Some funny ideas floating about here. In teaching cell metabolism I have
always used 'ball park' figures of 0.1% reduction for cytosolic NAD (e.g.
liver) and 10% for mitochondrial (Veech,R.L.,Raijman, L., & Krebs, H.A.
Biochem. J. (1970) 117, 499-503). This enables one to fit conveniently most
of the other soluble ratios in the cell (malate/OAA, etc) as well as redox
states in the mitochondrion. The mitochondrial and cytosolic pools may or
may not ever be in electrochemical equilibrium but remember that the
glutamate-aspartate exchange is proton-linked. So a 100-fold difference in
ratio is far from impossible (corresponding to the energy of bringing a +ve
charge from -120 mV). According to Helmut Sies (1982, Metabolic
Compartmentation (Academic Press) p.214) the redox potential of cytosolic
NAD is between -240 and -248mV in normal fed rat livers. This translates to
a log ratio of between 72/30 and 80/30 or a ratio of 250 to 500 (0.2-0.4%
reduction). Sies also has mitochondrial NAD at -318mV or 45% reduction
(also a 100-fold difference in ratios between the two compartments). Much
of this is classical work going back to Bucher & Klingenberg (1958) Angew.
Chem. 70, 552-570. If Martin Klingenberg was in this email group we would
undoubtedly have seen several flames by now! Hans Krebs might have had a
word to say too (cf.the reference above and Williamson ,D.H.,Lund,P. &
Krebs ,H.A. (1967) Biochem. J. 103, 514) tho it's hard to imagine him
flying to the keyboard to log onto anything...) 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, and then (if that
does not suffice) channelling....but we won't go into that...
Peter Nicholls.
