Concepts of Metabolic Regulation

The ability of animal organisms to perform reductive syntheses of complex macromolecules from simple precursors in the presence of a strongly oxidative and catabolism-promoting environment has been for some a source of great wonderment and speculation. This, however, is not reflected in most bio- 

It is noteworthy that direct measurement of the concentration of the components of cellular redox reactions is not in keeping with this conclusion. Indeed, measurements of actual [NAD ]/[NADH] ratios give values at least one thousandfold too low in relation to the anticipated nearequilibrium value. However, the worth of direct measurement is discounted (in this line of reasoning) on the basis that only freely soluble components could participate in the redox reactions under study. Accordingly, much of the NAD is assumed to be bound and unavailable for reaction. Concentrations of free coenzymes can then be assumed that will, when substituted in the appropriate equations, support the conclusion that each redox reaction is operating near to equilibrium. This circular argument leads to the assumption that 99.9% of cytoplasmic NADH is bound and to a calculated value for free cytoplasmic NADH of less than 1 jjlM, This result 

MICHAEL N. BERRY, ANTHONY R. GRIVELL. and PATRICIA 6. WALLACE 

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