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MetaCyc Pathway: trigonelline biosynthesis
Inferred from experimentAuthor statementTraceable author statement to experimental support

Enzyme View:

Pathway diagram: trigonelline biosynthesis

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisSecondary Metabolites BiosynthesisNitrogen-Containing Secondary Compounds BiosynthesisAlkaloids BiosynthesisPyrrolidine, Piperidine and Pyridine Alkaloids Biosynthesis
BiosynthesisSecondary Metabolites BiosynthesisNitrogen-Containing Secondary Compounds BiosynthesisNon protein Amino Acids Biosynthesis

Some taxa known to possess this pathway include : Glycine max, Pisum sativum

Expected Taxonomic Range: Magnoliophyta

General Background

Trigonelline, the N-methyl conjugate of nicotinic acid was first isolated from seeds of fenugreek (Trigonella foenum-graecum) [Jahns85] and has been found since in many other plant species including pea, hemp, coffee, soybean and potatoes [Fodor85]. Trigonelline is often classified as a pyridine alkaloid [Dewick97] [Seigler98]. As a direct derivative of nicotinic acid trigonelline belongs to the so-called 'pseudoalkaloids' which may be the reason that other authors do not list this compound as an alkaloid but rank it more generic among nitrogen containing compounds [Harborne93].

Trigonelline is regarded as a physiological active compound in plants inducing leaf movements [Ueda00], accumulating upon stress [Cho99b] and acting as an osmoprotectant [Rajasekraran01]. Moreover, trigonelline has been found to function as a hormone that is involved in the control of the cell cycle in plants and animals. It was established that trigonelline was capable of promoting specific G2 cellular arrest [Tramontano82]. The molecular reason for that seems to be a specific interference of trigonelline with the DNA replication process causing an elongated cell cycle and impair root elongation [Mazzuca00]. The G2 cellular arrest caused by trigonelline was found to depend on the age of the organism. Older seedlings of Pisum sativum produce an unusual substituted pyrrole that has been identified as an endogenous control factor that could override trigonelline induced cellular arrest [Lynn87].

About This Pathway

The biosynthesis of trigonelline has been investigated in connection with nicotinic acid (niacin) biosynthesis and NAD recycling in plants (similar to NAD salvage pathway I and pyridine nucleotide cycling (plants)) [Arditti79] [Zheng04a]. The N-methylation of nicotinic acid forming trigonelline is catalyzed by the nicotinate N-methyltransferase (EC which has been first investigated in seeds of Pisum sativum [Joshi60]. This enzyme was later purified and characterized demonstrating a high preference for nicotinic acid as substrate but not for nicotinamide which has been often observed with partially purified enzymes [Upmeier88].

Trigonelline has long been considered as a metabolic dead-end product but continuous research revealed that this nicotinic acid conjugate rather constitutes a kind of a storage form of niacin which can be re-converted to nicotinic acid, hence feeding the pyridine nucleotide cycle [Joshi62] [Taguchi83]. The conversion back to nicotinic acid is due to a demethylating activity which is predominantly non-oxidative [Heeger76] but the responsible enzyme and the methyl group acceptor remains to be characterized. However, the relatively slow demethylation of trigonelline to nicotinate has caused doubt on the notion of trigonelline being a true storage compound [Upmeier88a]. Instead, it was proposed that the formation of trigonelline may rather represent the detoxification of excess nicotinate and nicotinamide released from the pyridine nucleotide cycle [Zheng05b].

Created 14-Feb-2006 by Foerster H, TAIR


Arditti79: Arditti J, Tarr JB (1979). "Niacin biosynthesis in plants." Amer J Bot, 66(9), 1105-1113.

Cho99b: Cho Y, Lightfoot DA, Wood AJ (1999). "Trigonelline concentrations in salt stressed leaves of cultivated Glycine max." Phytochemistry, 52, 1235-1238.

Dewick97: Dewick PM (1997). "Medicinal natural products. A biosynthetic approach." John Wiley & Sons, Chichester New York Weinheim Brisbane Singapore Toronto.

Fodor85: Fodor GB, Colasanti B (1985). "The pyridine and piperidine alkaloids: Chemistry and pharmacology." In: Alkaloids: Chemical and biological perspectives. Vol 3. (Pelletier SW ed.), 1-90, Wiley, New York.

Harborne93: Harborne JB, Baxter H (1993). "Phytochemical Dictionary. A handbook of bioactive compounds from plants." Taylor & Francis, London Washington, DC.

Heeger76: Heeger V, Leienbach KW, Barz W (1976). "[Metabolism of nicotinic acid in plant cell suspension cultures, III: Formation and metabolism of trigonelline (author's transl)]." Hoppe Seylers Z Physiol Chem 357(8);1081-7. PMID: 185134

Jahns85: Jahns E (1885). "Ueber die Alkaloide des Bockshornsamens." Ber Deut Chem Ges, 18, 2518-2523.

Joshi60: Joshi JG, Handler P (1960). "Biosynthesis of trigonelline." J Biol Chem 235;2981-3. PMID: 13790768

Joshi62: Joshi JG, Handler P (1962). "Metabolism of trigonelline." J Biol Chem 237;3185-8. PMID: 14029718

Lynn87: Lynn DG, Jaffe K, Cornwall M, Tramontano WA (1987). "Characterization of an Endogenous Factor Controlling the Cell Cycle of Complex Tissues." J. Am. Chem. Soc., 109, 5859-5861.

Mazzuca00: Mazzuca S, Bitonti MB, Innocenti AM, Francis D (2000). "Inactivation of DNA replication origins by the cell cycle regulator, trigonelline, in root meristems of Lactuca sativa." Planta 211(1);127-32. PMID: 10923713

Rajasekraran01: Rajasekraran LR, Aspinall D, Jones GP, Paleg LG (2001). "Stress metabolism. IX. Effect of salt stress on trigonelline accumulation in tomato." Can J Plant Sci, 81, 487-498.

Seigler98: Seigler DS (1998). "Plant secondary metabolism." Kluwer Academic Publishers, Boston Dordrecht London.

Taguchi83: Taguchi H, Shimabayashi Y (1983). "Findings of trigonelline demethylating enzyme activity in various organisms and some properties of the enzyme from hog liver." Biochem Biophys Res Commun 113(2);569-74. PMID: 6347195

Tramontano82: Tramontano WA, Hartnett CM, Lynn DG, Evans LS (1982). "Relationship between trigonelline concentration and promotion of cell arrest in g2 in cultured roots of Pisum sativum." Phytochemistry, 21(6), 1201-1206.

Ueda00: Ueda M, Yamamura S (2000). "Chemistry and Biology of Plant Leaf Movements." Angew Chem Int Ed Engl 39(8);1400-1414. PMID: 10777626

Upmeier88: Upmeier B, Gross W, Koster S, Barz W (1988). "Purification and properties of S-adenosyl-L-methionine:nicotinic acid-N-methyltransferase from cell suspension cultures of Glycine max L." Arch Biochem Biophys 262(2);445-54. PMID: 3364975

Upmeier88a: Upmeier B, Thomzik JE, Barz W (1988). "Nicotinic acid-N-glucoside in heterotrophic parsley cell suspension cultures." Phytochemistry, 27(11), 3489-3493.

Zheng04a: Zheng XQ, Nagai C, Ashihara H (2004). "Pyridine nucleotide cycle and trigonelline (N-methylnicotinic acid) synthesis in developing leaves and fruits of Coffea arabica." Physiologia Plantarum, 122, 404-411.

Zheng05b: Zheng XQ, Hayashibe E, Ashihara H (2005). "Changes in trigonelline (N-methylnicotinic acid) content and nicotinic acid metabolism during germination of mungbean (Phaseolus aureus) seeds." J Exp Bot 56(416);1615-23. PMID: 15837705

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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