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Metabolic Fate of Nicotinamide in Higher Plants

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Metabolic Fate of Nicotinamide in Higher Plants Physiologia Plantarum 131: 191–200. 2007 Copyright ª Physiologia Plantarum 2007, ISSN 0031-9317 Metabolic fate of nicotinamide in higher plants Ayu Matsuia, Yuling Yina, Keiko Yamanakab, Midori Iwasakib and Hiroshi Ashiharaa,b,* aDepartment of Biological Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Bunkyo-ku, Tokyo 112-8610, Japan bDepartment of Biology, Faculty of Science, Ochanomizu University, Bunkyo-ku, Tokyo 112-8610, Japan Correspondence Metabolism of [carbonyl-14C]nicotinamide was surveyed in various plant *Corresponding author, materials including the model plants, Arabidopsis thaliana, Oryza sativa and e-mail: [email protected] Lotus japonicus. In all plants studied, nicotinamide was used for the pyridine (nicotinamide adenine) nucleotide synthesis, probably after conversion to Received 6 May 2007; revised 9 June 2007 nicotinic acid. Radioactivity from [carbonyl-14C]nicotinamide was incorpo- doi: 10.1111/j.1399-3054.2007.00959.x rated into trigonelline (1-N-methylnicotinic acid) and/or into nicotinic acid 1N-glucoside (Na-Glc). Trigonelline is formed mainly in leaves and cell cultures of O. sativa and L. japonicus and in seedlings of Trifolium incarnatum, Medicago sativa and Raphanus sativus. Trigonelline synthesis from nicotinamide is generally greater in leaves than in roots. Na-Glc was formed as the major nicotinic acid conjugate in A. thaliana and in tobacco Bright Yellow-2 cells. In seedlings of Chrysanthemum coronarium and Theobroma cacao, both trigonelline and Na-Glc were synthesized from [carbonyl-14C]nicotinamide. Trigonelline is accumulated in some seeds, mainly Leguminosae species. The pattern of formation of the nicotinic acid conjugates differs between species and organs. Introduction acid as diet is salvaged by nicotinate phosphoribosyltrans- Nicotinamide is formed as a catabolite of nicotinamide ferase (EC 2.4.2.11) to NaMN and is used in NAD synthesis adenine nucleotide and is a key metabolite of pyridine (Brenner 2005, Revollo et al. 2004, Sestini et al. 2000). metabolism. It is similar to purine and pyrimidine bases Plants lack nicotinamide phosphoribosyltransferase, so (Ashihara and Crozier 1999, Moffatt and Ashihara 2002, that the pathway via NaMN is functional; nicotinamide is Stasolla et al. 2003, Zrenner et al. 2006); this pyridine base converted to nicotinic acid, which is then phosphoribosy- is salvaged to nicotinamide mononucleotide (NMN) or lated in plants (Ashihara et al. 2005, Zheng et al. 2005). nicotinic acid mononucleotide (NaMN) and is used for Outlines of the metabolic pathways are shown in Fig. 1. regeneration of NAD and NADP (Ashihara et al. 2005). Less In addition to salvage, nicotinamide and nicotinic acid is known about pyridine metabolism in plants (Katoh and are used in a few plants for the synthesis of alkaloids such Hashimoto 2004, Noctor et al. 2006) than in mammals or as nicotine (Katoh and Hashimoto 2004) and ricinine microorganisms (Moat and Foster 1987). Some differences (Waller et al. 1966), in very limited plants, such as between plants and animals are known. In mammals, tobacco and castor bean plants for instance. A simple nicotinamide is salvaged to NMN directly by nicotinamide and ubiquitous alkaloid is derived from nicotinic acid phosphoribosyltransferase (EC 2.4.2.12) or by two-step in the one-step conversion to trigonelline (1-N-methyl- reactions via nicotinamide riboside (NR) (Magni et al. nicotinic acid) by an N-methyltransferase. In the 1980s, 1999). Although nicotinamide is not deaminated to Tramontano et al. (1983) and Barz (1985) published nicotinic acid in mammals, exogenously supplied nicotinic reports on trigonelline formation and its possible functions, Abbreviations – NaAD, nicotinic acid adenine dinucleotide; Na-Glc, nicotinic acid 1N-glucoside; NaMN, nicotinic acid mononucleotide; NaR, nicotinic acid riboside; NMN, nicotinamide mononucleotide; NR, nicotinamide riboside; PNC, pyridine nucleotide cycle. Physiol. Plant. 131, 2007 191 COOH CONH2 COOH + + + N Adenine N Adenine N (3) (4) Ribose Ribose Ribose Ribose Ribose P P P P PPi ATP AMP+PPi P ATP NaAD Gln Glu NAD NaMN (2b) ADP ATP (5) COOH PPi ADP-ribose (2) + NaR N (5a) AMP PRPP Pi SAH CONH2 CH3 SAM Trigonelline R1P (2a) + Pi N CONH Ribose (A) COOH 2 (7) (6) (1) Ribose NR N N UDPG P UDP NH3 Nicotinic acid Nicotinamide NMN (B) COOH + N Glucose CONH2 Na-glucoside + N CH3 1-methylnicotinamide Fig. 1. Metabolic fate of nicotinamide in plants. PNC and synthesis of nicotinic acid conjugates are shown. A seven-member PNCVII (reactions 1–7), eight-member PNC VIII (reactions 1, 2a, 2b and 3–7) and five-member PNC V (reactions 1–4 and 5a) may be operative in plant cells. Other cycles, such as that including NR deaminase, are also possible. Trigonelline (reaction A) and Na-Glc (reaction B) are synthesised from nicotinic acid. PRPP, 5- phosphoribosyl pyrophosphate; RIP, ribose-1-phosphate; SAH, s-adenosyl-homocystein; SAM, s-adenosyl-methronine. but their work has not been followed up nicotinamide is been partially sequenced. The tobacco (Nicotiana tabacum) converted to 1N-methylnicotinamide in some organisms Bright Yellow (BY)-2 cell line is often used in plant (Shibata et al. 1996), but no such reaction has been physiological studies at the cellular level (Nagata et al. 1992). reported in plants. In some plant species, nicotinic acid To understand the function of metabolic pathways in 1N-glucoside (Na-Glc) is formed (Upmeier et al. 1988c). relation to physiological phenomena such as environment This compound has been incorrectly reported as nicotinic stress and growth stages of plants, databases on genome acid arabinoside (Willeke et al. 1979), but it was corrected (DNA), transcriptome (mRNA), proteome (enzyme) and as Na-Glc by the same group (Barz 1985, Upmeier et al. metabolome (metabolite) information are useful. If basic 1988c). Diversity of trigonelline and Na-Glc in plant cell information on in situ metabolism is provided, such cultures has been reported (Willeke et al. 1979). databases can be used more properly. This study seeks to Recently, some model plants have been used for determine the metabolic fate of 14C-labelled nicotinamide metabolic studies of higher plants at molecular and/or in cells and tissues of various plants, including model plants. cellular level. Arabidopsis thaliana is the most popular In addition to the model plants specified above, we dicot model plant for which the genome has been fully examined the metabolic fate of [14C]nicotinamide in sequenced. Rice (Oryza sativa) is used as a monocot each organ of cacao seedlings. We also investigated model plant and has one of the smallest genomes of trigonelline accumulation in various seeds and compared cereal species. Lotus japonicus is a legume model and is the metabolism of nicotinamide in seedlings of plants that useful for studies of symbiosis and nitrogen fixation (Sato store a high concentration of trigonelline in seeds (clover and Tabata 2006, Udvardi et al. 2005); its genome has and alfalfa) and in plants that lack trigonelline in seeds 192 Physiol. Plant. 131, 2007 (chrysanthemum and radish). Our results suggest that (22°C). After incubation, the glass tube was removed from nicotinamide salvage for NAD synthesis is generally the centre well and placed in a 50-ml Erlenmeyer flask active in actively growing cells of all plant species exam- containing 10 ml of distilled water. Samples were collected ined, but synthesis of trigonelline is absent in some plant by filtering through a tea strainer or a layer of Miracloth species. Trigonelline synthesis was extremely high in leaves (Merck, Darmstadt, Germany) on a Bu¨chner funnel, were of rice, L. japonicus, cacao and radish, but no or little washed with distilled water, then frozen with liquid biosynthetic activity was detected in A. thaliana or cul- nitrogen and stored at 280°C until extraction. Potassium tured tobacco BY-2 cells. In contrast to trigonelline synthesis, bicarbonate that had been absorbed by the filter paper was Na-Glc formation was found in only a few plant species. allowed to diffuse into 10 ml distilled water overnight, and aliquots of the resulting solution (usually 0.5 ml) were used for the determination of radioactivity. Radioactivity was Materials and methods measured with a liquid scintillation analyser (Beckman, type LS 6500, Beckman Instruments, Fullerton, CA). Plant materials The labelled metabolites were extracted with 80% Lotus japonicus seeds were obtained from the National methanol (v/v) containing 20 mM sodium diethyldithio- Bioresource Project (L. japonicus and Glycine max) Core carbamate and were analysed as described previously Facility Office, Department of Agriculture, Miyazaki (Zheng and Ashihara 2004). Plant materials were homo- University, Miyazaki, Japan. Seeds of Picea glauca were genized in a mortar and pestle with the extraction supplied by Professor E. C. Yeung, Department of medium, and the resulting methanol-soluble fraction Biological Sciences, University of Calgary, Canada. Seeds was evaporated in vacuo to dryness at 37°C. of rice (O. sativa cv. Nihonbare) were donated by The labelled metabolites were separated by TLC using Professor N. Yamamoto of our Department. Cacao seeds microcrystalline cellulose TLC plates (Merck, Darmstadt, were supplied by Dr C. Nagai, Hawaii Agriculture Germany). Solvent systems I and IV of our previous paper Research Center, USA. Other seeds were purchased from (Zheng and Ashihara 2004) were used to identify the Carolina Biological Supply Company, Burlington, NC, radiolabelled metabolites. Radioactivity on the TLC sheet USA, or Sakata Seed Corporation, Yokohama, Japan. was determined using a Bio-Imaging Analyser (Type FLA- Seeds of A. thaliana accession Columbia and cell 2000; Fuji Photo Film Co., Ltd, Tokyo, Japan). cultures of A. thaliana, rice, L. japonicus and tobacco BY-2were obtained from the Experimental Plant Division Determination of trigonelline content of the RIKEN Bioresource Center. One-month-old Trigonelline was extracted with 80% (v/v) methanol L. japonicus plants with nodules (Oka-Kira et al. 2005) were containing 20 mM sodium diethyldithiocarbamate. After kindly supplied by Dr M. Kawaguchi, University of Tokyo.
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