The interaction of transport mechanisms and intracellular enzymes in metabolizing systems
- U. TrendelenburgAffiliated withDepartment of Pharmacology and Toxicology, University of Würzburg
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.
- The interaction of transport mechanisms and intracellular enzymes in metabolizing systems
- Book Title
- Amine Oxidases and Their Impact on Neurobiology
- Book Subtitle
- Proceedings of the 4th International Amine Oxidases Workshop, Würzburg, Federal Republic of Germany, July 7–10, 1990
- pp 3-18
- Print ISBN
- Online ISBN
- Series Title
- Journal of Neural Transmission
- Series Volume
- Series ISSN
- Springer Vienna
- Copyright Holder
- Additional Links
- Industry Sectors
- eBook Packages
- Editor Affiliations
- 1. Department of Psychiatry, University of Wurzburg
- 2. Israel Institute of Technology, Technion
- Author Affiliations
- 3. Department of Pharmacology and Toxicology, University of Würzburg, Versbacher Strasse 9, D-8700, Würzburg, Federal Republic of Germany
To view the rest of this content please follow the download PDF link above.