Isoleucine degradation and

Methionine metabolism Cysteine metabolism Valine, leucine, and isoleucine degradation... 

The long tail of myosin contains a high proportion of the amino acids leucine, isoleucine, aspartate and glutamate. These are released upon the degradation of myosin by intracellular proteases and peptidases and they provide nitrogen for the synthesis of glutamine. It is then stored in muscle and is a very important fuel for immune cells (Chapter 17). 

While MS-MS allows for unequivocal identification of most metabolites, there are a few exceptions. In particular, the short-chain acylcarnitines of 4 and 5 carbons represent more than one analyte. C4-Acylcarnitine is known to be a mixture of bu-tyrylcarnitine derived from fatty acid metabolism and isobutyrylcarnitine derived from the metabolism of valine (Fig. 3.2.3) [21, 58]. C5-Acylcarnitine is a mixture of isovalerylcarnitine and 2-methylbutyrylcarnitine derived from leucine and isoleucine degradation, respectively (Fig. 3.2.4) [20, 59]. Samples of patients treated with antibiotics containing pivalic acid may contain pivaloylcarnitine another C5 species... 

Maple syrup urine disease (branched-chain ketoaciduria) <0.4 Isoleucine, leucine, and valine degradation Branched-chain a-keto acid dehydrogenase complex Vomiting convulsions mental retardation early death... 

The carbon skeletons of methionine, isoleucine, threonine, and valine are degraded by pathways that yield suc-cinyl-CoA (Fig. 18-27), an intermediate of the citric acid cycle. Methionine donates its methyl group to one of several possible acceptors through S-adenosytmethionine,... 

The branched-chain amino acids (isoleucine, leucine, and valine), unlike the other amino acids, are degraded only in extrahepatic tissues. 

C-11) (1-9) Maple Syrup Urine Disease. There is a block in the degradation of the branched chain amino acids. Leucine, isoleucine, valine, and their ketoic acids are elevated in the blood and urine. Assays for these chemicals can be done in the laboratory. The urine acquires a maple syrup aroma. Infants with the condition have a variety of neurologic problems, including mental retardation. The condition is treated by dietary restriction of the affected amino acids. 

Isoleucine degradation. Isoleucine is degraded to acetyl CoA and succinyl CoA. Suggest a plausible reaction sequence, based on reactions discussed in the text, for this degradation pathway. 

AMINO ACIDS FORMING SUCCINYL-CoA Succinyl-CoA is formed from the carbon skeletons of methionine, isoleucine, valine, and threonine (as already discussed). An outline of the reactions that degrade the first three of these amino acids is illustrated in Figure 15.8. 

Some of the alanine released from skeletal muscle is derived directly from protein degradation. The carbon skeletons of valine, isoleucine, aspartate, and glutamate, which are converted to malate and oxaloacetate in the TCA cycle, can be converted to pyruvate and subsequently transaminated to alanine. The extent to which these amino acids contribute carbon to alanine efflux differs between different types of muscles in the human. These amino acids also may contribute to alanine efflux from the gut. 

The values of digestible amino acids in the intestine were calculated using the method proposed by Rulquin et al. (2001a and b). The values indicated in the present tables are not exactly the same as the values published in previous tables since the values of crude protein, amino acids, nitrogen degradability and RUP digestibility (TId) have all been updated. Nine essential amino acids have been taken into account lysine, methionine, leucine, histidine, phenylalanine, threonine, isoleucine, valine and arginine. 

Another example of a carboxylation reaction is the formation of oxaloacetate from pyruvate. Pyruvate carboxylase (EC 6.4.1.1) consists of 4 subunits, each covalently bound to one molecule of biotin and containing one Mg ion 1. Biotinyl-enzyme + ATP + CO2 + HjO — carboxybiotinyl-enzyme + ADP + Pj 2. Carboxybiotinyl-enzyme + pyruvate biotinyl-enzyme + oxaloacetate. In the degradation of fatty acids with odd numbers of C atoms, carboxylation of pro-pionyl-CoA to methylmalonyl-CoA is also catalysed by B. Carboxybiotinyl-enzyme + CHj-CHj-CO -SCoA biotinyl-enzyme + CHj-CH(COOH)-CO -SCoA. The same reaction occurs in the degradation of isoleucine, leucine and valine. 

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. 

Fig. 6.1. The L-leucine degradative pathway. Reactions for which inherited metabolic disorders have not been conclusively identified include A, leucine-isoleucine aminotransferase and the majority of the 3-methylglutaconic acidurias (6.6-6.7). 6.1, Branched-chain a-ketoacid dehydrogenase (BCKD) complex, a reaction also occurring in the initial steps of L-isoleucine and L-valine degradation 6.2, isovaleryl-CoA dehydrogenase 6.3, 3-methylcrotonyl-CoA carboxylase 6.4, 3-methylglutaconyl-CoA hydra-tase 6.8, HMG-CoA lyase. Pathologic urinary metabolites used as specific markers in the differential diagnosis are presented in squares. Abbreviation Co A, coenzyme A...

The evolution of tandem mass spectrometry (MS) for the analysis of acylcarnitines of blood and fibroblasts has been critical in the identification of previously unrecognized inborn errors of L-isoleucine degradation, 2-methylbutyryl-CoA dehydrogenase [11, 12] and 2-methyl-3-hydroxybutyr-yl-CoA dehydrogenase deficiencies [13]. 

Bacitracin is produced and marketed as a mixture of at least nine water-soluble peptides. The principal (60 —80%) component is bacitracin A [22601-59-8], C33H2Q3N2y02gS. The most probable stmcture of bacitracin A is shown in Figure 1 (67,73). Bacitracin B [1402-99-9] is similar to bacitracin A except that one of the isoleucines of bacitracin A is replaced by a valine. Bacitracin F [22601-63-4], is a relatively inactive degradation... 

Fatty acids with odd numbers of carbon atoms are rare in mammals, but fairly common in plants and marine organisms. Humans and animals whose diets include these food sources metabolize odd-carbon fatty acids via the /3-oxida-tion pathway. The final product of /3-oxidation in this case is the 3-carbon pro-pionyl-CoA instead of acetyl-CoA. Three specialized enzymes then carry out the reactions that convert propionyl-CoA to succinyl-CoA, a TCA cycle intermediate. (Because propionyl-CoA is a degradation product of methionine, valine, and isoleucine, this sequence of reactions is also important in amino acid catabolism, as we shall see in Chapter 26.) The pathway involves an initial carboxylation at the a-carbon of propionyl-CoA to produce D-methylmalonyl-CoA (Figure 24.19). The reaction is catalyzed by a biotin-dependent enzyme, propionyl-CoA carboxylase. The mechanism involves ATP-driven carboxylation of biotin at Nj, followed by nucleophilic attack by the a-carbanion of propi-onyl-CoA in a stereo-specific manner. 

---