From owner-metabolic-reg@net.bio.net Mon Sep 02 23:00:00 1996
Path: biosci!daresbury!not-for-mail
From: daf@bms.brookes.ac.uk (David Fell)
Newsgroups: bionet.metabolic-reg
Subject: Re: Phenotype of mito. aconitase knockout?
Date: 3 Sep 1996 11:09:13 +0100
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David Huen wrote:

>I am attempting to predict the consequence of the genetic knockout of the
>mitochondrial form of aconitase and would appreciate your assistance. This
>seems the likeliest group to get an answer from.
>
>Presumably, the loss of mito. aconitase will lead to accumulation of
>citrate within the mitochondrion. Can this be exported out of the
>mitochondrion into the cytosol? If so, will cytosolic aconitase convert it
>to isocitrate and can this isocitrate been imported back into the
>mitochondrion? That is, to what extent can cytosolic aconitase complement a
>loss of mito. aconitase?
>
Well, it's probably tissue dependent, but yes citrate can be transported out 
(it is for fat synthesis as a matter of course), and there is a cytosolic 
aconitase. 
A best guess would be that cytosolic aconitase moght handle the flux in 
tissues without extreme energy demands, but that metabolite levels would be 
significantly altered.

>Going on further, is there a cytosolic isocitrate dehydrogenase that can
>convert isocitrate to alfa-ketoglutarate and is this intermediate
>importable into the mitochondrion?
>
Yes there is.  It is NADP-linked, and potentially maintains the cytosolic 
NADPH levels.  Alpha ketoglutarate can get back in OK.  Using this step 
would have implications for the cytosolic redox state and might affect other 
pathways (e.g. pentose pathway) that are also linked to this.

If they can actually fly with this mutation, I doubt you'd find it easy to 
spot any other phenotype.

David Fell


=========================================================

David Fell,
School of Biological & Molecular Sciences,
Oxford Brookes University,
Oxford OX3 0BP,           Tel. +44 (0)1865 483247
UK                        FAX  +44 (0)1865 484017

daf@bms.brookes.ac.uk

See my book at:  http://www.portlandpress.co.uk/books/isbn/185578047X.htm


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