Lysine, catabolism

Neither nitrogen of lysine undergoes transamination. Metabolic diseases of lysine catabolism include periodic and persistent forms of hyperlysinemia-ammonemia. 

Revelles O, M Espinosa-Urgel, T Euhrer, U Sauer, JL Ramos (2005) Multiple and interconnected pathways for L-lysine catabolism in Pseudomonas putida KT2440. J Bacteriol 187 7500-7510. 

Revelles O, M Espinosa-Urgel, S Molin, JL Ramos (2004) The davDT operon of Pseudomonas putida, involved in lysine catabolism, is induced in response to the pathway intermediate 5-aminovaleric acid. J Bacterial 186 3439-3446. 

Ketoglutarate reductase catalyzes the formation of saccharopine from lysine, which is the first step in a major pathway for lysine catabolism. NADPH and a-ketoglutarate are cofactors in the reaction. 

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. 

Most prokaryotes employ dedicated PPTs active toward specific apoprotein substrates. Fungi also utilize separate PPTs for modification of the ACPs associated with the cytosolic and mitochondrial FAS systems, as well as the a-aminoadipate reductase involved in lysine biosynthesis [8]. The former is unusual in that it is a constituent domain of the multifunctional a-subunit (Fig. 4). Surprisingly, animals appear to employ a single PPT for servicing three different apoproteins the ACP domain of the cytosolic FAS, the ACP component of the mitochondrial FAS, and the a-aminoadipate semialdehyde dehydrogenase involved in lysine catabolism. The human PPT has recently been identified and characterized (S. Smith, 2003) and its crystal structure determined in complex with Mg, CoA, and the ACP domain of the cytosolic FAS (Structural Genomics Consortium). The ACP domain is comprised of a four-helix bundle, as are the ACPs associated with type II systems. The conserved serine residue that is the site of posttranslational modification lies at the N-terminal end of helix-2 (Fig. 6B), closely juxtaposed with the pyrophosphate of CoA that is cleaved during the phosphopantetheine transfer. Helix-2 makes multiple... 

C11H20N2O6, Mr 276.29, mp. 240-248°C (decomp.), [a] 3 +33 go (0.5 m HCl), +8.1 ° (0.5 m NaOH), pK 2.6, 4.1,9.2, 10.3. A widely distributed non-proteinogenic amino acid in Saccharomyces cerevisiae, Candida utilis, Lentinus edodes, Agaricus bisporus, tobacco leaves (Nicotiana tabacum), and other plants. Metabolism S. is a direct precursor of lysine in the biosynthesis and the first product of lysine catabolism. The responsible enzyme is saccharopine dehydrogenase (EC 1.5.1.8). S. is degraded to 2-aminoadipic acid... 

A few studies on lysine catabolism have been carried out in the Graminae. Nigam and McConnell (1963) infiltrated 3-week-old wheat seedlings with L-[ C]lysine and DL-a-amino[6- C]adipate and after 5 h extracted the tissue with ethanol. [ CJlysine gave rise to large amounts of labeled pipecolic acid and a-aminoadipate with glutamate as the next most labeled amino acid. This appears to imply that if Leistner et al, (1973) are correct, wheat must racemize the L-lysine in the course of metabolism. 

In fungi, although a-aminoadipaie is available fiom the lysine biosyniheTic pathway, it could also be obtained from a lysine catabolic pathway, similar to that fouiKl in the actinomycetes, and be channeled into penicillin biosynthesis. In keeping with this possibility, a lysine auxotroph of Pentdltium cfiryspgenum with a block before a-aminoadi-pate formation was found to produce penicillin in a lysine-supplemented medium, and it showed LAT activity (17). Therefore, in fungi, in addition to the lysine biosynthetic pathway, lysine catabolism may also provide a-aminoadipate for penicillin biosynthesis however, the relative contribution of each pathway is unclear. 

Madduri K, Stuttard C. Vining LC. Lysine catabolism in Streptomyces spp is primarily through cadaverinc 0-Lactam producers also make a-aminoadipate. j Bacteriol 1989 171 299-302. 

As the scheme shows, the various steps of lysine catabolism ate not all reversible and though they have all been demonstrated to occur in the rat this is not the case for Neurospora. 

Lysine catabolism begins with reductive amination of a-ketoglutarate to give saccharopine. Show the mechanism. 

The second step in lysine catabolism is oxidative deamination of sac-charopine to give a-aminoadipate semialdehyde. Show the mechanism. 

The formation of glutaric acid in the pathway of lysine catabolism was demonstrated by Borsook ef al. (157, 158) and by Rothstein and Miller (162). Borsook el oH. incubated L-a-aminoadipic-6-O acid with guinea pig liver homogenates and isolated from the deproteinized filtrates, after addition of carriers, radioactive a-ketoadipic acid as the ph ylhydrazone and glutaric acid, first as the barium salt and subsequently as the ciystalline free acid. The radioactive purity of both products were verified by the maintenance of constant specific activity on repeated recrystallizations. 

L-Lysine is an indispensable dibasic AA (L-2,6-diaminohexanoic add) required for hiunan growth and for maintaining nitrogen balance in adults. Lysine cannot be synthesized by the body, and therefore must be supplied through diet. Lysine and threonine are the only essential AAs whose amino gronps do not contiibnte to the total body amino pool because they do not participate in transamination reactions. Metabolites of lysine catabolism enter the TCA cycle only at the acetyl-CoA site, and therefore cannot serve as substrates for glucose synthesis. Consequently, lysine functions strictly as a ketogenic AA. ... 

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