The interaction of transport mechanisms and intracellular enzymes in metabolizing systems

  • U. Trendelenburg
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 32)


The life span of extracellular catecholamines is limited by the combination of uptake and subsequent intracellular metabolism by either monoamine oxidase (MAO) and/or catechol-O-methyl transferase (COMT). Three such “metabolizing systems” are involved in the inactivation of noradrenaline: 1) Neuronal uptake (high-affinity uptake1 in association with neuronal MAO (and vesicular uptake), 2) extraneuronal uptake (low affinity uptake2) in association with intracellular COMT and MAO (in smooth muscles, myocardial cells, glands), and 3) uptake1 of non-neuronal cells in association with intracellular COMT and/or MAO (in vascular endothelium of rat lung).

Such systems function as “pump and leak systems with enzyme(s) inside”. The analysis of either uptake or enzyme fails to reveal the characteristics of such systems; they are determined by the interaction of both components.

Because of the high activity of these intracellular enzymes, it is unlikely that either COMT or MAO is ever saturated in vivo. However, in vitro saturation of extraneuronal COMT and MAO reveals that extraneuronal COMT is a high-affinity, but extraneuronal MAO a low-affinity enzyme. Hence, membrane-bound COMT appears to be responsible for the extraneuronal O-methylation of noradrenaline.

If intracellular enzymes remain unsaturated, the determination of the rate constants describing the unsaturated enzyme (KENZYME = Vmax/Km) is of particular interest. KENZYME can be determined for metabolizing systems, since this rate constant is not affected by the (usually unknown) fractional size of the metabolizing system.


Monoamine Oxidase Intracellular Enzyme Metabolite Formation Neuronal Uptake Leak System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



catechol-O-methyl transferase


dihydroxymandelic acid




monoamine oxidase


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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • U. Trendelenburg
    • 1
  1. 1.Department of Pharmacology and ToxicologyUniversity of WürzburgWürzburgFederal Republic of Germany

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