Acetoacetate amino acid conversion

In mammals, muscle breakdown or excess protein intake results in an imbalance between the fates of the carbon chains and the amino nitrogen. Unlike fat (lipid storage) or glycogen (carbohydrate storage), excess amino acids are not stored in polymeric form for later utilization. The carbon chains of amino acids are generally metabolized into tricarboxylic acid (TCA) cycle intermediates, although it is also possible to make ketone bodies such as acetoacetate from some. Conversion to TCA intermediates is easy to see in some instances. For example, alanine is directly transaminated to pyruvate. 

Catabolism of tyrosine and tryptophan begins with oxygen-requiring steps. The tyrosine catabolic pathway, shown at the end of this chapter, results in the formation of fumaric acid and acetoacetic acid. Tryptophan catabolism commences with the reaction catalyzed by tryptophan-2,3-dioxygenase. This enzyme catalyzes conversion of the amino acid to N-formyl-kynurenine. The enzyme requires iron and copper and thus is a metalloenzyme. The final products of the pathway are acetoacetyl-CoA, acetyl-CoA, formic acid, four molecules of carbon dioxide, and two ammonium ions. One of the intermediates of tryptophan catabolism, a-amino-P-carboxymuconic-8-semialdehyde, can be diverted from complete oxidation, and used for the synthesis of NAD (see Niacin in Chapter 9). 

P-Hydroxybutyrate dehydrogenase (located in mitochondria) catalyses the conversion of acetoacetate to P-hydroxybutyrate. Acetone is formed by the spontaneous decarboxylation of acetoacetate (Fig. 1). Acetoacetate is also produced by degradation of the keto-plastic amino acids, leucine, isoleucine, phenylalanine and tyrosine. 

The amino acids leucine, isoleucine, phenylalanine, tryptophan, and tyrosine are capable of undergoing a metabolic conversion to acetoacetate, a ketone body. Thus, they are said to be ketogenic. 

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