Nicotine synthase

Friesen, J.B. and Leete, E. (1990) Nicotine synthase an enzyme from Nicotiana species which catalyses the formation of (S)-nicotine from nicotinic acid and 1-methyl-A -pyrrolinium chloride. Tetrahedron Lett., 31, 6295-8. 

Mannucd C, Catania MA, Adamo EB, BeUomo M, Caputi AP, Calapai G (2005) Long term effects of high doses of nicotine on feeding behavior and brain nitric oxide synthase activity in female mice. J Pharmacol Sci 98 232-238... 

In 1989, BH4 was found to be a cofactor for nitric oxide synthase (NOS) [ 126, 127]. BH4 is also involved in dimerization of NOS, as NOS is catalytically active in a homodimer structure. Three isoforms of NOS exist neuronal NOS (NOS 1), inducible NOS (NOS 2) and endothelial NOS (NOS 3). BH4 is essential for all NOS isoforms. The NOS isoforms share approximately 50-60% sequence homology. Each NOS polypeptide is comprised of oxygenase and reductase domains. An N-terminal oxygenase domain contains iron protoporphyrin IX (heme), BH4 and an arginine binding site, and a C-terminal reductase domain contains flavin mononucleotide (FMN), and a reduced nicotin-amide adenine dinucleotide phosphate (NADPH) binding site. 

The first committed step in TA and nicotine biosynthesis is catalyzed by putrescine JV-methyltransferase (PMT) (Fig.7.4).82 A PMT cDNA isolated from tobacco showed extensive homology to spermidine synthase from mammalian and bacterial sources.83 A-Methylputrescine is oxidatively deaminated to 4-aminobutanal, which undergoes spontaneous cyclization to form the reactive A-methyl-A1-pyrrolinium cation. Although the enzymes involved are unknown, the A-methyl-A1-pyrrolinium cation is thought to condense either with acetoacetic acid to yield hygrine as a precursor to the tropane ring, or with nicotinic acid to form nicotine. 

Two enz)mies of pyrrolidine alkaloid formation responsible for the conversion of putrescine to the N-methylpyrrolinium ion have been investigated in some detail. PMT, partially purified from cultures of Hyoscyamus niger and fully characterized from Datura stramonium, has been cloned by differential screening of complementary deoxyribonucleic acid (cDNA) libraries from high- and low-nicotine-yielding N. tabacum plants (Hibi et ah, 1994). The enzyme shows considerable sequence homology to spermidine synthase but is distinct from this enz)mie as it only shows PMT activity when expressed in Escherichia coli. MPO has been isolated in pure form from N. tabacum transformed root cultures (McLauchlan et ah, 1993). It is quite widely spread in... 

Vitamin B12 and folate are both required for conversion of homocysteine to methionine. Increased serum homocysteine may help define vitamin B12 or folate deficiency. Homocysteine levels can also be elevated in vitamin Bg deficiency, renal failure, hypothyroidism, and in persons with a genetic defect in cystathionine /S-synthase. Additionally, elevated levels have been caused by medications including nicotinic acid, theophylline, methotrexate, and L-dopa. 

Activity of NAPRT was increased in P. falciparum-infected red blood cells as was nicotinamide synthase and nicotinamide deamidase NAAD and NAD phosphorylase remained at similar levels upon infection. It was concluded that the majority of NAD synthesis in P. falciparum occurs from both nicotinic acid and nicotinamide via nicotinamide deamidase, NAPRT, NAAD phosphorylase and NAD synthase (Zerez et ah, 1990). None of the genes for these enzymes has been cloned neither have the enzymes been isolated. However, evidence for them can be found in the P. falciparum genome database (http //www.plasmodb.org last accessed 16 July 2008). 

Figure 31 The structure and mechanism of a-ribazole synthesis, (a) The structure of the anaerobic pathway a-ribazoie synthase, CobT, is shown. The two subunits of the homodimeric enzyme are differentiaiiy coiored (green heiices/yeiiow sheets and biue helices/purple sheets). The active site is marked by the binding of the a-ribazoie (stick representation), (b) The mechanism involves the attachment of DMB to the ribose moiety of NaMN, generating a-ribazole and nicotinic acid.

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