Branched-Chain Amino Acid Metabolism: Implications for Establishing Safe Intakes

Abstract

There are several features of the metabolism of the indispensable BCAAs that set them apart from other indispensable amino acids. BCAA catabolism involves 2 initial enzymatic steps that are common to all 3 BCAAs; therefore, the dietary intake of an individual BCAA impacts on the catabolism of all 3. The first step is reversible transamination followed by irreversible oxidative decarboxylation of the branched-chain alpha-keto acid transamination products, the branched chain alpha-keto acids (BCKAs). The BCAA catabolic enzymes are distributed widely in body tissues and, with the exception of the nervous system, all reactions occur in the mitochondria of the cell. Transamination provides a mechanism for dispersing BCAA nitrogen according to the tissue's requirements for glutamate and other dispensable amino acids. The intracellular compartmentalization of the branched-chain aminotransferase isozymes (mitochondrial branched-chain aminotransferase, cytosolic branched-chain aminotransferase) impacts on intra- and interorgan exchange of BCAA metabolites, nitrogen cycling, and net nitrogen transfer. BCAAs play an important role in brain neurotransmitter synthesis. Moreover, a dysregulation of the BCAA catabolic pathways that leads to excess BCAAs and their derivatives (e.g., BCKAs) results in neural dysfunction. The relatively low activity of catabolic enzymes in primates relative to the rat may make the human more susceptible to excess BCAA intake. It is hypothesized that the symptoms of excess intake would mimic the neurological symptoms of hereditary diseases of BCAA metabolism.

Aspectos atuais sobre aminoácidos de cadeia ramificada e exercício físico

“…Desse modo, a transaminação dos ACR fornece mecanismos para transferir o nitrogênio dos ACR de acordo com a necessidade do tecido por glutamato e outros aminoácidos não-essenciais. Além disso, cabe ressaltar que as isoenzimas ATACR em mamíferos são muitos específicas para ACR e glutamato, sendo a preferência de substratos a seguinte: isoleucina > valina >> glutamato (Cynober, Harris, 2006;Harris et al, 2005;Hutson, Sweatt, Lanoue, 2005;Harris, Joshi, Jeoung, 2004).…”

“…Desse modo, a transaminação dos ACR fornece mecanismos para transferir o nitrogênio dos ACR de acordo com a necessidade do tecido por glutamato e outros aminoácidos não-essenciais. Além disso, cabe ressaltar que as isoenzimas ATACR em mamíferos são muitos específicas para ACR e glutamato, sendo a preferência de substratos a seguinte: isoleucina > valina >> glutamato (Cynober, Harris, 2006;Harris et al, 2005;Hutson, Sweatt, Lanoue, 2005;Harris, Joshi, Jeoung, 2004).Posteriormente à reação catalisada pela enzima ATACR e à conseqüente formação dos cetoácidos de cadeia ramificada, esses podem sofrer descarboxilação oxidativa mediada pelo complexo enzimático DCCR -presente na superfície interna da membrana interna mitocondrial. Por meio da reação catalisada pelo complexo DCCR, os cetoácidos de cadeia ramificada KIC, KMV e KIV são convertidos em isovaleril-CoA, 3-metilbutiril-CoA e isobutiril-CoA, respectivamente.…”

Branched-chain Amino Acid Metabolon

“…The forward nitrogen transfer is favored by oxidation of the BCKA products by BCKDC. Net nitrogen transfer from BCAAs to glutamate occurs when the carbon skeleton of the BCAA is irreversibly lost via the BCKDC step (oxidation) (11).…”

Regulation of the plasma amino acid profile by leucine via the system L amino acid transporter

“…The branched-chain amino acids (BCAAs), leucine, isoleucine, and valine, cannot be synthesized endogenously in mammals, 1) and are therefore classified as nutritionally essential or indispensable amino acids. Mounting evidence indicates that BCAAs have various physiological and metabolic functions.…”

“…Mounting evidence indicates that BCAAs have various physiological and metabolic functions. 1,2) It has been reported that intake of individual or combined BCAAs 3,4) or ingestion of proteins 5) affects the plasma amino acid profile. In addition of acute changes in the plasma amino acid profiles associated with ingestion of amino acids and proteins, the plasma amino acid profile has been the focus of increasing attention because of its prospective application in the diagnosis and assessment of disease and pathophysiological states.…”