Lead acetate Lysine

Liver toxicity, as evidenced by alterations in the incorporation of lysine into liver proteins, was observed in rats administered 192 mg lead/kg/day by gavage as lead acetate for 9 weeks (Barratt et al. 1989). No effects were observed at 21 mg lead/kg/day. However, the toxicological significance of this finding is not known because neither serum enzymes nor histopathological evaluations were performed. 

Most remarkable for proving that structural relationships are not always what they seem are anatabine [(34) p. 11] and dioscorine (8). Inspection and experience with other piperidine alkaloids leads one to expect a biosynthesis for the piperidine ring [heavy bonding in (8)] from lysine via A -piperideine (3). However, in both cases it turns out that this ring derives from nicotinic acid [the exceptional derivation of the piperidine nuclei of coniine and pinidine (9) from acetate has been known for some time ]. 

The latter may be envisaged as an intermediate in the degradation of phenylalanine. In Clostridia catabolic breakdown of lysine (37) occurs by initial conversion to 6-lysine (38), (mediated by a 2,3-aminomutase) and thence via 3-keto-5-aminohexanoate to acetate and butyrate. An analogous catabolic sequence commencing with phenylalanine would lead to benzoic acid (as its CoA ester) and acetoacetate with the 6-aminophenylalanine (39) as an intermediate (Fig. 6). 

Fatty livers are also formed, in the presence of adequate choline, by diets deficient in amino acids other than methionine. This has been shown for threonine (SiNGAL et al. 1954) lysine and tryptophan (Vennart et al. 1958). Threonine deficiency, like choline deficiency, also leads to an increased synthesis of fatty acid from acetate (Yoshida and Harper 1960). An increase in synthesis has also been observed when cystine is added to a low protein diet. The relative importance of these effects for the formation of fatty livers is still uncertain. 

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