Nicotine, methyl group precursor

Whereas many coenzymes form noncovalent complexes with their respective apoenzymes, various flavoenzymes are characterized by covalently bound FMN (25) or FAD (Fig. 3). Covalent linkage involves the position 8a methyl group or the benzenoid carbon atom 6 of the flavin and a cysteine or histidine residue of the protein. The covalent CN or CS bond can be formed by autoxidation of the noncovalent apoen-zyme/coenzyme precursor complex as shown in detail for nicotine oxidase (59). 

The biogenesis of nicotine has been studied in the plant with the aid of radioactive tracers. It was first shown that sodium formate is a precursor of the iV-methyl group of nicotine, but that methionine is a more immediate precursor since when these substances labeled with C are fed to the plant, the yield in radioactivity is greater with methionine than with formate (44). It was concluded that the methy-lation by methionine involved a true transmethylation and that the methyl group was not transferred via an intermediate oxidation to formate (44). This view found support in the results of an experiment involving the use of methionine with its methyl group doubly labeled with and deuterium. In this experiment, the ratio of the and... 

The use of methionine doubly labeled in the methyl group was subsequently extended to experiments with higher plants by Byerrum, Ball, and their co-workers. It was shown that the methyl group of methionine was a precursor of the N-methyl of nicotine in tobacco (Dewey et al., 1954), the methyl ether groups of lignin in barley and tobacco (Byerrum et al., 1954), and the methyl esters of pectinic acid in radish (Sato et ah, 1957). In none of these methylations was the deuterium ratio in... 

The formation of nicotinic acid—or, more precisely, of quinolinic acid—via two different pathways is an example of biochemical convergence, Now to the biosynthesis of the pyrrolidine ring of nicotine and nornicotine. Ornithine comes into play here. It furnishes the pyrrolidine component by the route already outlined, and this is then combined with nicotinic acid to give nicotine (Fig. 124). It is not known with certainty at what stage the methyl group is introduced. Very probably ornithine or putrescine is methylated and the methylated precursor is then icorporated into nicotine. Nicotine can be converted into nornicotine by demethyla-tion. 

In agreement with similar experiments on nicotine and hyoscyamine Datura metel) iV-methylputrescine (24) was a much better precursor for cuscohygrine and hyoscyamine in S. lurida than either putrescine or ornithine. [2- " C,(5- N]Omithine was incorporated into cuscohygrine with no loss of relative to and thus the nitrogen atom in cuscohygrine arises specifically from the 5-amino-group of ornithine. It was concluded from these data that decarboxylation and iV-methylation precede cyclisation to the N-methyl-pyrrolidine ring, with 5-Af-methylaminobutyraldehyde (25) or its cyclic form (26) as an intermediate a similar role for the latter compound has been demonstrated in nicotine biosynthesis. ... 

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