Diamine alkaloids biosynthesis pathway

Tropane alkaloid biosynthesis has been studied at the biochemical level, and several enzymes from the biosynthetic pathway have been isolated and cloned, although the pathway has not been elncidated completely at the genetic level (Fig. 3b) (138). L-arginine is converted to the nonproteogenic amino acid L-omithine by the nrease enzyme arginase. Ornithine decarboxylase then decarboxylates ornithine to yield the diamine pntrescine. In Hyoscyamus, Duboisia, and Atropa, putrescine serves as the common precnrsor for the tropane alkaloids. 

Further work56 has now disproved this pathway, at least for sedamine. When [2-3H,6-14C]lysine was administered to Sedum acre the alkaloid incorporated both labels with an unchanged isotopic ratio. Thus, the hydrogen at C(2) of lysine is not lost in the biosynthesis as would be required for pathway a. An alternative sequence, path b (Scheme 16) satisfactorily accommodates the fresh evidence. Decarboxylation at C-2 now precedes rather than follows the oxidation step. To avoid the generation of a symmetrical diamine, the amino-group at C(6) is differentiated by methylation in the first step. 

In further consideration of the biosynthesis of the piperidine alkaloids the question of the significance of the incorporation of cadaverine must be answered. Accordingly further research has been directed to this point and it has been shown that cadaverine is a normal component of S. acre, that it is a specific precursor of sedamine (20), and that it is formed from lysine at the same time as sedamine. It follows then that any scheme for the biosynthesis of the piperidine alkaloids which does not accommodate cadaverine as a normal component is unrealistic An eminently reasonable hypothesis which fits all the evidence is shown in Scheme 1 it was anticipated in last year s Report. For those alkaloids derived from lysine without the intervention of a symmetrical intermediate, cadaverine formed by decarboxylation of lysine must remain enzyme-bound and therefore unsymmetrical. Exogenous cadaverine enters the pathway at this point by absorption on to the enzyme to give (29). In order to explain the incorporation of lysine into some alkaloids by way of a symmetrization step it is necessary only to postulate equilibration of bound with unbound cadaverine. The proposal that pyridoxal phosphate is involved in this pathway is more than mechanistically attractive, for L-lysinedecarboxylase (EC 4.1.1.18, L-lysine carboxy-lyase) and diamine oxidase [EC 1.4.3.6, diamine oxygen oxidoreductase (deaminating)], the two enzymes whose participation in the conversion of lysine into A -piperideine (30) is likely, both require pyridoxal phosphate as a co-factor. 

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