Catecholamine biosynthesis and physiological regulation in neuroendocrine cells.
The catecholamines are widely distributed in mammals and their levels and physiological functions are regulated at many sites. These include their release from neuroendocrine cells, the type and sensitivity of the multiple receptors in target cells, the efficacy of the reuptake system in the secretory cells, and the rates of catecholamine biosynthesis and degradation. In the present review the main focus will be on the more recent studies on the biosynthesis in neuroendocrine cells which involves a specific set of enzymes, with special reference to physiologically important regulatory mechanisms. Eight enzymes of the biosynthetic pathway have now been identified, cloned, expressed as recombinant proteins, characterized with respect to catalytic and regulatory properties, and some of them also crystallized. The identification of the tyrosine hydroxylase catalysed reaction as the rate-limiting step in the normal catecholamine biosynthesis has attracted most attention, both in terms of transcriptional and post-translational regulation. In certain human genetic disorders of catecholamine biosynthesis other enzymes in the pathway may become rate-limiting, notably those involved in the biosynthesis/regeneration of the natural co-factor tetrahydrobiopterin in the tyrosine hydroxylase reaction. The enzymes involved seem to be regulated by a variety of physiological factors, both on a long-term scale and a short-term basis, and include the relative rates of synthesis, degradation and state of activation of the biosynthetic enzymes, notably of tyrosine hydroxylase. Multiple surface receptors and signalling pathways are activated in response to extracellular stimuli and play an essential role in the regulation of catecholamine biosynthesis.
Flatmark
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Department of Biochemistry and Molecular Biology, University of Bergen, Bergen, Norway.
D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D055598:Chemical Phenomena; D002621:Chemistry; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008659:Metabolic Diseases / Q000235:genetics; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009490:Neurosecretory Systems / Q000166:cytology / Q000378:metabolism*
D002395:Catecholamines; D004798:Enzymes