Distinct Effect of Benzalkonium Chloride on the Esterase and Aryl Acylamidase Activities of Butyrylcholinesterase.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) from vertebrates, other than their predominant acylcholine hydrolase (esterase) activity, display a genuine aryl acylamidase activity (AAA) capable of hydrolyzing the synthetic substrate o-nitroacetanilide to o-nitroaniline. This AAA activity is strongly inhibited by classical cholinesterase (ChE) inhibitors. In the present study, benzalkonium chloride (BAC), a cationic detergent widely used as a preservative in pharmaceutical preparations, has been shown to distinctly modulate the esterase and AAA activities of BChEs. The detergent BAC was able to inhibit the esterase activity of human serum and horse serum BChEs and AChEs from electric eel and human erythrocyte. The remarkable property of BAC was its ability to profoundly activate the AAA activity of human serum and horse serum BChEs but not the AAA activity of AChEs. Thus BAC seem to preferentially activate the AAA activity of BChEs alone. Results of the study using the ChE active site-specific inhibitor diisopropyl phosphorofluoridate indicated that BAC binds to the active site of ChEs. Furthermore, studies using a structural homolog of BAC indicated that the alkyl group of BAC is essential not only for its interaction with ChEs but also for its distinct effect on the esterase and AAA activities of BChEs. This is the first report of a compound that inhibits the esterase activity, while simultaneously activating the AAA activity, of BChEs. Copyright 2000 Academic Press.

[1]  C. J. Vidal,et al.  Inhibition of cholinesterases by the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) , 1991 .

[2]  M. Froment,et al.  Asp7O in the peripheral anionic site of human butyrylcholinesterase. , 1996, European journal of biochemistry.

[3]  C. Bhanumathy,et al.  Noncholinergic functions of cholinesterases , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[4]  M. Kamal.  Investigation of the effect of lannate on kinetic parameters of acetylcholinesterase: Slightly concave mixed‐type of inhibition system , 1997, Biochemistry and molecular biology international.

[5]  A. Goldman,et al.  Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein , 1991, Science.

[6]  A. Main.  Affinity and Phosphorylation Constants for the Inhibition of Esterases by Organophosphates , 1964, Science.

[7]  D. Quinn,et al.  Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition states , 1987 .

[8]  A. Goldberg,et al.  Biology of cholinergic function , 1976 .

[9]  R. Boopathy,et al.  Chemical modification of the bifunctional human serum pseudocholinesterase. Effect on the pseudocholinesterase and aryl acylamidase activities. , 1985, European journal of biochemistry.

[10]  J. Hubbard,et al.  The Peripheral Nervous System , 1974, Springer US.

[11]  P. Layer,et al.  Cholinesterases in avian neurogenesis. , 1994, International review of cytology.

[12]  A. Gnatt,et al.  Intramolecular relationships in cholinesterases revealed by oocyte expression of site‐directed and natural variants of human BCHE. , 1992, The EMBO journal.

[13]  K. Courtney,et al.  A new and rapid colorimetric determination of acetylcholinesterase activity. , 1961, Biochemical pharmacology.

[14]  G. Alles,et al.  CHOLINESTERASES IN THE BLOOD OF MAN , 1940 .

[15]  J. Grosfeld,et al.  The effect of a neurotoxin (benzalkonium chloride) on the lower esophagus. , 1989, The Journal of surgical research.

[16]  L. Goodman,et al.  The Pharmacological Basis of Therapeutics , 1941 .

[17]  S. George,et al.  The aryl acylamidases and their relationship to cholinesterases in human serum, erythrocyte and liver. , 1981, European journal of biochemistry.

[18]  A. S. Balasubramanian,et al.  The inhibition of brain aryl acylamidase by 5-hydroxytryptamine and acetylcholine. , 1977, Biochemical pharmacology.

[19]  P. Layer,et al.  Novel functions of cholinesterases in development, physiology and disease. , 1995, Progress in histochemistry and cytochemistry.

[20]  B. Uvnäs.  The Effect of Enterogastrone on the Gastric Secretion of the Cat Stimulated toy Continuous Administration of Histamine , 1948 .

[21]  A. Gnatt,et al.  Excavations into the active-site gorge of cholinesterases. , 1992, Trends in biochemical sciences.

[22]  P. Layer,et al.  Aryl acylamidase activity exhibited by butyrylcholinesterase is higher in chick than in horse, but much lower than in fetal calf serum , 1998, Neuroscience Letters.

[23]  Y. Takikawa,et al.  Actions of benzalkonium chloride as a potent depressant at the neuromuscular junction , 1993, Neuropharmacology.

[24]  R. Patarca,et al.  Effects of benzalkonium salts on eukaryotic and microbial G-protein-mediated processes and surface membranes. , 1995, Critical reviews in oncogenesis.

[25]  B. Raman,et al.  Molten-Globule State of Carbonic Anhydrase Binds to the Chaperone-like α-Crystallin* , 1996, The Journal of Biological Chemistry.

[26]  P. Taylor,et al.  Amino acid residues controlling acetylcholinesterase and butyrylcholinesterase specificity. , 1993, Biochemistry.

[27]  R. Rao,et al.  Isolation of a galactose-free 20-kDa fragment exhibiting butyrylcholine esterase and aryl acylamidase activity from human serum butyrylcholine esterase by limited alpha-chymotrypsin digestion. , 1989, European journal of biochemistry.

[28]  D. Small,et al.  Non-classical actions of cholinesterases: Role in cellular differentiation, tumorigenesis and Alzheimer's disease , 1996, Neurochemistry International.

[29]  S. George,et al.  The identity of the serotonin-sensitive aryl acylamidase with acetylcholinesterase from human erythrocytes, sheep basal ganglia and electric eel. , 1980, European journal of biochemistry.