Acetoxy drug: protein transacetylase: A novel enzyme-mediating protein acetylation by polyphenolic peracetates

Raj, Hanumantharao G.; Singh, Brajendra K.; Kohli, Ekta; Dwarkanath, Bilikere S.; Jain, Subhash C.; Rastogi, Ramesh C.; Kumar, Ajit; Adhikari, J. S.; Watterson, Arthur C.; Olsen, Carl E.; Parmar, Virinder S.

doi:10.1351/pac200577010245

Pure Appl. Chem., 2005, Vol. 77, No. 1, pp. 245-250

http://dx.doi.org/10.1351/pac200577010245

Acetoxy drug: protein transacetylase: A novel enzyme-mediating protein acetylation by polyphenolic peracetates

Hanumantharao G. Raj¹, Brajendra K. Singh², Ekta Kohli¹, B. S. Dwarkanath³, Subhash C. Jain², Ramesh C. Rastogi², Ajit Kumar¹, J. S. Adhikari³, Arthur C. Watterson⁴, Carl E. Olsen⁵ and Virinder S. Parmar²

¹ Biochemistry Department, V. P. Chest Institute, University of Delhi, Delhi 110 007, India
² Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India
³ Institute of Nuclear Medicine and Allied Sciences, Lucknow Road, Delhi 110 054, India
⁴ INSET, Department of Chemistry, University of Massachusetts, Lowell, MA 01854, USA
⁵ Department of Chemistry, Royal Veterinary and Agricultural University, DK-1871 Frederiksburg C, Copenhagen, Denmark

Abstract: The acetylation of proteins in biological systems is largely catalyzed by specific acetyl transferases utilizing acetyl CoA as the acetyl donor. The enzymatic acetylation of proteins independent of acetyl CoA was unknown until we discovered a unique membrane-bound enzyme in mammalian cells catalyzing the transfer of acetyl groups from polyphenolic peracetates (PAs) to certain enzyme proteins, resulting in the modulation of their catalytic activities. Since for the enzyme, acetyl derivatives of several classes of polyphenols such as coumarins, flavones, chromones, and xanthones were found to be acetyl donors, the enzyme was termed as acetoxy drug: protein transacetylase (TAase). TAase was found to be ubiquitously present in tissues of several animal species and a variety of animal cells. Liver microsomal cytochrome P-450 (CYP), NADPH-cytochrome c reductase and cytosolic glutathione S-transferase (GST) were found to be the targets for TAase-catalyzed acetylation by the model acetoxy drug 7,8-diacetoxy-4-methylcoumarin (DAMC). Accordingly, the catalytic activities of CYP-linked, mixed function oxidases (MFOs) and GST were irreversibly inhibited while the reductase was remarkably activated. In this report, we have reviewed the details concerning purification and characterization of TAase and the protein acetylation by DAMC. Quantitative structure–activity relationship (QSAR) studies concerning the specificities of various PAs to liver microsomal TAase and TAase-related biological effects have also been reviewed.