Organ Location Map/System Distribution of Pungent Flavor Compounds’ Targets

2-Methylbutanoic acid (2-methylbutyric acid) is a chemical compound from the group of carboxylic acids. It occurs in two enantiomeric forms, (R)- and

(S)-2-methylbutanoic acid. (R)-2-Methylbutanoic acid occurs naturally in cocoa beans and (S)-2-methylbutanoic occurs in many fruits such as apples and

apricots.The ethyl ester is found in pineapples and oranges.

2-Methylbutanoic acid was the product of the first enantioselective synthesis in 1905 when the German chemist W. Marckwald heated ethylmethylmalonic acid

with the chiral base brucine and obtained an optically active product mixture. Both enantiomers of 2-methylbutanoic acid can be obtained by asymmetric

hydrogenation of tiglic acid using a Ru-BINAP catalyst. 2-Methylbutanoic acid is a slightly volatile, colorless liquid with an unpleasant odor that is

sparingly soluble in water.The smell differs significantly between the two forms. (S)-2-Methylbutyric acid has a pleasantly sweet, fruity odor.

(R)-2-methylbutanoic acid has a pervasive, cheesy, sweaty odor.

1. https://en.wikipedia.org/wiki/Diacetyl.

2. Zimmerman J B , Anastas P T . Toward substitution with no regrets[J]. Science, 347..

3. Pellegrino M, Steinbach N, Stensmyr M C, et al. A natural polymorphism alters odour and DEET sensitivity in an insect odorant receptor[J]. Nature, 2011, 478(7370): 511..

4. Donald S, Bronislrnv L, Andrew T. ACrylarnide is formed in the maillard reaction[J]. Nature, 2002, 419(419): 448-449..

5. Bhat S, Jones W D. An accelerated miRNA-based screen implicates Atf-3 in Drosophila odorant receptor expression[J]. Scientific reports, 2016, 6: 20109..

6. Bartowsky E J, Henschke P A. The ‘buttery’attribute of wine—diacetyl—desirability, spoilage and beyond[J]. International journal of food microbiology, 2004, 96(3): 235-252..

7. Mathews, J. M., Watson, S. L., Snyder, R. W., Burgess, J. P., Morgan, D. L. Reaction of the butter flavorant diacetyl (2, 3-butanedione) with N-α-acetylarginine: a model for epitope formation with pulmonary proteins in the etiology of obliterative bronchiolitis[J]. Journal of agricultural and food chemistry, 2010, 58(24): 12761-12768..

8. Marri, L., Jansson, A. M., Christensen, C. E., Hindsgaul, O. An enzyme-linked immunosorbent assay for the detection of diacetyl (2, 3-butanedione)[J]. Analytical biochemistry, 2017, 535: 12-18..

9. Starr, G., Petersen, M. A., Jespersen, B. M., Hansen, Å. S. Variation of volatile compounds among wheat varieties and landraces[J]. Food chemistry, 2015, 174: 527-537..

10. Kirchhoff E, Schieberle P. Quantitation of odor-active compounds in rye flour and rye sourdough using stable isotope dilution assays[J]. Journal of agricultural and food chemistry, 2002, 50(19): 5378-5385..

11. Vita, F., Taiti, C., Pompeiano, A., Gu, Z., Presti, E. L., Whitney, L., Guglielminetti, L. Aromatic and proteomic analyses corroborate the distinction between Mediterranean landraces and modern varieties of durum wheat[J]. Scientific reports, 2016, 6: 34619..

12. Farag, M. A., Song, G. C., Park, Y. S., Audrain, B., Lee, S., Ghigo, J. M., Ryu, C. M. Biological and chemical strategies for exploring inter-and intra-kingdom communication mediated via bacterial volatile signals[J]. nature protocols, 2017, 12(7): 1359..

13. Mathews, J. M., Watson, S. L., Snyder, R. W., Burgess, J. P., Morgan, D. L.. Reaction of the butter flavorant diacetyl (2, 3-butanedione) with N-α-acetylarginine: a model for epitope formation with pulmonary proteins in the etiology of obliterative bronchiolitis[J]. Journal of agricultural and food chemistry, 2010, 58(24): 12761-12768..

14. Jay J M. Antimicrobial properties of diacetyl[J]. Appl. Environ. Microbiol., 1982, 44(3): 525-532..

15. Kim K, Lee S, Ryu C M. Interspecific bacterial sensing through airborne signals modulates locomotion and drug resistance[J]. Nature communications, 2013, 4: 1809..

16. Whiteson, K. L., Meinardi, S., Lim, Y. W., Schmieder, R., Maughan, H., Quinn, R., Rohwer, F. Breath gas metabolites and bacterial metagenomes from cystic fibrosis airways indicate active pH neutral 2, 3-butanedione fermentation[J]. The ISME journal, 2014, 8(6): 1247..

17. Pham C K, Ray A. Conservation of olfactory avoidance in Drosophila species and identification of repellents for Drosophila suzukii[J]. Scientific reports, 2015, 5: 11527..

18. Turner S L, Ray A. Modification of CO 2 avoidance behaviour in Drosophila by inhibitory odorants[J]. Nature, 2009, 461(7261): 277..

19. De Bruyne M, Foster K, Carlson J R. Odor coding in the Drosophila antenna[J]. Neuron, 2001, 30(2): 537-552..

20. Weber, I. T., Johnson, L. N., Wilson, K. S., Yeates, D. G. R., Wild, D. L., Jenkins, J. A. Crystallographic studies on the activity of glycogen phosphorylase b[J]. Nature, 1978, 274(5670): 433..

21. Münch D, Galizia C G. DoOR 2.0-comprehensive mapping of Drosophila melanogaster odorant responses[J]. Scientific reports, 2016, 6: 21841..

22. Takemura, F., Iwai, K., Ikesu, M., Itoh, K., Matoike, A. Effects of inorganic anions on the photopolymerization of acrylamide sensitized by 2, 3-butanedione in aqueous solutions[J]. Polymer journal, 1988, 20(7): 565..

23. Galler, S., Höpflinger, M. C., Andruchov, O., Andruchova, O., Grassberger, H. Effects of vanadate, phosphate and 2, 3-butanedione monoxime (BDM) on skinned molluscan catch muscle[J]. Pflügers Archiv, 2005, 449(4): 372-383..

24. Herrmann, C. W. T. J., Wray, J., Travers, F., Barman, T. Effect of 2, 3-butanedione monoxime on myosin and myofibrillar ATPases. An example of an uncompetitive inhibitor[J]. Biochemistry, 1992, 31(48): 12227-12232..

25. Österman Å, Arner A, Malmqvist U. Effects of 2, 3-butanedione monoxime on activation of contraction and crossbridge kinetics in intact and chemically skinned smooth muscle fibres from guinea pig taenia coli[J]. Journal of Muscle Research & Cell Motility, 1993, 14(2): 186-194..

26. Packer, C. S., Kagan, M. L., Kagan, J. F., Robertson, S. A., Stephens, N. L. The effect of 2, 3-butanedione monoxime (BDM) on smooth muscle mechanical properties[J]. Pflügers Archiv, 1988, 412(6): 659-664..

27. Siegman, M. J., Mooers, S. U., Warren, T. B., Warshaw, D. M., Ikebe, M., Butler, T. M. Comparison of the effects of 2, 3-butanedione monoxime on force production, myosin light chain phosphorylation and chemical energy usage in intact and permeabilized smooth and skeletal muscles[J]. Journal of Muscle Research & Cell Motility, 1994, 15(4): 457-472..

28. Zhao L, Naber N, Cooke R. Muscle cross-bridges bound to actin are disordered in the presence of 2, 3-butanedione monoxime[J]. Biophysical journal, 1995, 68(5): 1980-1990..

29. Kang, C., Qiao, Y., Li, G., Baechle, K., Camelliti, P., Rentschler, S., Efimov, I. R. Human organotypic cultured cardiac slices: new platform for high throughput preclinical human trials[J]. Scientific reports, 2016, 6: 28798..

30. Sanders, L. C., Matsumura, F., Bokoch, G. M., & de Lanerolle, P. Inhibition of myosin light chain kinase by p21-activated kinase[J]. Science, 1999, 283(5410): 2083-2085..

31. Whiteson, K. L., Meinardi, S., Lim, Y. W., Schmieder, R., Maughan, H., Quinn, R., Rohwer, F.. Breath gas metabolites and bacterial metagenomes from cystic fibrosis airways indicate active pH neutral 2, 3-butanedione fermentation[J]. The ISME journal, 2014, 8(6): 1247..

32. Venkataraman, A., Rosenbaum, M. A., Werner, J. J., Winans, S. C., Angenent, L. T. Metabolite transfer with the fermentation product 2, 3-butanediol enhances virulence by Pseudomonas aeruginosa[J]. The ISME journal, 2014, 8(6): 1210..

33. Iwai, K., Matoike, A., Nishimuta, K., & Takemura, F. Micellar effects on the photopolymerization of acrylamide sensitized by 2, 3-butanedione[J]. Polymer journal, 1989, 21(5): 361..

34. Quinn, R. A., Phelan, V. V., Whiteson, K. L., Garg, N., Bailey, B. A., Lim, Y. W., Rohwer, F. L. Microbial, host and xenobiotic diversity in the cystic fibrosis sputum metabolome[J]. The ISME journal, 2016, 10(6): 1483..

35. Leroy, P. D., Sabri, A., Heuskin, S., Thonart, P., Lognay, G., Verheggen, F. J., Haubruge, E. Microorganisms from aphid honeydew attract and enhance the efficacy of natural enemies[J]. Nature communications, 2011, 2: 348..

36. Stopfer M. Malaria: Mosquitoes bamboozled[J]. Nature, 2011, 474(7349): 40..

37. Lapid, H., Shushan, S., Plotkin, A., Voet, H., Roth, Y., Hummel, T., Sobel, N. Neural activity at the human olfactory epithelium reflects olfactory perception[J]. Nature neuroscience, 2011, 14(11): 1455..

38. Verhulst, N. O., Beijleveld, H., Knols, B. G., Takken, W., Schraa, G., Bouwmeester, H. J., Smallegange, R. C. Cultured skin microbiota attracts malaria mosquitoes[J]. Malaria journal, 2009, 8(1): 302..

39. Carey A F, Wang G, Su C Y, et al. Odorant reception in the malaria mosquito Anopheles gambiae[J]. Nature, 2010, 464(7285): 66..

40. Farhan, A., Gulati, J., Groβe-Wilde, E., Vogel, H., Hansson, B. S., Knaden, M. The CCHamide 1 receptor modulates sensory perception and olfactory behavior in starved Drosophila[J]. Scientific reports, 2013, 3: 2765..

41. Nguyen, M., Sharma, A., Wu, W., Gomi, R., Sung, B., Hospodsky, D., Worgall, S. The fermentation product 2, 3-butanediol alters P. aeruginosa clearance, cytokine response and the lung microbiome[J]. The ISME journal, 2016, 10(12): 2978..

42. Gomez, L., Thiebaut, P. A., Paillard, M., Ducreux, S., Abrial, M., Da Silva, C. C., Ovize, M. The SR/ER-mitochondria calcium crosstalk is regulated by GSK3β during reperfusion injury[J]. Cell death and differentiation, 2016, 23(2): 313..

43. Zimmerman J B, Anastas P T. Toward substitution with no regrets[J]. Science, 2015, 347(6227): 1198-1199..