Amino acid degradation transamination

See also Amino Acid Degradation, Transamination in Amino Acid Metabolism... 

The alanine cycle accomplishes the same thing as the Cori cycle, except with an add-on feature (Fig. 17-11). Under conditions under which muscle is degrading protein (fasting, starvation, exhaustion), muscle must get rid of excess carbon waste (lactate and pyruvate) but also nitrogen waste from the metabolism of amino acids. Muscle (and other tissues) removes amino groups from amino acids by transamination with a 2-keto acid such as pyruvate (oxaloacetate is the other common 2-keto acid). 

Equilibrium of transamination reactions For most transamina tion reactions, the equilibrium constant is near one, allowing the reaction to function in both amino acid degradation through removal of a-amino groups (for example, after consumption of a protein-rich meal), and biosynthesis through addition of amino groups to the carbon skeletons of a-keto acids (for example, when the supply of amino acids from the diet is not adequate to meet the synthetic needs of cells). 

Aldehydes related to common amino acids (3-methylbutanal from leucine, 2-methylpropanal from valine, phenylacetaldehyde from phenylalanine) are formed by enzymatic decarboxylation of the corresponding keto acids, which in turn are reversibly related to the amino acids by transamination [i.e., the keto acids are both degradation products of amino acids 147, 148) and intermediates in their synthesis 149). A third possibility—non-enzymatic oxidation of amino acids to aldehydes by enzymatically produced o-quinones—is established 150, 151) but is not discussed here. 

Isoleucine and valine. The first four reactions in the degradation of isoleucine and valine are identical. Initially, both amino acids undergo transamination reactions to form a-keto-/T methyl valerate and a-ketoiso valerate, respectively. This is followed by the formation of CoA derivatives, and oxidative decarboxylation, oxidation, and dehydration reactions. The product of the isoleucine pathway is then hydrated, dehydrogenated, and cleaved to form acetyl-CoA and propionyl-CoA. In the valine degradative pathway the a-keto acid intermediate is converted into propionyl-CoA after a double bond is hydrated and CoA is removed by hydrolysis. After the formation of an aldehyde by the oxidation of the hydroxyl group, propionyl-CoA is produced as a new thioester is formed during an oxidative decarboxylation. 

In general, amino acid degradation begins with deamination. Most deamination is accomplished by transamination reactions, which are followed by oxidative deaminations that produce ammonia. Although most deaminations are catalyzed by glutamate dehydrogenase, other enzymes also contribute to ammonia formation. Ammonia is prepared for excretion by the enzymes of the urea cycle. Aspartate and CO, also contribute atoms to urea. 

The first stage of amino acid degradation, the removal of the a-amino group, is usually accomplished by a transamination reaction. Transaminases catalyze the transfer of the a-amino group from an a-amino acid to an a-keto acid ... 

See also Metabolic Nitrogen Balance, Transamination in Amino Acid Metabolism, Amino Acid Degradation, Urea Cycle, Ammonia Transport in the Body, De Novo Pyrimidine Nucleotide Metabolism (from Chapter 22). 

Overall, in a transamination reaction, an amino group from one amino acid becomes the amino group of a second amino acid. Because these reactions are readily reversible, they can be used to remove nitrogen from amino acids or to transfer nitrogen to a-keto acids to form amino acids. Thus, they are involved both in amino acid degradation and in amino acid synthesis. 

Amino acid degradation is important for the synthesis of volatile compounds and the transamination of some amino acids methionine, branched-chain, and aromatic amino acids. Transamination is the main degradation pathway that leads to the formation of a-keto acids, which are then degraded into various aromatic compounds. The conversion of amino acids to keto- and hydroxyl acids is initiated by lactobacilli, and Lactococcus strains further convert these products to carboxylic acid. This cooperation between LAB and non-starter LAB can enhance cheese flavor. 

Removal of a-amino nitrogen by transamination (see Figure 28-3) is the first catabolic reaction of amino acids except in the case of proline, hydroxyproline, threonine, and lysine. The residual hydrocarbon skeleton is then degraded to amphibolic intermediates as outhned in Figure 30-1. 

During the degradation of most amino acids, the a-amino group is initially removed by transamination or deamination. Various mechanisms are available for this, and these are discussed in greater detail in B. The carbon skeletons that are left over after deamination undergo further degradation in various ways. 

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 active form of vitamin Be, pyridoxai phosphate, is the most important coenzyme in the amino acid metabolism (see p. 106). Almost all conversion reactions involving amino acids require pyridoxal phosphate, including transaminations, decarboxylations, dehydrogenations, etc. Glycogen phosphory-lase, the enzyme for glycogen degradation, also contains pyridoxal phosphate as a cofactor. Vitamin Be deficiency is rare. 

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.

Many other amino acids are degraded in similar ways. In most cases the sequence is initiated by transamination to the corresponding 2-oxoacid. Beta oxidation and breakdown to such compounds as pyruvate and acetyl-CoA follows. 

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