The modification of the kinetics of tyrosine hydroxylase in vitro and in vivo: a possible role for carboxymethylation in the regulation of L-dopa synthesis

Abstract

The control of the synthesis of neurotransmitters is of fundamental importance, none more so than that of L-dopa which is the precursor of noradrenaline and dopamine in the brain. In this laboratory our interest lies in the changes in dopamine metabolism which are associated with abnormal behaviour. We have for some time been particularly interested in the kinetic changes which occur in activity of the enzyme tyrosine hydroxylase (TH) in response to external stimuli and drugs (e.g., neuroleptics). In examining the kinetics of TH two parameters are of importance. These are the maximal velocity (Vmax) which is correctly expressed as the amount of product synthesised when the enzyme’s active centres are saturated with all three substrates (oxygen, tyrosine and tetrahydrobiopterin), and the Michaelis constant (Km) which is expressed as the concentration producing half maximal velocity when the other two substrates are again saturating. Similar constants can also be measured in the presence of subsaturating substrate concentrations, hence these are referred to as the substrate constant Ks (rather than Km) and Vmax’ (rather than Vmax).