Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine
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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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).”
From Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans (2008) · cites this paper as [11]
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Biochemical Assessment of Pheochromocytoma and Paraganglioma
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A Fluorescent Biosensors for Detection Vital Body Fluids’ Agents
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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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