Branched-chain amino acids degradation

Traditionally fermented dairy products have been used as beverages, meal components, and ingredients for many new products [60], The formation of flavor in fermented dairy products is a result of reactions of milk components lactose, fat, and casein. Particularly, the enzymatic degradation of proteins leads to the formation of key-flavor components that contribute to the sensory perception of the products [55], Methyl ketones are responsible for the fruity, musty, and blue cheese flavors of cheese and other dairy products. Aromatic amino acids, branched-chain amino acids, and methionine are the most relevant substrates for cheese flavor development [55]. Volatile sulfur compounds derived from methionine, such as methanethiol, dimethylsulflde, and dimethyltrisul-fide, are regarded as essential components in many cheese varieties [61], Conversion of tryptophan or phenylalanine can also lead to benzaldehyde formation. This compound, which is found in various hard- and soft-type cheeses, contributes positively to the overall flavor [57,62]. The conversion of caseins is undoubtedly the most important biochemical pathway for flavor formation in several cheese types [62,63]. A good balance between proteolysis and peptidolysis prevents the formation of bitterness in cheese [64,65],... 

Branched-Chain Amino Acids Are Not Degraded in the Liver... 

Vitamin B12 is essential for the methylmalonyl-CoAmutase reaction. Methylmalonyl-CoA mutase is required during the degradation of odd-chain fatty acids and of branched-chain amino acids. Odd-chained fatty acids lead to propionyl-CoA as the last step of P-oxida-tion. Methylmalonyl-CoA can be derived from propionyl-CoA by a carboxylase reaction similar to that of fatty acid biosynthesis. The cofactor for this carboxylation reaction is biotin, just as for acetyl-CoA carboxylase. The reaction of methylmalonyl-CoA mutase uses a free radical intermediate to insert the methyl group into the dicar-boxylic acid chain. The product is succinyl-CoA, a Krebs cycle intermediate. The catabolisms of branched-chain lipids and of the branched-chain amino acids also require the methylmalonyl-CoA mutase, because these pathways also generate propionyl-CoA. 

Figure 1. Dynamic utilization of amino acids in pigs. Degradation of essential amino acids via interorgan cooperation results in synthesis of nonessential amino acids. BCAA, branched-chain amino acids D3PG, D-3-phosphoglycerate (cm intermediate of glucose metabolism) HYP, hydroxyproline. Synthesis of serine from its carbon skeleton (D3PG) requires amino acids (e.g. aspartate and glutamate) as donors of the amino group.

Branched-chain amino acids are leucine, isoleucine and valine the increased concentrations are also consistent with an increased rate of degradation, as muscle protein contains a high proportion of these amino acids. The extent of the decrease in ATP concentration is even greater than in exaustive physical activity. Note the very large fall is glutamine concentration. 

In the branched-chain amino acids (Val, Leu, He) and also tyrosine and ornithine, degradation starts with a transamination. For alanine and aspartate, this is actually the only degradation step. The mechanism of transamination is discussed in detail on p. 178. 

The skeletal muscle is the most important site for degradation of the branched-chain amino acids (Val, Leu, lie see p. 414), but other amino acids are also broken down in the muscles. Alanine and glutamine are resynthesized from the components and released into the blood. They transport the nitrogen that arises during amino acid breakdown to the liver (alanine cycle see above) and to the kidneys (see p. 328). 

Figure 9-4. Metabolism of the branched-chain amino acids. The first two reactions, transamination and oxidative decarboxylation, are catalyzed by the same enzyme in all cases. Details are provided only for isoleucine. Further metabolism of isoleucine and valine follows a common pathway to propionyl CoA. Subsequent steps in the leucine degradative pathway diverge to yield acetoacetate. An intermediate in the pathway is 3-hydroxy-3-methylglutaryl CoA (HMG-CoA), which is a precursor for cytosolic cholesterol biosynthesis.

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

Increased uptake of branched-chain amino acids Muscle is the principal site for degradation of branched-chain amino acids (see... 

Free amino acids are further catabolized into several volatile flavor compounds. However, the pathways involved are not fully known. A detailed summary of the various studies on the role of the catabolism of amino acids in cheese flavor development was published by Curtin and McSweeney (2004). Two major pathways have been suggested (1) aminotransferase or lyase activity and (2) deamination or decarboxylation. Aminotransferase activity results in the formation of a-ketoacids and glutamic acid. The a-ketoacids are further degraded to flavor compounds such as hydroxy acids, aldehydes, and carboxylic acids. a-Ketoacids from methionine, branched-chain amino acids (leucine, isoleucine, and valine), or aromatic amino acids (phenylalanine, tyrosine, and tryptophan) serve as the precursors to volatile flavor compounds (Yvon and Rijnen, 2001). Volatile sulfur compounds are primarily formed from methionine. Methanethiol, which at low concentrations, contributes to the characteristic flavor of Cheddar cheese, is formed from the catabolism of methionine (Curtin and McSweeney, 2004 Weimer et al., 1999). Furthermore, bacterial lyases also metabolize methionine to a-ketobutyrate, methanethiol, and ammonia (Tanaka et al., 1985). On catabolism by aminotransferase, aromatic amino acids yield volatile flavor compounds such as benzalde-hyde, phenylacetate, phenylethanol, phenyllactate, etc. Deamination reactions also result in a-ketoacids and ammonia, which add to the flavor of... 

Maple Syrup Urine Disease Figure 18-28 shows the pathway for the degradation of branched-chain amino acids and the site of the biochemical defect that causes maple syrup urine disease. The initial findings that eventually led to the discovery of the defect in this disease were presented in three papers published in the late 1950s and early 1960s. This problem traces the history of the findings from initial clinical observations to proposal of a biochemical mechanism. 

Based on their results and their knowledge of the pathway shown in Figure 18-28, Dancis and coauthors concluded although it appears most likely to the authors that the primary block is in the metabolic degradative pathway of the branched-chain amino acids, this cannot be considered established beyond question. ... 

Protein degradation and amino acid metabolism are highly elevated in the diabetic, because the stimulatory effect of insulin on protein synthesis is nonexistent and the relative excess of glucagon and glucocorticoids causes protein breakdown to continue. Indeed, muscle wasting is a cardinal symptom of the untreated diabetic. Insulin also inhibits amino add release into the bloodstream, and this may be a reason a moderate rise in plasma amino add levels is observed in the diabetic. Such increased amino adds are largely of the branched-chain type, and alanine levels are in fact lower than normal. Nevertheless, alanine uptake by the liver is twice that of the normal individual, and it continues to be a major actor in the gluconeogenesis process. 

The liver is responsible for modifying blood protein and Aa composition, which it performs by a series of enzymatic process including transamination, deamination and reamination. The essential aromatic amino acids are degraded in the liver, whereas the branched-chain amino acids are passed to the periphery, where they are metabolised exclusively by skeletal muscle. Non-essential amino acids may be metabolised hepatically or in skeletal muscle. 

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. 

The degradation of the hranched-chain amino acids employs reactions that we have encountered previously in the citric acid cycle and fatty acid oxidation. Leucine is transaminated to the corresponding a-ketoacid, a-ketoisocaproate. This a-ketoacid is oxidatively decarboxylated to isovaleryl CoA by the branched-chain a-ketoacid dehydrogenase complex. 

The glucose-alanine cycle between the liver and the musculature is particularly significant. In muscle tissue, ammonia is generated during the degradation of amino acids (particularly the branched-chain amino acids). The transfer of ammonia to pyruvate yields alanine, which is then transported through the bloodstream to... 

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