re-post:
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From: dbk at aber.ac.uk (Douglas B. Kell)
Newsgroups: bionet.metabolic-reg
Subject: Re: NAD/NADH ratio
Date: 24 Sep 1994 11:42:11 GMT
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In article <9409232055.AA17399 at spartan.ac.BrockU.CA> pnicholl at SPARTAN.AC.BROCKU.CA writes:
[chomp]
>One of the 'classical'
>BTK-type problems is to take all the known concentrations and ratios in
>cytosol and mitochondrion and then get metabolism to work in a sensible
>direction. It usually doesn't work out too well, and the escape hatch is to
>talk about 'bound' forms of substrates and cofactors,
Well this is a perfectly good 'escape hatch' since, *experimentally*, more NADH
than NAD is bound, and (particularly) more ADP than ATP is bound. (This is one
of the useful fiding to come from NMR.) The magnitude of these effects on the
calculated free energy changes for various reactions is VERY substantial.
>and then (if that
>does not suffice) channelling....but we won't go into that...
Oh do let's. Since you are good enough to cite the right literature on
pyridine nucleotide ratios, let's not ignore the voluminous and
overwhelming evidence for channelling in pyridine nucleotide-linked
dehydrogenase pairs. Whilst some of the folk who would prefer channelling
to go away choose to ignore this (relying on muddying the water by
focussing on overly complex kinetic schemes - the level of debate may
be gauged by papers with titles like the following: Wu, X., Gutfreund, H.,
Lakatos, S. & Chock, P. B. (1991). Substrate channeling in
glycolysis: a phantom phenomenon. Proc. Natl. Acad. Sci. USA 88, 497-501),
the killer proof is the anomeric specificity in which channelling
dehydrogenases use either the A or the B form of NADH while
non-channelling ones don't care. See e.g.:
Srivastava, D. K. & Bernhard, S. A. (1985). Mechanism of transfer of
reduced nicotinamide adenine dinucleotide among dehydrogenases.
Biochemistry 24, 623-628.
Srivastava, D. K. & Bernhard, S. A. (1986). Enzyme-enzyme interactions
and the regulation of metabolic reaction pathways.
Curr. Top. Cell. Reg. 28, 1-68. [Best review!]
Srivastava, D. K., Bernhard, S. A., Langridge, R. & McClarin, J.A.
(1985). Molecular basis for the transfer of nicotiniamide adenine
dinucleotide among dehydrogenases. Biochemistry 24, 629-635.
Srivastava, D. K., Smolen, P., Betts, G. F., Fukushima, T., Spivey, H. O.
& Bernhard, S. A. (1989). Direct transfer of NADH between alpha-glycerol
phosphate dehydrogenase and lactate dehydrogenase: fact or misinterpretation?
Proc. Natl. Acad. Sci. USA 86, 6464-6468.
Do not permit anyone to claim an informed opinion on these matters and to
come to any conclusion about the existence or otherwise of channelling
in these systems if they are unwilling to explain the A- and B-form data!
A recent overview of some areas of channelling, with varying levels of
theology, may be found in a special issue of the J Theoret Biol,
vol 152 part 1 (1991).
When the publishers choose to get their finger out, another review
will be:
Mendes, P., Kell, D.B. & Welch, G.R. (199x) Metabolic channelling in
organized enzyme systems: experiments and models
In: Enzymology in vivo (ed. K. Brindle), Plenum, in the press.
Readers of this group may also be interested to know that there will
be a Gordon Research Conference on Enzyme Organization and Cell
Function, concentrating on many pertinent areas, to be held in the
very agreeable Casa Sirena Marina location, Oxnard, CA January 15-20
1995. The Chair is Murray Deutscher, co-Chair Jim Clegg. Highly
recommended. There will be the usual ad in Science in (I think)
the October 13 issue, but applications can be made to GRC beforehand.
--
Peter Hinxman, Computer Unit | "Charlie Chaplin films ? I find them as
University of Wales, Aberystwyth | funny as getting an arrow through the
Uned Gyfrifiadur,Prifysgol Cymru | neck and then discovering there's a gas
mph at aber.ac.uk Tel:0970-622349 | bill attached to it." ( Blackadder )
