The Catabolism of Lysine

The catabolism of lysine merges with that of tryptophan at the level of (3-ketoadipic acid. Both metabolic pathways are identical from this point on and lead to the formation of acetoacetyl-CoA (Figure 20.21). Lysine is thus ketogenic. It does not transaminate in the classic way. Lysine is a precursor of carnitine the initial reaction involves the methylation of e-amino groups of protein-bound lysine with SAM. The N-methylated lysine is then released proteolytically and the reaction sequence to carnitine completed. See Equation (19.6) for the structure of carnitine. 

Homoserine also has been detected in filtrates of liver preparations incubated with methionine. Cantoni provisionally identified homoserine as a product of the acid hydrolysis of active methionine (S-adeno-sylmethionine). Beyond homoserine, the postulated reactions 2 and 3 are still more speculative. It might be presumed that homoserine is oxidized to aspartic acid, in analogy to the observations on the catabolism of lysine, in which the analogous a-amino adipic acid is an intermediate. If aspartic acid is formed, the subsequent reaction sequence is readily apparent. Evidence favorable to the proposed reaction pathway is the finding of Marshall and Friedberg, of the occurrence of a small amount of fumaric acid, labeled in the methine carbons, from the livers of mice injected with DL-methionine-2-C. ... 

Neither the d- nor L-amino acid oxidase attack free lysine, but they can do so when the e-amino group is acetylated. It has been observed that the D N ratio of lysine isolated from the tissues was nearly the same as that of the labeled lysine fed, which shows that the a-hydrogen atom of lysine is not labile and that this amino acid cannot participate in the transaminase system. From the above it is evident that the catabolism of lysine is not initiated by a reaction which gives rise to the corresponding a-keto acid. This may be due to the fact that the e-amino group prevents lysine from being a suitable substrate for the enzymes that react with the a-amino group. 

Experimental evidence for the introduction of a-aminoadipic acid into the scheme for the catabolism of lysine was first reported by Borsook et al. (167,168). These investigators incubated L-lysine-6-C for 6 hr with guinea pig liver and precipitate any radioactive a-aminoadipic, along with glutamic acid, with Ba(OH)2 from alcoholic solution. The barium was removed and the free acid crystallized from HCl solution by addition of carrier a-aminoadipic acid. This material after the first recrystallization maintained a constant specific activity upon three subsequent recrystallizations. It was calculated that about 6 % of the radioactive ly e was converted to a-aminoadipic acid in the 6-hr incubation. 

An enzyme that catalyzes the reduction of A -piperidein-2-carboxylate to piperidine-2-car-boxylate (r-pipecolate) in the catabolism of o-lysine by Pseudomonas putida ATCC12633 is an NADPH-dependent representative of a large family of reductases that are distributed among bacteria and archaea (Muramatsu et al. 2005). It also catalyzes the reduction of A -pyrrolidine-2-carboxylate to L-proline. 

Muramatsu H, H Mihara, R Kakutani, M Yasuda, M Ueda, T Kurihara, N Esaki (2005) The putative malate/ lactate dehydrogenase from Pseudomonas putida is an NADPH-dependent ALpiperideine-2-carboxyl-ate/A -pyrroline-2-carboxylate reductase involved in the catabolism of L-lysine and D-proline. J Biol Chem 280 5329-5335. 

Transamination is of central importance in amino acid metabolism, provid-ingpathwaysforthe catabolism of aU amino acids other than lysine (which does not undergo transamination), although pathways other than transamination may be more important for the catabolism of some amino acids. It also provides a pathway for the synthesis of those amino acids for which there is an alternative source of the oxo-acid (the nonessential amino acids). As can be seen from Table 9.3, many of the oxo-acids are common metabolic intermediates. 

This chapter focuses initially on the catabolism of the amino acids. Aminotransferases can be used to catalyse the first step in the breakdown of nearly all of the amino acids. Lysine catabolism, in contrast, does not begin with an aminotrans-feraseamino acids can be catabolized via more than one pathway. Glutamate catabolism, for example, can begin by reactions catalyzed by glutamate oxaloacetate aminotransferase or glutamate dehydrogenase. 

Leucine and lysine are purely ketogenic amino adds. The catabolism of these amino acids does not yield intermediates of the Krebs cycle. It does not yield pyruvate. It does not produce compoimds that can result in the net synthesis of glucose. Leucine catabolism results in the production of a molecule of acetyl-CoA and a molecule of acetoacetate lysine breakdown produces acetoacetyl-CoA. 

Catabolism of lysine would have resulted in complete loss of the at position 4. 

Some 2% of lysine residues in low-density lipoproteins (LDL) of plasma were glycosylated in euglycemia and up to 5% in the outpatient diabetic (S9) with modification of some 2-5% lysine residues, the catabolism of LDL was decreased by 5 to 25% (S40). In poorly controlled diabetics, the decrease in LDL catabolism in diabetics could produce an 8-27% reduction in LDL cholesterol (A4). 

Although fatty acid oxidation is usually the major source of ketone bodies, they also can be generated from the catabolism of certain amino acids leucine, isoleucine, lysine, tryptophan, phenylalanine, and tyrosine. These amino acids are called keto-genic amino acids because their carbon skeleton is catabolized to acetyl CoA or acetoacetyl CoA, which may enter the pathway of ketone body synthesis in liver. Leucine and isoleucine also form acetyl CoA and acetoacetyl CoA in other tissues, as well as the liver. 

The pathways involved in the catabolism of the individual amino acids range from one-step reactions, such as with aspartate, glutamate, and alanine, which use the appropriate amino transferases, to multistep pathways of the aromatic amino acids and lysine (e.g., tyrosine is degraded in four steps to acetoacetate and fumarate). 

The amino group of threonine, like that of lysine, is not available for reversible transfer reactions. Thus, the from other amino acids is not found in threonine - and the C N ratio of threonine, like that of serine, isolated from body tissues, shows only small differences in the dilution of the two labels. The explanation for this is that the catabolism of threonine by way of glycine does not involve loss of the amino group. ... 

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