Catecholamine

A catecholamine (/ˌkætəˈkoʊləmiːn/; abbreviated CA) is a monoamine

neurotransmitter, an organic compound that has a catechol (benzene with Catecholamines
two hydroxyl side groups next to each other) and a side-chain amine.[1]

Catechol can be either a free molecule or a substituent of a larger

molecule, where it represents a 1,2-dihydroxybenzene group.

Catecholamines are derived from the amino acid tyrosine, which is

derived from dietary sources as well as synthesis from phenylalanine.[2] Epinephrine (Adrenaline)
Catecholamines are water-soluble and are 50% bound to plasma proteins
in circulation.

Included among catecholamines are epinephrine (adrenaline),

norepinephrine (noradrenaline), and dopamine. Release of the hormones
epinephrine and norepinephrine from the adrenal medulla of the adrenal Norepinephrine (Noradrenaline)
glands is part of the fight-or-flight response.[3]

Tyrosine is created from phenylalanine by hydroxylation by the enzyme

phenylalanine hydroxylase. Tyrosine is also ingested directly from dietary
protein. Catecholamine-secreting cells use several reactions to convert Dopamine
tyrosine serially to L -DOPA and then to dopamine. Depending on the cell
type, dopamine may be further converted to norepinephrine or even
further converted to epinephrine.[4]

Various stimulant drugs (such as a number of substituted amphetamines) are

catecholamine analogues.
Catechol

Contents
Structure
Production and degradation
Location
Biosynthesis
Degradation
Function
Modality
Effects
Function in plants
Testing for catecholamines
See also
References
External links
Structure
Catecholamines have the distinct structure of a benzene ring with two hydroxyl groups, an intermediate
ethyl chain, and a terminal amine group. Phenylethanolamines such as norepinephrine have a hydroxyl
group on the ethyl chain.

Production and degradation

Biosynthetic pathways for catecholamines and trace amines in the human brain[5][6][7]

AADC PNMT

L -Phenylalanine Phenethylamine N-Methylphenethylamine

AAAH

PNMT
AADC N-Methyltyramine

L -Tyrosine p-Tyramine DBH

AAAH brain minor

CYP2D6 pathway p-Octopamine
PNMT
AADC
primary

pathway
L -DOPA Dopamine

DBH COMT Synephrine

PNMT

Epinephrine Norepinephrine 3-Methoxytyramine

In humans, catecholamines (shown in yellow) are derived from the amino acid L-phenylalanine.

L-Phenylalanine is converted into L-tyrosine by an aromatic amino acid hydroxylase (AAAH)

enzyme (phenylalanine 4-hydroxylase), with molecular oxygen (O2) and tetrahydrobiopterin as
cofactors. L-Tyrosine is converted into L-DOPA by another AAAH enzyme (tyrosine 3-hydroxylase)
with tetrahydrobiopterin, O2, and ferrous iron (Fe2+) as cofactors. L-DOPA is converted into dopamine
by the enzyme aromatic L-amino acid decarboxylase (AADC), with pyridoxal phosphate as the
cofactor. Dopamine itself is also used as precursor in the synthesis of the neurotransmitters
norepinephrine and epinephrine. Dopamine is converted into norepinephrine by the enzyme dopamine
β-hydroxylase (DBH), with O2 and L-ascorbic acid as cofactors. Norepinephrine is converted into
epinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT) with S-adenosyl-L-
methionine as the cofactor.

Location
Catecholamines are produced mainly by the chromaffin cells of the adrenal medulla and the postganglionic
fibers of the sympathetic nervous system. Dopamine, which acts as a neurotransmitter in the central nervous
system, is largely produced in neuronal cell bodies in two areas of the brainstem: the ventral tegmental area
and the substantia nigra, the latter of which contains neuromelanin-pigmented neurons. The similarly
neuromelanin-pigmented cell bodies of the locus coeruleus produce norepinephrine. Epinephrine is
produced in small groups of neurons in the human brain which express its synthesizing enzyme,
phenylethanolamine N-methyltransferase;[8] these neurons project from a nucleus that is adjacent
(ventrolateral) to the area postrema and from a nucleus in the dorsal region of the solitary tract.[8]

Biosynthesis

Dopamine is the first catecholamine synthesized from DOPA. In turn, norepinephrine and epinephrine are
derived from further metabolic modification of dopamine. The enzyme dopamine hydroxylase requires
copper as a cofactor (not shown in the diagram) and DOPA decarboxylase requires PLP (not shown in the
diagram). The rate limiting step in catecholamine biosynthesis through the predominant metabolic pathway
is the hydroxylation of L -tyrosine to L -DOPA.

Catecholamine synthesis is inhibited by alpha-methyl-p-tyrosine (AMPT), which inhibits tyrosine

hydroxylase.

The amino acids phenylalanine and tyrosine are precursors for catecholamines. Both amino acids are found
in high concentrations in blood plasma and the brain. In mammals, tyrosine can be formed from dietary
phenylalanine by the enzyme phenylalanine hydroxylase, found in large amounts in the liver. Insufficient
amounts of phenylalanine hydroxylase result in phenylketonuria, a metabolic disorder that leads to
intellectual deficits unless treated by dietary manipulation. Catecholamine synthesis is usually considered to
begin with tyrosine. The enzyme tyrosine hydroxylase (TH) converts the amino acid L -tyrosine into 3,4-
dihydroxyphenylalanine (L -DOPA). The hydroxylation of L -tyrosine by TH results in the formation of the
DA precursor L -DOPA, which is metabolized by aromatic L -amino acid decarboxylase (AADC; see
Cooper et al., 2002) to the transmitter dopamine. This step occurs so rapidly that it is difficult to measure L -
DOPA in the brain without first inhibiting AADC. In neurons that use DA as the transmitter, the
decarboxylation of L -DOPA to dopamine is the final step in formation of the transmitter; however, in those
neurons using norepinephrine (noradrenaline) or epinephrine (adrenaline) as transmitters, the enzyme
dopamine β-hydroxylase (DBH), which converts dopamine to yield norepinephrine, is also present. In still
other neurons in which epinephrine is the transmitter, a third enzyme phenylethanolamine N-
methyltransferase (PNMT) converts norepinephrine into epinephrine. Thus, a cell that uses epinephrine as
its transmitter contains four enzymes (TH, AADC, DBH, and PNMT), whereas norepinephrine neurons
contain only three enzymes (lacking PNMT) and dopamine cells only two (TH and AADC).

Degradation

Catecholamines have a half-life of a few minutes when circulating in the blood. They can be degraded
either by methylation by catechol-O-methyltransferases (COMT) or by deamination by monoamine
oxidases (MAO).

MAOIs bind to MAO, thereby preventing it from breaking down catecholamines and other monoamines.

Catabolism of catecholamines is mediated by two main enzymes: catechol-O-methyltransferase (COMT)

which is present in the synaptic cleft and cytosol of the cell and monoamine oxidase (MAO) which is
located in the mitochondrial membrane. Both enzymes require cofactors: COMT uses Mg2+ as a cofactor
while MAO uses FAD. The first step of the catabolic process is mediated by either MAO or COMT which
depends on the tissue and location of catecholamines (for example degradation of catecholamines in the
synaptic cleft is mediated by COMT because MAO is a mitochondrial enzyme). The next catabolic steps in
the pathway involve alcohol dehydrogenase, aldehyde dehydrogenase and aldehyde reductase. The end
product of epinephrine and norepinephrine is vanillylmandelic acid (VMA) which is excreted in the urine.
Dopamine catabolism leads to the production of homovanillic acid (HVA).[9]

Function

Modality

Two catecholamines, norepinephrine and dopamine, act as neuromodulators in the central nervous system
and as hormones in the blood circulation. The catecholamine norepinephrine is a neuromodulator of the
peripheral sympathetic nervous system but is also present in the blood (mostly through "spillover" from the
synapses of the sympathetic system).

High catecholamine levels in blood are associated with stress, which can be induced from psychological
reactions or environmental stressors such as elevated sound levels, intense light, or low blood sugar levels.

Extremely high levels of catecholamines (also known as catecholamine toxicity) can occur in central
nervous system trauma due to stimulation or damage of nuclei in the brainstem, in particular, those nuclei
affecting the sympathetic nervous system. In emergency medicine, this occurrence is widely known as a
"catecholamine dump".

Extremely high levels of catecholamine can also be caused by neuroendocrine tumors in the adrenal
medulla, a treatable condition known as pheochromocytoma.

High levels of catecholamines can also be caused by monoamine oxidase A (MAO-A) deficiency, known
as Brunner syndrome. As MAO-A is one of the enzymes responsible for degradation of these
neurotransmitters, its deficiency increases the bioavailability of these neurotransmitters considerably. It
occurs in the absence of pheochromocytoma, neuroendocrine tumors, and carcinoid syndrome, but it looks
similar to carcinoid syndrome with symptoms such as facial flushing and aggression.[10][11]

Acute porphyria can cause elevated catecholamines.[12]

Effects

Catecholamines cause general physiological changes that prepare the body for physical activity (the fight-
or-flight response). Some typical effects are increases in heart rate, blood pressure, blood glucose levels,
and a general reaction of the sympathetic nervous system. Some drugs, like tolcapone (a central COMT-
inhibitor), raise the levels of all the catecholamines. Increased catecholamines may also cause an increased
respiratory rate (tachypnoea) in patients.[13]

Catecholamine is secreted into urine after being broken down, and its secretion level can be measured for
the diagnosis of illnesses associated with catecholamine levels in the body.[14] Urine testing for
catecholamine is used to detect pheochromocytoma.

Function in plants
 "They have been found in 44 plant families, but no essential metabolic function has been
established for them. They are precursors of benzo[c]phenanthridine alkaloids, which are the
active principal ingredients of many medicinal plant extracts. CAs have been implicated to
have a possible protective role against insect predators, injuries, and nitrogen detoxification.
They have been shown to promote plant tissue growth, somatic embryogenesis from in vitro
cultures, and flowering. CAs inhibit indole-3-acetic acid oxidation and enhance ethylene
biosynthesis. They have also been shown to enhance synergistically various effects of
gibberellins."[15]

Testing for catecholamines

Catecholamines are secreted by cells in tissues of different systems of the human body, mostly by the
nervous and the endocrine systems. The adrenal glands secrete certain catecholamines into the blood when
the person is physically or mentally stressed and this is usually a healthy physiological response.[16]
However, acute or chronic excess of circulating catecholamines can potentially increase blood pressure and
heart rate to very high levels and eventually provoke dangerous effects. Tests for fractionated plasma free
metanephrines or the urine metanephrines are used to confirm or exclude certain diseases when the doctor
identifies signs of hypertension and tachycardia that don't adequately respond to treatment.[17][18] Each of
the tests measure the amount of adrenaline and noradrenaline metabolites, respectively called metanephrine
and normetanephrine.

Blood tests are also done to analyze the amount of catecholamines present in the body.

Catecholamine tests are done to identify rare tumors at the adrenal gland or in the nervous system.
Catecholamine tests provide information relative to tumors such as: pheocromocytoma, paraganglioma, and
neuroblastoma.[19][20]

See also
Catechol-O-methyl transferase
Catecholaminergic polymorphic ventricular tachycardia
History of catecholamine research
Hormone
Julius Axelrod
Peptide hormone
Phenethylamines
Steroid hormone
Sympathomimetics
Vanillylmandelic acid

References
1. Fitzgerald, P. A. (2011). "Chapter 11. Adrenal Medulla and Paraganglia" (http://www.access
medicine.com/content.aspx?aID=8404198). In Gardner, D. G.; Shoback, D. (eds.).
Greenspan's Basic & Clinical Endocrinology (9th ed.). New York: McGraw-Hill. Retrieved
October 26, 2011.
 2. Purves, D.; Augustine, G. J.; Fitzpatrick, D.; Hall, W. C.; LaMantia, A. S.; McNamara, J. O.;
White, L. E., eds. (2008). Neuroscience (4th ed.). Sinauer Associates. pp. 137–138.
ISBN 978-0-87893-697-7.
3. "Catecholamines" (https://web.archive.org/web/20110716025522/http://myhealth.ucsd.edu/li
brary/healthguide/en-us/support/topic.asp?hwid=te7424). Health Library. San Diego, CA:
University of California. Archived from the original (http://myhealth.ucsd.edu/library/healthgui
de/en-us/support/topic.asp?hwid=te7424) on July 16, 2011.
4. Joh, T. H.; Hwang, O. (1987). "Dopamine Beta-Hydroxylase: Biochemistry and Molecular
Biology". Annals of the New York Academy of Sciences. 493: 342–350. doi:10.1111/j.1749-
6632.1987.tb27217.x (https://doi.org/10.1111%2Fj.1749-6632.1987.tb27217.x).
PMID 3473965 (https://pubmed.ncbi.nlm.nih.gov/3473965). S2CID 86229251 (https://api.se
manticscholar.org/CorpusID:86229251).
5. Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines".
Pharmacology & Therapeutics. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005 (htt
ps://doi.org/10.1016%2Fj.pharmthera.2009.11.005). PMID 19948186 (https://pubmed.ncbi.nl
m.nih.gov/19948186).
6. Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel
GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281.
doi:10.1016/j.tips.2005.03.007 (https://doi.org/10.1016%2Fj.tips.2005.03.007).
PMID 15860375 (https://pubmed.ncbi.nlm.nih.gov/15860375).
7. Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain
CYP2D". European Journal of Pharmacology. 724: 211–218.
doi:10.1016/j.ejphar.2013.12.025 (https://doi.org/10.1016%2Fj.ejphar.2013.12.025).
PMID 24374199 (https://pubmed.ncbi.nlm.nih.gov/24374199).
8. Kitahama, K.; Pearson, J.; Denoroy, L.; Kopp, N.; Ulrich, J.; Maeda, T.; Jouvet, M. (1985).
"Adrenergic neurons in human brain demonstrated by immunohistochemistry with
antibodies to phenylethanolamine-N-methyltransferase (PNMT): discovery of a new group in
the nucleus tractus solitarius". Neuroscience Letters. 53 (3): 303–308. doi:10.1016/0304-
3940(85)90555-5 (https://doi.org/10.1016%2F0304-3940%2885%2990555-5).
PMID 3885079 (https://pubmed.ncbi.nlm.nih.gov/3885079). S2CID 2578817 (https://api.sem
anticscholar.org/CorpusID:2578817).
9. Eisenhofer, G.; Kopin, I. J.; Goldstein, D. S. (2004). "Catecholamine metabolism: a
contemporary view with implications for physiology and medicine". Pharmacological
Reviews. 3 (56): 331–349. doi:10.1124/pr.56.3.1 (https://doi.org/10.1124%2Fpr.56.3.1).
PMID 15317907 (https://pubmed.ncbi.nlm.nih.gov/15317907). S2CID 12825309 (https://api.s
emanticscholar.org/CorpusID:12825309).
10. Manor, I.; Tyano, S.; Mel, E.; Eisenberg, J.; Bachner-Melman, R.; Kotler, M.; Ebstein, R. P.
(2002). "Family-Based and Association Studies of Monoamine Oxidase A and Attention
Deficit Hyperactivity Disorder (ADHD): Preferential Transmission of the Long Promoter-
Region Repeat and its Association with Impaired Performance on a Continuous
Performance Test (TOVA)" (https://doi.org/10.1038%2Fsj.mp.4001037). Molecular
Psychiatry. 7 (6): 626–632. doi:10.1038/sj.mp.4001037 (https://doi.org/10.1038%2Fsj.mp.40
01037). PMID 12140786 (https://pubmed.ncbi.nlm.nih.gov/12140786).
11. Brunner, H. G. (1996). "MAOA Deficiency and Abnormal Behaviour: Perspectives on an
Association". Ciba Foundation Symposium. Novartis Foundation Symposia. 194: 155–167.
doi:10.1002/9780470514825.ch9 (https://doi.org/10.1002%2F9780470514825.ch9).
ISBN 9780470514825. PMID 8862875 (https://pubmed.ncbi.nlm.nih.gov/8862875).
12. Stewart, M. F.; Croft, J.; Reed, P.; New, J. P. (2006). "Acute intermittent porphyria and
phaeochromocytoma: shared features" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994
495). Journal of Clinical Pathology. 60 (8): 935–936. doi:10.1136/jcp.2005.032722 (https://d
oi.org/10.1136%2Fjcp.2005.032722). PMC 1994495 (https://www.ncbi.nlm.nih.gov/pmc/artic
les/PMC1994495). PMID 17660335 (https://pubmed.ncbi.nlm.nih.gov/17660335).
13. Estes, Mary (2016). Health assessment and physical examination (2nd ed.). Melbourne:
Cengage. p. 143. ISBN 9780170354844.
14. "Catecholamines in Urine" (http://www.webmd.com/heart-disease/catecholamines-
14697#1). webmd.com. Retrieved 4 May 2017.
15. Kuklin, A. I.; Conger, B. V. (1995). "Catecholamines in Plants". Journal of Plant Growth
Regulation. 14 (2): 91–97. doi:10.1007/BF00203119 (https://doi.org/10.1007%2FBF002031
19). S2CID 41493767 (https://api.semanticscholar.org/CorpusID:41493767).
16. "Fight-or-flight response" (https://en.wikipedia.org/w/index.php?title=Fight-or-flight_response
&oldid=930948487), Wikipedia, 2019-12-16, retrieved 2019-12-24
17. "Plasma Free Metanephrines | Lab Tests Online" (https://labtestsonline.org/tests/plasma-free
-metanephrines). labtestsonline.org. Retrieved 2019-12-24.
18. "Urine Metanephrines | Lab Tests Online" (https://labtestsonline.org/tests/urine-metanephrin
es). labtestsonline.org. 6 December 2019. Retrieved 2019-12-24.
19. "Catecholamine Urine & Blood Tests" (https://www.webmd.com/heart-disease/catecholamin
es-test-facts). WebMD. Retrieved 2019-10-09.
20. "Catecholamines" (https://labtestsonline.org/tests/catecholamines). labtestsonline.org.
Retrieved 2019-10-09.

External links
Catecholamines (https://meshb.nlm.nih.gov/record/ui?name=Catecholamines) at the US
National Library of Medicine Medical Subject Headings (MeSH)

Retrieved from "https://en.wikipedia.org/w/index.php?title=Catecholamine&oldid=1084523607"

This page was last edited on 25 April 2022, at 00:56 (UTC).

Text is available under the Creative Commons Attribution-ShareAlike License 3.0;

additional terms may apply. By
using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the
Wikimedia Foundation, Inc., a non-profit organization.