Nicotine catabolism

Schenk S, A Hoelz, B Krauss, K Decker (1998) Gene structures and properties of enzymes of the plasmid-encoded nicotine catabolism of Arthrobacter nicotinovorans. J Mol Biol 284 1323-1339. 

Chiribau CB, C Sandu, M Eraaije, E Schiltz, R Bradsch (2004) A novel y-A-methylaminohutyrate demethyl-ating oxidase involved in catabolism of the tobacco alkaloid nicotine by Arthrobacter nicotinovorans pAOl. Eur JBiochem 271 4677-4684. 

Niacin (nicotinic acid) reduces the hepatic synthesis of VLDL, which in turn leads to a reduction in the synthesis of LDL. Niacin also increases HDL by reducing its catabolism. 

Niacin ia a nutritional term applied to both nicotinic acid and nicotinamide and to a mixture of the two. Their structures and those of their coenzymes are given in Table 6.1. Numerous redox reactions use NAD+ and NADP+ or NADH and NADPH. The latter are used largely in reactions designed to reductively synthesize various substances, mostly in the extramitochondrial areas of the cell. NAD+, on the other hand, is used largely in its oxidized form in catabolic redox reactions. The rat liver cytosol NADPH/NADP+ ratio is about 80, whereas its NADH/NAD+ ratio is only 8 x 10 4. Table 6.3 lists some biochemical reactions in which these cofactors participate. It shows that they are of crucial importance in the metabolism of carbohydrates, fats, and amino acids. 

As mentioned earlier, milk was often used to treat pellagra however, neither milk nor eggs contain very much niacin. The question arises How can milk reverse the symptoms of a disease known to result mainly from niacin deficiency The answer lies in a consideration of the pathway of catabolism of one of the amino acids, tryptophan. The breakdown of tryptophan may follow a number of different routes, including that shown in Figure 9.68. The final pniduct of this pathway is nicotinic acid ribonucleotide, which can be converted to NAD. A small fraction of... 

This overview will consider some of the advantages and limitations of using immunochemical techniques to identify and quantify environmentally important agents. A few illustrative examples will be taken from methods used to quantify nicotine and its metabolites. We are interested in nicotine because it is pharmacologically active and the agent responsible for addiction to tobacco products. Once, also, it was used widely as a pesticide. Its catabolism in mammals is complex some of the more common metabolites are shown in Figure 1 11,12). 

Figure 9 Catabolic pathway of nicotinic acid (68) (niacin, vitamin B3).

Tryptophan - (Figure 21.22) - Tryptophan is catabolized to either glutaryl-CoA and acetoacetyl-CoA (major route) or NAD+. NAD+ can also be made from nicotinic acid (Table 11.5). 

Tryptophan is among the most interesting aminoacids because its biologic role goes far beyond its participation in proteins structure. In mammals, tryptophan is the precursor in the synthesis of the neurotransmitters tryp-tamine and serotonine, as well as of other bioactive molecules such as kynurenic and quinolinic acids. Along with the usual catabolic pathway of the aminoacid, other essential compounds are found, such as nicotinic acid and melatonin [1-3]. 

Although the specificity of receptors is not so strict as that of the most important anabolic and catabolic enzymes, it is at least as strict as the degrad-ative enzymes of microsomes (see Section 3.5). Thus at ganglia, nicotine (but not muscarine) can take the place of acetylcholine, whereas at postganglionic parasympathetic synapses, muscarine (but not nicotine) can take its place (see Table 7.1). Further specificity is shown in acetylcholine antagonism, for which tubocurarine is specific at the neuromuscular junction, hexamethonium at ganglia, and atropine at parasympathetic postganglionic synapses. 

Plants produce various pyridine alkaloids derived from nicotinic acid. Trigonelline, the major component in coffee seeds, and ricinine, the toxic alkaloid produced by Ricinus communis, are formed from nicotinic acid originating from the NAD catabolism [20, 25, 26], Quinolinic acid was found to be an efficient precursor in the biosynthesis of nicotine [27]. 

The data indicate that hydroxykynureninase, an enzyme with high preference for hydroxykvTiurenine as substrate when compared with kynurenine, is involved in the synthesis of 3-hydroxyamhranilic acid (3-HA). 3-HA is well known as an intermediate in the catabolism of tryptophan, and in eukaryotes it serves as precursor of nicotinic acid... 

Thus, in the cell, the newly synthesized NAD is faced with several foes, and the cell must either provide NAD at a rate more rapid than that at which the coenzyme is hydrolyzed, or the new NAD must be kept separate from the catabolic enzymes. The intracellular distribution of the enzymes involved in NAD metabolism, therefore, is of capital interest. The enzyme that catalyzes the formation of deamido NAD from ATP and nicotinic acid mononucleotide is in the nucleus, as was first shown by Hogeboom and Schneider [93]. Later, Elyane Baltus also demonstrated that, at least in the starfish, this reaction is restricted to the nucleolus [94]. 

Among the most interesting of the biological reactions of tryptophan is its conversion to nicotinic acid. In the vertebrates, at any rate, this is a truly anabolic process which serves the end of providing source material for the synthesis of DPN and TPN. The discussion of this pathway of metabolism is contained in the chapter. Synthetic Processes Involving Amino Acids. Conversion to nicotinic acid can not be the major pathway for the catabolism of tryptophan. Based on the capacity of fed tryptophan to prevent symptoms of niacin deficiency in animals, it can be calculated that only 1% or 2% is thus converted in man and the primates. In the rat the conversion may amount to as much as 10%. 

Literature about the extensive degradation of nicotine is richer than that on the catabolism of any other alkaloid. In spite of that, it is not yet possible to give a clear-cut and concise review of definite, established pathways. 

Thus gramine becomes the second example of an alkaloid (after nicotine) that is transformed into an amino acid through catabolic reactions in the plant that produces it. 

As shown in Figure 11.13, the nicotinamide nucleotide coenzymes can be synthesized from either of the niacin vitamers, and from quinolinic acid, an intermediate in the metabolism of tryptophan. In the liver, the oxidation of tryptophan results in a considerably greater synthesis of NAD than is required, and this is catabolized to release nicotinic acid and nicotinamide, which are taken up and used by other tissues for synthesis of the coenzymes. 

Figure 2 NAD metabolism. Tip = tryptophan, 3-HK = 3-hydroxykynurenine, 3-HA = 3-hydroxyanthranilic acid, ACMS = a-amino-P-carboxymuconate- -semialdehyde, AMS = a-aminomuconate- -semialdehyde, NaMN = nicotinic acid mononucleotide, NMN = nicotinamide mononucleotide, NaAD = nicotinic acid adenine dinucleotide. For other abbreviations, see Figure 1. (1) tryptophan oxygenase [EC 1.13.11.11], (2) formy-dase [EC 3.5.1.9], (3) kynurenine 3-hydroxylase [EC 1.14.13.9], (4) kynureninase [EC 3.7.1.3], (5) 3-hydroxyanthranilic acid oxygenase [EC 1.13.11.6], (6) nonenzymatic, (7) aminocarboxymuconate-semialdehyde decarboxylase [EC 4.1.1.45], (8) quinolinate phos-phoribosyltransferase [EC 2.4.2.19], (9) NaMN adenylyltransferase [EC 2.7.2.18], (10) NAD synthetase [EC 6.3.5.1], (11) NAD kinase [EC 2.7.1.23], (12) NAD" glycohydro-lase [EC 3.2.2.5], (13) nicotinamide methyltransferase [EC 2.2.1.1], (14) 2-Py-forming MNA oxidase [EC 1.2.3.1], (15) 4-Py-forming MNA oxidase [EC number not given], (16) nicotinamide phosphoribosyltransferase [EC 2.4.2.12], (17) NMN adenylytransferase [EC 2.7.71], (18) nicotinate phosphoribosyltransferase [EC 2.4.2.11], (19) nicotinate methyltransferase [EC 2.7.1.7], and nicotinamidase [EC 3.5.1.19]. Solid line, biosynthesis dotted line, catabolism.

Table 5 Daily Urinary Excretion of Nicotinic Acid and Nicotinamide and Their Catabolic Metabolites... 

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