Cited by 1,072Metabolism and Genetic DisordersNeuroscience and Neuropharmacology ResearchPharmacogenetics and Drug Metabolism

Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine

Eisenhofer, Graeme, Kopin, Irwin J., Goldstein, David S.·2004·Pharmacological Reviews

Abstract

This article provides an update about catecholamine metabolism, with emphasis on correcting common misconceptions relevant to catecholamine systems in health and disease. Importantly, most metabolism of catecholamines takes place within the same cells where the amines are synthesized. This mainly occurs secondary to leakage of catecholamines from vesicular stores into the cytoplasm. These stores exist in a highly dynamic equilibrium, with passive outward leakage counterbalanced by inward active transport controlled by vesicular monoamine transporters. In catecholaminergic neurons, the presence of monoamine oxidase leads to formation of reactive catecholaldehydes. Production of these toxic aldehydes depends on the dynamics of vesicular-axoplasmic monoamine exchange and enzyme-catalyzed conversion to nontoxic acids or alcohols. In sympathetic nerves, the aldehyde produced from norepinephrine is converted to 3,4-dihydroxyphenylglycol, not 3,4-dihydroxymandelic acid. Subsequent extraneuronal O-methylation consequently leads to production of 3-methoxy-4-hydroxyphenylglycol, not vanillylmandelic acid. Vanillylmandelic acid is instead formed in the liver by oxidation of 3-methoxy-4-hydroxyphenylglycol catalyzed by alcohol and aldehyde dehydrogenases. Compared to intraneuronal deamination, extraneuronal O-methylation of norepinephrine and epinephrine to metanephrines represent minor pathways of metabolism. The single largest source of metanephrines is the adrenal medulla. Similarly, pheochromocytoma tumor cells produce large amounts of metanephrines from catecholamines leaking from stores. Thus, these metabolites are particularly useful for detecting pheochromocytomas. The large contribution of intraneuronal deamination to catecholamine turnover, and dependence of this on the vesicular-axoplasmic monoamine exchange process, helps explain how synthesis, release, metabolism, turnover, and stores of catecholamines are regulated in a coordinated fashion during stress and in disease states.

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Crossref · 10.1124/pr.56.3.1

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  • Norepinephrine leaking from storage granules or recaptured after release by sympathetic nerves is deaminated to plasma dihydroxyphenylglycol (DHPG), which is almost completely derived from metabolism of neuronal norepinephrine.

    “Norepinephrine leaking from storage granules or norepinephrine recaptured after release by sympathetic nerves is deaminated to plasma dihydroxyphenylglycol (DHPG), which is almost completely derived from metabolism of neuronal norepinephrine (11).”

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Authors
Eisenhofer, G., Kopin, I. J., & Goldstein, D. S.
Affiliations
National Institutes of Health (US)
Venue
Pharmacological Reviews
Publisher
Elsevier BV
Published
2004-09
Volume
56
Issue
3
Pages
331-349
ISSN
0031-6997 (ISSN-L)
OpenAlex
W2141410612
Cited by
1,072
References
229
Citations by year
2026: 47 · 2025: 58 · 2024: 54 · 2023: 56 · 2022: 56 · 2021: 81 · 2020: 55 · 2019: 71 · 2018: 60 · 2017: 57 · 2016: 63 · 2015: 51 · 2014: 56 · 2013: 61 · 2012: 49
FWCI
13.94
Type
journal article
Language
en
Open access
closed
Locations
  • Pharmacological Reviews (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
catecholamine metabolism, catecholamine stores, vesicular monoamine transporter, monoamine oxidase, norepinephrine, epinephrine, 3,4-dihydroxyphenylglycol, vanillylmandelic acid, MHPG, metanephrine, pheochromocytoma, sympathetic nerves, catecholamine turnover
MeSH terms
Animals, Biological Transport, Active, Catecholamines, Humans, Models, Biological, Molecular Structure

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