From owner-metabolic-reg@net.bio.net Wed Sep 08 12:42:00 1999 Path: biosci!newshost.lanl.gov!awabi.library.ucla.edu!209.50.235.254!europa.netcrusader.net!205.252.116.205!howland.erols.net!news-out-b.news.pipex.net.MISMATCH!tank.news.pipex.net!pipex!server1.netnews.ja.net!hgmp.mrc.ac.uk!biosci From: JHSH@LAND.SUN.AC.ZA ("Jannie Hofmeyr") Newsgroups: bionet.metabolic-reg Subject: Re: 'key' concepts Date: 8 Sep 1999 14:34:48 +0100 Organization: Stellenbosch University Lines: 48 Message-ID: References: <3.0.6.32.19990908133132.008109e0@csmail.brookes.ac.uk> NNTP-Posting-Host: mercury.hgmp.mrc.ac.uk Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7BIT X-Trace: niobium.hgmp.mrc.ac.uk 936797688 28643 193.62.192.80 (8 Sep 1999 13:34:48 GMT) X-Complaints-To: news@hgmp.mrc.ac.uk NNTP-Posting-Date: 8 Sep 1999 13:34:48 GMT X-Received: from mail.sun.ac.za (mail.sun.ac.za [146.232.128.1]) by hgmp.mrc.ac.uk (8.9.3/8.9.3) with ESMTP id OAA22271 for ; Wed, 8 Sep 1999 14:33:31 +0100 (BST) X-Received: from land.sun.ac.za ([146.232.216.2]) by mail.sun.ac.za with esmtp (Exim 2.10 #1) id 11Ohqk-0006oA-00 for btk-mca@hgmp.mrc.ac.uk; Wed, 8 Sep 1999 15:33:22 +0200 X-Received: from SUN_LAND/SpoolDir by land.sun.ac.za (Mercury 1.44); 8 Sep 99 15:32:27 +0200 X-Received: from SpoolDir by SUN_LAND (Mercury 1.44); 8 Sep 99 15:32:03 +0200 X-To: btk-mca@hgmp.mrc.ac.uk X-Reply-to: jhsh@mail.sun.ac.za X-Priority: normal X-In-reply-to: <3.0.6.32.19990908133132.008109e0@csmail.brookes.ac.uk> X-Mailer: Pegasus Mail for Win32 (v3.12) David wrote > Any other offerings for definitions of 'key metabolite'? As those of you who have followed my and Athel's line of thinking of the last decade or so know, we believe that any notion of 'key' this or that must be linked to the performance in terms of some specified function. So, in my and my student Brett Olivier's recent experiment in metabolic design (as presented in my talk at the resent NATO meeting in Visegrad) we showed that it is possible to design a pathway in such a way that a metabolic function is the responsibility of one enzyme or a group of enzymes. For example, we could show 1. how to ensure that flux-control of a simple biosynthetic pathway lies in the demand for the product of that pathway; 2. how the supply system then automatically becomes responsible for the level and homeostatic maintenance of the product of that pathway; 3. how to ensure that the function in (2) becomes the responsibility of the biosynthetic enzyme with which this product interacts directly (eg. allosterically); etc. In this sense it is possible to quantify the degree to which a specific enzyme is a `key' player in the fullfilment of a certain function. I suppose in some sense the biosynthetic end-product in our designed system is a 'key' metabolite because much of the system has been designed around it. However, whereas we can quantify the `keyness' of an enzyme with respect to some function, I cannot immediately see how to do this with a metabolite. Perhaps this is the difference: an enzyme can play a key role in a function, whereas a metabolite can be key to a design pattern. This is starting to sound too metaphysical so I'd better sign off. Regards to all Jannie Prof. Jannie Hofmeyr Tel: +27 21 808 3039 Dept. of Biochemistry Fax: +27 21 808 3022 University of Stellenbosch e-mail: jhsh@maties.sun.ac.za Private Bag X1 Matieland 7602 Stellenbosch South Africa --- .