NICOTINE BIOSYNTHESIS

Nicotine biosynthesis

Nicotine biosynthesis pathway involves the reaction of cyclic coupling between the two structures that make up the nicotine. Metabolic studies indicate that the pyridine ring of nicotine from nicotinic acid while pyrrolidone is derived from the N-methyl-Δ1-pyrrollidium cations. Biosynthesis of two structural components results in two independent synthesis, NAD pathway for nicotinic acid and tropane pathway for N-methyl-Δ1-pyrrollidium cations.

NAD pathway in the genus nicotiana starting with aspartic acid oxidation to α-imino succinate by aspartate oxidase (AO). This is followed by condensation with glyceraldehyde-3-phosphate and cyclization catalyzed by quinolinate synthase (QS) to give quinolinic acid. Quinolinic acid then reacts with the acid-catalyzed pyrophosphate phosphoriboxyl quinolinic phosphoribosyl transferase (QPT). The reaction is now underway through the cycle to produce NAD rescue by converting nicotinamide nicotinic acid by the enzyme nicotinamidase.

Cation N-methyl-Δ1-pyrrollidium used in the synthesis of nicotine is an intermediate in the synthesis of tropane alkaloid derived. Biosynthesis begins with the decarboxylation of ornithine decarboxylase by ornithine (ODC) to produce putrescine. Then converted into putrescine N-methyl putrescine through methylation by SAM catalyzed by putrescine N-methyltransferase (PMT). N-methylputrescine then undergoes deamination to 4-methylaminobutanal by N-methylputrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize to N-methyl-Δ1-pyrrollidium cations.

The final step in the synthesis of nicotine is the coupling between the N-methyl-Δ1-pyrrollidium cation and nicotinic acid. Although studies suggest that some forms the link between the two components of the structure, processes and mechanisms that would still not been determined. The theory agreed today involving the conversion of nicotinic acid to 2,5-dihydropyridine with 3.6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate then reacts with the N-methyl-Δ1-pyrrollidium cations to form enantiomerically pure (-)-nicotine.