Tenuazonic acid

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Structural formula
L-tenuazonic acid
L- tenuazonic acid
General
Surname Tenuazonic acid
other names

(2 S ) -4-Acetyl-2 - [(2 S ) -butan-2-yl] -5-hydroxy-1,2-dihydropyrrol-3-one

Molecular formula C 10 H 15 NO 3
External identifiers / databases
CAS number 610-88-8
EC number 636-400-2
ECHA InfoCard 100.164.201
PubChem 54683011
Wikidata Q286126
properties
Molar mass 197.23 g mol −1
safety instructions
GHS labeling of hazardous substances

The information relates to the copper salt.

06 - Toxic or very toxic

danger

H and P phrases H: 301
P: 301 + 310
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Tenuazonic acid is a mold toxin ( mycotoxin ), which is mainly formed by molds of the genus Alternaria . Tenuazonic acid is thus a representative from the group of substances tetramic - derivatives .

The systematic chemical name for the chiral molecule is (2 S ) -4-acetyl-2 - [(2 S ) -butan-2-yl] -5-hydroxy-1,2-dihydropyrrol-3-one, but is often also L- tenuazonic acid or the abbreviation L -TA used.

history

Tenuazonic acid was first isolated in 1958 from an extract of an Alternaria alternata culture (in older literature: Alternaria tenuis ). The elucidation of the molecular structure followed a year later.

Occurrence

Tenuazonic acid is mainly produced by molds of the genus Alternaria . However, Piricularia orycae and Phoma sorghina also produce this mycotoxin .

biosynthesis

Experiments with 14 C-labeled acetate have shown that tenuazonic acid is biosynthesized in Alternaria alternata from one molecule of L - isoleucine and two molecules of acetate.

Biological significance and toxicity

Tenuazonic acid has cytotoxic, antibacterial, antiviral and phytotoxic properties. According to in-vivo and in-vitro studies, the biological activity of tenuazonic acid is due to the inhibition of protein biosynthesis, whereby the release of newly formed proteins from the ribosomes is suppressed and the incorporation of new amino acids into proteins is prevented.

In plants, the inhibition of protein and nucleic acid biosynthesis leads to leaf rot and brown spot disease. In young chickens, oral administration of 1.25 mg tenuazonic acid per kilogram body weight over a period of 3 weeks resulted in significant organ damage. The oral LD 50 in mice is 225 mg / kg; with intravenous administration values ​​of 125 mg / kg (mice) and> 50 mg / kg (monkeys) were determined.

Occurrence in food

Because of the widespread occurrence of Alternaria spp. On plants used for food production , the mycotoxin tenuazonic acid formed by this mold of the class Dothideomycetes ( hose fungus ) can often be detected in various foods. The following list gives an overview of the foods in which tenuazonic acid has already been detected:

Food Medium tenuazonic acid content
Grain 1000–8000 µg kg −1
Cereal products 50 µg kg −1
beer 11 µg kg −1
Tomato products 50–60 µg kg −1

Only very low levels of tenuazonic acid were found in baby food. Products based on millet, which were very heavily contaminated with tenuazonic acid (130 - 1200 µg / kg), are an exception. The causes of this contamination and the relevance for the health of the consumer cannot be assessed at the moment due to the unclear data situation on the toxicology of tenuazonic acid.

Limit values

The legislature has not yet issued any limit values ​​for tenuazonic acid.

Analytics

Tenuazonic acid can be analyzed using chromatographic methods such as thin layer chromatography (TLC), gas chromatography (GC) and high-performance liquid chromatography (HPLC), the latter analysis technique being highly preferred. However, the HPLC analysis of tenuazonic acid is in principle limited by the fact that tenuazonic acid has very poor chromatographic properties due to its strongly acidic and complex-forming properties. This can be compensated for by adding zinc sulfate or other modifying additives to the mobile phase. Since these additives are not suitable when using a mass spectrometer as a detector ( LC-MS ), the derivatisation of tenuazonic acid as 2,4-dinitrophenylhydrazone is recommended in these cases . This derivatization enables a safe and precise determination of tenuazonic acid in food by means of HPLC coupled with tandem mass spectroscopy (LC-MS / MS). Matrix-dependent variations in the derivatization or ionization in the ion source of the mass spectrometer can be best achieved by using a stable isotope-labeled internal standards as part of a stable isotope dilution assay are compensated (SIVA). For tenuazonic acid, this was done using [ 13 C 6 , 15 N] -tenuazonic acid.

A promising approach for the direct LC-MS / MS analysis of tenuazonic acid without derivatization works with the addition of ammonium hydrogen carbonate to the mobile phase (pH 7.5), a suitable stationary phase, [ 13 C 2 ] -labeled tenuazonic acid as internal Standard and using the QuEChERS methodology for sample preparation.

Tenuazonic acid can also be analyzed by immunochemical detection techniques. An enzyme-linked immunosorbent assay (ELISA) was developed for apple and tomato products .

In samples that were very highly contaminated with tenuazonic acid, in addition to tenuazonic acid itself, related compounds derived from the amino acids valine and leucine could be detected.

literature

  • Weidenbörner, M .: Lexicon of food mycology. Springer-Verlag, 1999

Individual evidence

  1. ↑ a b Data sheet Tenuazonic acid copper salt from Alternaria alternata from Sigma-Aldrich , accessed on December 28, 2011 ( PDF ).
  2. ↑ a b c Entry on tenuazonic acid in the ChemIDplus database of the United States National Library of Medicine (NLM)
  3. ↑ a b c CRC Handbook of Antibiotic Compounds, Vol. 1, Berdy, J., Boca Raton, FL, CRC Press, 1980, Vol. 5, p. 65, 1981.
  4. ↑ a b c Entry on tenuazonic acid. In: Römpp Online . Georg Thieme Verlag, accessed on November 11, 2013.
  5. ↑ Rosett, T. et al .; Biochem J . ; 67, pp. 390-400 (1957).
  6. ↑ CE Stickings: Studies in the biochemistry of micro-organisms. 106. Metabolites of Alternaria tenuis auct .: the structure of tenuazonic acid. In: The Biochemical journal. Volume 72, Number 2, June 1959, pp. 332-340, PMID 13662306 , PMC 1196930 (free full text).
  7. ↑ Bottalico, A., Logrieco, A .; In: Mycotoxins in Agriculture and Food Safety; Marcel Dekker, Inc .: New York, NY, 1998, pp. 65-108.
  8. ↑ Umetsu, N. et al .; Agr Biol Chem ; 38: 1867-1874 (1974).
  9. ↑ Umetsu, N. et al .; Agr Biol Chem ; 1972, 36: 859-866.
  10. ↑ Steyn, PS, Rabiet, CJ; Phytochemistry 15 (1976), pp. 1977-1979.
  11. ↑ Stickings, CE; Townsend, RJ; Biochem J .; 78, pp. 412-418 (1961).
  12. ^ Lattice man, CO; J. Med. Chem. 8 (1965), pp. 483-486.
  13. ↑ Miller, FA et al .; Nature , 200, pp. 1338-1339 (1963).
  14. ↑ Lebrun, MH et al .; Phytochemistry , 27: 77-84 (1988).
  15. ↑ Shigeura, HT, Gordon, CN; Biochemistry , 2, pp. 1132-1137 (1963).
  16. ↑ Azcarate, MP et al. J. Food Prot. 71 (2008), pp. 1262-1265
  17. ↑ Li, FQ and Yoshizawa, T .; J. Agric. Food Chem. 48 (2000), pp. 2920-2924.
  18. ↑ a b Siegel, D. et al .; J Chromatogr A 1216 (2009), pp. 4582-4588.
  19. ^ Siegel, D. et al .; Food Chem . 120 (2010), pp. 902-906
  20. ↑ a b Asam, S. et al .; J. Agric. Food Chem. 59 (2011), pp. 2980-2987.
  21. ↑ Asam, S. et al .; Eur. Food Res. Technol. 236 (2013), pp. 491-497.
  22. ↑ a b Scott, PM; JAOAC Int. 84 (2001), pp. 1809-1817.
  23. ↑ Lohrey, L. et al .; J. Agric. Food Chem. 61 (2013), pp. 114-120.
  24. ↑ Groß, M. et al .; J. Agric. Food Chem. 59 (2011), pp. 12317-12322.
  25. ↑ Asam, S. et al .; J. Chromatogr. A 1289 (2013), pp. 27-36.