The effect of age upon the affinity of microsomal mono-oxygenase enzymes for substrate in human liver.

Although the clearance of many oxidized drugs falls with age, a corresponding fall in the maximal activities of drug metabolizing enzymes has not been noted. The possibility of a fall in enzyme affinity for substrate with age, which could account for the observed changes, has not previously been investigated in human liver. We have studied the kinetics of the microsomal mono-oxygenase 7-ethoxycoumarin-O-de-ethylase in 17 human liver biopsy specimens. No correlation was observed between age and microsomal protein recovery, maximal enzyme activity or apparent enzyme affinity. Since microsomal mono-oxygenase activities and affinities appear not to change in human liver, other factors such as a fall in liver volume or blood flow must be responsible for the decline in clearance of many oxidized drugs which occurs with ageing.