second, it is important not to consider gluconeogenesis alone, but other pathways with which it is integrated, in particular, the urea cycle. Therefore, this paper examines the metabolic disposal of the dietary protein load and considers the specific role of glutamate in this process under the following three headings: 1) the key role of glutamate and of glutamate dehydrogenase intransdeamination of amino acids; 2) the metabolism of the glutamate family of amino acids; and 3) the synthesis of N-acetylglutamate. The remarkable metabolic versatility of glutamate will also be discussed.

Metabolic disposal of dietary protein

1 Presented at the International Symposium on Glutamate, October 12–14, 1998 at the Clinical Center for Rare Diseases Aldo e Cele Dacco, Mario Negri ´Institute for Pharmacological Research, Bergamo, Italy. The symposium was sponsored jointly by the Baylor College of Medicine, the Center for Nutrition at the University of Pittsburgh School of Medicine, the Monell Chemical Senses Center, the International Union of Food Science and Technology, and the Center for Human Nutrition; financial support was provided by the International Glutamate TechnicalCommittee. The proceedings of the symposium are published as a supplement to The Journal of Nutrition. Editors for the symposium publication were John D. Fernstrom, the University of Pittsburgh School of Medicine, and Silvio Garattini, the Mario Negri Institute for Pharmacological Research. 2 Supported by a grant from the Medical Research Council of Canada.

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