Michael Addition(Michael Condensation):  Formally a 1,4 addition/conjugate addition of a resonance-stabilized carbanion (the reaction of an active methylene compound such as a malonate to an α,β-unsaturated carbonyl compound or the reaction of a nucleophile with an activated α,β unsaturated system(1). From a practical point of view in biochemistry, a Michael addition is the addition of a nucleophile to a conjugated double bond such the reaction between an acrylate and a thiolate anion (2,3). There is extensive application of the Michael addition in biochemistry(4-12).  It should be noted that Michael addition reactions can be reversible(13-15).   One the best examples in biochemistry is the modification of cysteine residues with N-alkylmaleimide derivatives(16-19). Another important example of the Michael addition in biochemistry and molecular biology is the reaction of 4-hydroxynon-2-enal and other oxidized lipids  with amines (such as lysine) and sulfhydryl groups(20-25). The reaction of oxidized lipids with lysine in protein has been referred to as protein carbonylation(26).

1.  Michael, A., Ueber die Addition von Natriumacetessig und Natriummalonsäurethern zu den Aethern ungesättigter Säuren, J.Prakt.Chem. 35, 349-356, 1886.
2.  Nair, D.P., Podgórski, M., Chatani, S., et al., The thiol-Michael addition click reaction. A powerful and widely used tool in materials chemistry, Chem.Mater. 26, 724-744, 2014.
3. Saraswathy, M., Stansbury, J.W., and Nair, D.P., Thiol-functionalized nanogels as reactive plasticizers for crosslinked polymer networks, J.Mech.Biomed.Mater. 74, 296-303, 2017.
4.  Powell, G.K., Winter, H.C., and Dekker, E.E., Michael addition of thiols with 4-methyleneglutamic acid: preparation of adducts, their properties and presence in peanuts, Biochem.Biophys.Res.Commun. 105, 1361-1367, 1982.
5.  Wang, M., Nishikawa, A. and Chung, F.L., Differential effects of thiols on DNA modifications via alkylation and Michael addition by α-acetoxy-N-nitrosopyrrolidine, Chem.Res.Toxicol. 5, 528-531, 1992.
6.  Jang, D.P., Chang, C.W., and Uang, B.J., Highly diastereoselective Michael addition of α-hydroxy acid derivatives and enantioselective synthesis of (+)-crobarbatic acid, Org.Lett. 3, 983-985, 2001.
7.  Naidu, B.N., Sorenson, M.E., Connolly, T.P., and Ueda, Y., Michael addition of amines and thiols to dehydroalanine amides: a remarkable rate acceleration in water, J.Org.Chem. 68, 10098-10102, 2003.
8.  Weinstein, R., Lerner, R.A., Barbas, C.F., 3rd, and Shabat, D., Antibody-catalyzed asymmetric intramolecular Michael additional of aldehydes and ketones to yield the disfavored cis-product, J.Am.Chem.Soc. 127, 13104-13105, 2005.
9. Dai, H.X., Yao, S.P., and Wang, J., Michael addition of pyrimidine with disaccharide acrylates catalyzed in organic medium with lipase M from Mucor javanicus, Biotechnol.Lett. 28, 1503-1507, 2006.
10.  Grimsrud, P.A., Xie,H., Griffin, T.J., and Berhlohr, D.A., Oxidative stress and covalent modification of protein with bioactive aldehydes, J.Biol.Chem. 283, 21837-21841, 2008l
11. Minko, I.G., Kozekov, I.D., Harris, T.M., et al., Chemistry and biology of DNA containing 1,N2-deoxyguanosine adducts of α,β-unsaturated aldehydes acrolein, crotonaldehyde, and 4-hydroxynonenal, Chem.Res.Toxicol. 22, 759-778, 2009.
12. Oeste, C.L. and Pérez-Sala, D., Modification of cysteine residues by cyclopentenone prostaglandins: interplay with redox regulation of protein function, Mass Spectrom.Rev.33, 110-125, 2014.
13. Johansson, M.H., Reversible Michael additions: covalent inhibitors and prodrugs, Mini Rev.Med.Chem. 12, 1330-1344, 2012.
14. Freeman, B.A., O’Donnell, V.B., and Schopfer, F.J., The discovery of nitro-fatty acids as products of metabolic and inflammatory reactions and mediators of adaptive cell signaling, Nitric Oxide 77, 106-111, 2018.
15. Renault, K., Fredy, J.W., Renard, P.Y., and Sabot, C., Covalent modification of biomolecules through maleimide-based labeling strategies, Bioconjug.Chem. 29, 2497-2513, 2018.
16.  Heitz, J.R., Anderson, C.D., and Anderson, B.M., Inactivation of yeast alcohol dehydrogenase by N-alkylmaleimides, Arch.Biochem.Biophys. 127, 627-636, 1968.
17. Lusty, C.J. and Fasold, H., Characterization of sulfhydryl groups of actin, Biochemistry 8, 2933-2939, 1969.
18.  Bowes, T.J. and Gupta, R.S., Induction of mitochondrial fusion of cysteine-alklyators ethacrynic acid and N-ethylmaleimide, J.Cell Physiol. 202, 796-804, 2005.
19.  Lundblad, R.L., Chemical Reagents for Protein Modification, 3rd edn., CRC Press, Boca Raton, FL, 2014.
20. Winter, C.K., Segall, H.J., and Haddon, W.F., Formation of cyclic adducts of deoxyguanosine with the aldehyde trans-4-hydroxy-2-hexenal and trans-4-hydroxy-2-nonenal in vitro, Cancer Res. 46, 5682-5686, 1986.
21. Sayre, L.M., Arora, P.K., Iyer, R.S., and Salomon, R.G., Pyrrole formation from 4-hydroxyonenal and primary amines, Chem.Res.Toxicol. 6, 19-22, 1993
22. Hartley, D.P., Ruth, J.A., and Petersen, D.R., The hepatocellular metabolism of 4-hydroxynonenal by alcohol dehydrogenase, aldehyde dehydrogenase, and glutathione-S-transferase, Arch.Biochem.Biophys. 316, 197-205, 1995.
23. Engle, M.R., Singh, S.P., Czernik, P.J., et al., Physiological role of mGSTA4-4, a glutathione S-transferase metabolizing 4-hydroxynonenal: generation and analysis of mGst4 null mouse, Toxicol.Appl.Pharmacol. 194, 296-308, 2004.
24. Lopachin, R.M. Gavin, T., and Barber, D.S., Type-2 alkenes mediate synaptotoxicity in neurodegenerative diseases, Neurotoxicity 29, 871-882, 2008.
25. Huang, H., Kozekov, I.D., Kozekova, A., et al., DNA cross-link induced by trans-4-hydroxynonenal, Environ.Mol.Mutagen 51, 625-634, 2010.
26.  Colombo, G., Clerici, M., Garavaglia, M.E., et al., A step-by-step protocol for assaying protein carbonylation in biological samples, J.Chromatog.B.Analyt.Technol.Biomed.Life Sci. 1019, 178-190, 2016.