Biochemistry of Amino Acids - A. Master 1961

Intermediary Metabolism of Amino Acids
Lysine
Catabolism of Lysine

As is known, lysine is an essential amino acid in mammalian Nutrition (Table 10). In the diet of growing rats, lysine cannot be replaced by either $\alpha$-aminoadipic acid [1038] or $\alpha$-amino-$\varepsilon$-guanidinocaproic acid [1039]. Unlike Other Amino Acids, L-lysine cannot be replaced in dietary regimens by its D-isomer [1040, 1041] or by derivatives of the L-isomer in which the $\alpha$-amino group bears a substituent or is replaced by a hydroxy group. Meanwhile, $\varepsilon$-N-acetyl- and $\varepsilon$-N-methyllysine can replace lysine in the diet for rat growth [1042, 1043]. When rats are fed lysine labeled with N¹⁵ and deuterium, the D : N¹⁵ ratio in the lysine incorporated into organ Proteins remains unchanged [1044]. Upon administration of N¹⁵-ammonium or N¹⁵-amino acids to rats, the isotopic nitrogen is not transferred to the $\alpha$-amino group of lysine [270, 1045]. Only very weak labilization of the $\alpha$-hydrogen atom of lysine is observed in the rat Organism. All these data indicate that lysine does not take any significant part in reversible Transamination or deamination processes; however, they do not rule out the possibility of irreversible deamination or transamination of this amino acid.

Borsuk and co-workers [1046–1048] observed The conversion of lysine into glutaric acid. They found that in guinea pig Liver homogenates, $\varepsilon$-C¹⁴-lysine is converted into $\alpha$-aminoadipic acid; the latter is transformed into $\alpha$-ketoadipic acid, which in turn undergoes decarboxylation to form glutaric acid:

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It is possible that reaction (2) proceeds via transamination.

The formation of glutaric acid from lysine can be considered established; Ringer and co-workers [1050] as early as 1913 suggested the existence of such a transformation, based on the fact that neither lysine nor glutaric acid is converted into glucose or acetoacetic acid in the animal body. Rotstein and Miller, using the isotope-trap technique, demonstrated in experiments on rats the conversion of lysine into glutaric acid and of glutaric acid into L-$\alpha$-hydroxyglutaric acid; the latter is further oxidized to $\alpha$-ketoglutaric acid; furthermore, the $\varepsilon$-carbon atom of lysine can be partially converted into formate. These data indicate the possibility of lysine conversion into glutamic acid, which is consistent with the findings of other authors obtained in studies with $\varepsilon$-C¹⁴-lysine [1049, 1051, 1055]. The presence of pipecolic acid in the Tissues of A number of plants [1025, 1056–1059] and the detection of the conversion of lysine into pipecolic acid in higher plants [1071, 1072], in Neurospora [1023], and in the rat organism [1051] have served as an indication that pipecolic acid is an intermediate in lysine METABOLISM. According to Rotstein and Miller, in the rat organism during the conversion of lysine into pipecolic acid, the $\alpha$-amino group is eliminated rather than the $\varepsilon$-amino group of lysine. It was found that pipecolic acid is among the major metabolic products of lysine in rats; it apparently represents an intermediate in the conversion of lysine into $\alpha$-aminoadipic acid. These studies showed that during the degradation of lysine in the rat organism, The transfer of nitrogen from the $\varepsilon$-amino group of lysine to the $\alpha$-amino group of $\alpha$-aminoadipic acid is accomplished As a result of an intramolecular transamination reaction (see scheme on p. 432) [1052, 1055]. It should be borne in mind that although the scheme given below is consistent with known facts concerning The process of lysine dissimilation, individual steps of this process require experimental clarification. The conversion of lysine into $\alpha$-keto-$\varepsilon$-aminocaproic acid (or its cyclic form, $\Delta^1$-piperidinocarboxylic acid) has not yet been achieved in experiments with enzyme preparations from mammalian tissues. Snake venom L-Amino Acid Oxidase catalyzes this reaction at a very low rate. When the $\varepsilon$-amino group of lysine is blocked, for example, by the Introduction of a carbobenzoxy group, The oxidation of the $\alpha$-amino group proceeds much faster. As a result of this reaction, the $\varepsilon$-N-carbobenzoxy derivative keto acid is formed. After removal of the protecting group, the keto acid ($\alpha$-keto-$\varepsilon$-aminocaproic acid) is obtained, which in solution exists in equilibrium with its cyclic form [1060] (p. 237). The formation of this compound in Neurospora was discovered by Schwit et al. [1021–1023], who observed the conversion of lysine into $\Delta^1$-piperidine-2-carboxylic acid. The possible participation of $\Delta^1$-amino group derivatives of lysine in its metabolism should be taken into account, especially in connection with the data showing that $\varepsilon$-N-acetyl and $\varepsilon$-N-methyl derivatives of lysine can replace lysine in the nutrition of growing rats. Moreover, it is known that the enzymatic deamination reactions of D- and L-lysine and the transamination of the $\alpha$-amino group of L-lysine proceed significantly faster if the $\alpha$-amino group is blocked [1060, 1061]. Similar observations exist regarding Ornithine derivatives. It is noteworthy that $\alpha$-N-acetylornithine participates in one of the Metabolic pathways of ornithine (p. 344).

In experiments with a fraction of rat liver homogenate, the conversion of $\Delta^1$-piperidine-2-carboxylic acid into L-pipecolic acid was detected; reduced di- or triphosphopyridine nucleotide is required for this reaction [1142]:

In rats, ε-C¹⁴-D-lysine is not converted into D-pipecolic acid; all of the isotopic carbon administered as lysine was recovered in the urine and non-protein nitrogen fractions of tissues [1062].

Fig. 22. Summary scheme of lysine transformations.

Neuberger and Sanger [1061] were the first to suggest that δ-aminovaleric acid is one of the products of lysine metabolism. It has been established that this amino acid is formed by the decarboxylation of the α-keto analogue of lysine [1060]. According to Rothstein and Miller [1063], δ-C¹⁴-5-aminovaleric acid is converted into glutamic acid in rats. δ-Aminovaleric acid can undergo transamination [1064, 1065] (p. 227); this reaction is expected to yield glutaric acid semialdehyde, which can be further oxidized to glutaric acid.

Lysine has been found in bound form in Yeast, specifically as ε-N-biotinyl-L-lysine (biocytin) [1066]. The existence of a compound containing lysine bound via its ε-amino group is of considerable interest; there is also other evidence supporting the existence of compounds involving bonds through the ε-amino group of lysine (p. 0229). Wright et al. [1067] detected an enzyme in human Blood that hydrolyzes biocytin. Biocytin is excreted in the urine as biocytin sulfoxide [1068].

Data on the metabolism of 5-hydroxylysine are scant (p. 50). This amino acid has been found only in Collagen [1069]. Upon analysis of gelatin and Skin collagen hydrolysates isolated from young rats fed C¹⁴-lysine for three weeks, the radioactive carbon content was found to be identical in both lysine and hydroxylysine. These findings suggest that lysine is a precursor of hydroxylysine [1070].