From the foregoing considerations, the
energy-linked transhydrogenase reaction emerges as a powerful and flexible
element in the network of redox and energy interrelationships that integrate mitochondrial and cytosolic metabolism. Its thermodynamic features make it possible for the reaction to respond readily to challenges, either on the side of
NADPH utilization or on the side of energy depletion. Yet, the kinetic features are designed to prevent a wasteful input of energy when other sources of reducing equivalents to
NADP are available, or to deplete the redox potential of
NADPH in other than emergency conditions. By virtue of these characteristics, the
energy-linked transhydrogenase can act as an effective
buffer system, guarding against an excessive depletion of
NADPH, preventing uncontrolled changes in key metabolites associated with
NADP-dependent
enzymes and calling on the supply of reducing equivalents from
NAD-linked substrates only under conditions of high demand for
NADPH. At the same time, it can provide an emergency protection against a depletion of energy, especially in situations of
anoxia where a supply of reducing equivalents through
NADP-linked substrates can be maintained. The flexibility of this design makes it possible that the functions of the
energy-linked transhydrogenase vary from one tissue to another and are readily adjustable to different metabolic conditions.