BCKA dehydrogenase

Lombardo YB, Serdikoff C, Thamotharan M, Paul HS, and Adibi SA (1999) Inverse alterations of BCKA dehydrogenase activity in cardiac and skeletal muscles of diabetic rats. American Journal of Physiology 277, E685-92. 

Threonine can be broken down by tw o separate pathways. Serine dehydratase catalyzes the conv ersion of threonine to 2-ketobutyrate plus an ammonium ion 2-ketobutyrate is then converted by branched-chaln keto acid (BCKA) dehydrogenase to propionyl-CoA plus carbon dioxide. Propionyl-CoA catabolism is described later in this chapter. Threonine can also be broken down by a complex that has been suggested to be composed of threonine dehydrogerraseand acetoacetone synthase (Tressel ef al., 1986). Here, threonine catabolism results in the production of acetyl CoA plus glycure. 

Maple syrup urine disease is a genetic disease involving a defect in BCKA dehydrogenase. The disease affects one in 100,000 births, manifests in infants as leth-... 

The concept of sparing of one nutrient by another was introduced earlier, where it was demonstrated that dietary carbohydrate can spare protein. Similarly, cysteine can spare methionine and tyrosine can spare phenylalanine. A certain proportion of dietary methionine is converted to cysteine. Mediionine normally supplies part of the body s needs for cysteine. With cysteine-free diets, methionine can supply all of the body s needs for cysteine. The methionine catabolic pathway that leads to cysteine production is shown in Figure 8.27. Only the sulfur atom of methionine appears in the molecule of cysteine serine supplies the carbon skeleton of cysteine. a-Ketobutyrate is a byproduct of the pathway. a-Ketobutyrate is further degraded to propionyl-CoA by BCKA dehydrogenase or pyruvate dehydrogenase. Propionyl-CoA is then converted to succinyl-CoA, an intermediate of the Krebs cycle. 

The activity of BCAA aminotransferase is low in liver and relatively high in skeletal muscle. The opposite is true of the activity of BCKA dehydrogenase. This difference in enzyme activity is most likely the cause of the small extraction of BCAA by the liver. The majority of BCAA is taken up by skeletal muscles and converted to their respective branched-chain keto acids, which are partly consumed in the muscle cells. The remainder of BCKA is released into the blood. Part of the circulating BCKA is extracted by the liver. Inside the hepatocytes, BCKA is either degraded in the oxidative metabolic pathway or reaminated to preserve the total body content of BCAA (Harper et al., 1984). 

The branched-chain amino acids (BCAA He, Leu, Val) share the first two steps of their catabohsm. The first step is a reversible transamination. The resulting branched-chain a-keto acids (BCKA) are then oxidatively decarboxylized by the branched-chain a-keto-acid dehydrogenase (BCKDH). This step is irreversible and regulates the BCAA catabolism. The BCKDH activity is highly regulated and Leu seems to have the greatest impact on its activity (Harper etal., 984). The aim of the present study was to investigate the impact of excess levels of Leu on animal performance and BCAA catabolism. 

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