From owner-btk-mca@hgmp.mrc.ac.uk Fri Jun 9 10:34:00 2000 Return-Path: Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 110) id 7F71917AF2; Fri, 9 Jun 2000 10:33:59 +0100 (BST) Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 6024) id 1D32A17AEF; Fri, 9 Jun 2000 10:33:58 +0100 (BST) Received: from niobium.hgmp.mrc.ac.uk (niobium [193.62.192.41]) by mercury.hgmp.mrc.ac.uk (Postfix) with ESMTP id 97FDA415D4 for ; Fri, 9 Jun 2000 10:33:57 +0100 (BST) Received: (from news@localhost) by niobium.hgmp.mrc.ac.uk (8.9.3+Sun/8.8.8) id KAA16066 for btk-mca-list@hgmp.mrc.ac.uk; Fri, 9 Jun 2000 10:33:57 +0100 (BST) X-Authentication-Warning: niobium.hgmp.mrc.ac.uk: news set sender to using -f From: gcb@mole.bio.cam.ac.uk ("Guy C. Brown") X-Newsgroups: bionet.metabolic-reg Subject: Re: Phosphofructokinase controls glycolysis (or not?) Date: 9 Jun 2000 10:33:56 +0100 Organization: BIOSCI/MRC Human Genome Mapping Project Resource Centre Lines: 36 Message-ID: <3.0.5.32.20000609103720.00897600@mole.bio.cam.ac.uk> References: <3.0.5.32.20000607180841.0089fce0@mole.bio.cam.ac.uk> Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" X-Trace: niobium.hgmp.mrc.ac.uk 960543236 16064 193.62.192.80 (9 Jun 2000 09:33:56 GMT) X-Complaints-To: news@net.bio.net X-Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 6024) id 11EDD17AEF; Fri, 9 Jun 2000 10:33:54 +0100 (BST) X-Received: from mole.bio.cam.ac.uk (mole.bio.cam.ac.uk [131.111.36.9]) by mercury.hgmp.mrc.ac.uk (Postfix) with ESMTP id 5215B415D4 for ; Fri, 9 Jun 2000 10:33:54 +0100 (BST) X-Received: from [131.111.36.50] (helo=agm.bioc.cam.ac.uk) by mole.bio.cam.ac.uk with smtp (Exim 1.92 #3) for btk-mca@hgmp.mrc.ac.uk id 130LAj-000fy9-00; Fri, 9 Jun 2000 10:33:49 +0100 X-Sender: gcb@mole.bio.cam.ac.uk X-Mailer: QUALCOMM Windows Eudora Light Version 3.0.5 (32) X-To: btk-mca@hgmp.mrc.ac.uk X-In-Reply-To: <393FF7A5.C414F6D2@biokin.com> To: btk-mca@hgmp.mrc.ac.uk Sender: owner-btk-mca@hgmp.mrc.ac.uk Precedence: bulk Petr Kuzmic wrote: >I suppose everybody remembers Knowles' et al. 1980s work on the >energetics of the "perfect enzyme". >Maybe the horrendous formalism that Knowles at al. invented for their >"perfect enzyme" work could be subjected to yet another kind of torture, >and cast in terms of MCA?? We did subject their "perfect enzyme" triose phosphate isomerase to this "MCA torture", and found that it was not "perfect" at all - i.e. the catalytic step had a significant control coefficient over kcat/Km, thus increasing the rate constants of the catalytic step will increase the rate at low substrate concentrations, thus the enzyme could evolve to be significantly faster. Thus the normal criteria used for catalytic perfection (a kcat/Km "approching" the diffusion limit) can be misleading. We have also subjected 3 beta-lactamases (which have been claimed to be perfect using similar criteria) to similar torture, and found them to be similarly less than perfect. It is interesting to note that "perfect" enzymes in this sense are meant to be entirely limited by the substrate binding step, whereas the equilibrium binding assumption used in much enzymology/ transition state theory assumes the opposite - that the catalytic step is entirely rate limiting. Dr Guy C. Brown Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. Tel: (44) (0)1223 333342 Fax: (44) (0)1223 333345 e-mail: gcb@mole.bio.cam.ac.uk http://www.bio.cam.ac.uk/dept/biochem/brown --- .