X-Message-Number: 12973 Date: Mon, 20 Dec 1999 21:57:12 -0800 (PST) From: Doug Skrecky <> Subject: could some flavonoids impliment reversible chemical fixation? Authors Murakami S. Muramatsu M. Tomisawa K. Institution Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd., Ohmiya, Japan. Title Inhibition of gastric H+, K(+)-ATPase by flavonoids: a structure-activity study. Source Journal of Enzyme Inhibition. 14(2):151-66, 1999. Abstract Gastric H+, K(+)-ATPase plays a pivotal role in the final step of gastric acid secretion. Over 80 flavonoids, including flavones, flavanones, isoflavones and anthocyanidins were examined for their in vitro effect on gastric H+, K(+)-ATPase and some were found to be inhibitors of this enzyme. Kinetic studies showed that the inhibition of H+, K(+)-ATPase by flavonoids was competitive with respect to ATP, and non-competitive with respect to K+. Structure-activity analysis revealed the following: (1) The inhibitory potency of flavonoids depends on the number of hydroxyl groups up to four per molecule and that above this, no marked enhancement is seen; (2) The hydroxylation pattern is an important determinant of inhibitory potency. Two adjacent hydroxyl groups (catechol-type), three adjacent hydroxyl groups (pyrogallol-type) or hydroxyl groups at C-3, C-5 and C-7 are a minimum requirement for high potency inhibition; (3) Protection of the hydroxyl group(s) by glycosylation or methylation decreases potency; (4) Saturation of the C-2-C-3 double bond results in a decrease in potency; and (5) A ketone at C-4 is not essential for inhibition. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=12973