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Catecholamine

OH

OH

Catechol 

dopamine

norepinephrine (noradrenaline)

A catecholamine (CA) i s a monoamine, an organic com-

pound that has a catechol (benzene with two hydroxyl side

groups) and a side-chain amine.

[1]

Catechol is a chemical, but a catechol may also be used

as the name of a substituent, where it represents a 1,2-

epinephrine (adrenaline)

dihydroxybenzene group.

Catecholamines are derived from the   amino acid

tyrosine.[2] Catecholamines are water-soluble and are

50%-bound to plasma proteins when they circulate in the

bloodstream.

In the  human body, the most abundant catecholamines

are   epinephrine   (adrenaline),   norepinephrine   (nora-

drenaline) and dopamine, all of which are produced from

phenylalanine   and tyrosine. Release of the  hormones

epinephrine and norepinephrine from the adrenal medullaof the   adrenal glands   is part of the   fight-or-flight re-

sponse.[3]

Tyrosine is created from phenylalanine by hydroxylation

by the enzyme   phenylalanine hydroxylase. Tyro-

sine is also ingested directly from dietary protein.

Catecholamine-secreting cells use several reactions to

convert 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 are catecholamine analogues.

1 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.

2 Production and degradation

1

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2   2 PRODUCTION AND DEGRADATION 

2.1 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  substantia nigra   and the   ventral

tegmental area. The similarly   melanin-pigmented cell

bodies of the locus ceruleus produce norepinephrine.

2.2 Synthesis

Dopamine is the first catecholamine synthesized from

DOPA. In turn, norepinephrine and epinephrine are de-

rived from further metabolic modification of dopamine.

The enzyme dopamine hydroxylase requires copper as a

cofactor (not shown) and DOPA decarboxylase requires

PLP (not shown). The rate limiting step in catecholamine

biosynthesis is hydroxylation of tyrosine.Human biosynthesis pathway for trace amines and

catecholamines[5]

L-Phenylalanine

L-Tyrosine

L-Dopa

Epinephrine

Phenethylamine p-Tyramine

Dopamine

Norepinephrine

N -Methylphenethylamine

N -Methyltyramine

 p-Octopamine

Synephrine

3-Methoxytyramine

AADC

AADC

AADC

PNMT

PNMT

PNMT

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3.2 Effects    3

PNMT

AAAH

AAAH

COMT

DBH

DBH

L-Phenylalanine is converted into   L-tyrosine by the

enzyme   Aromatic amino acid hydroxylase   (AAAH),

with molecular   oxygen   (O2) and   tetrahydrobiopterin

as cofactors.   L-Tyrosine is converted into   L-DOPA by

the enzyme AAAH 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 nore-

pinephrine by the enzyme   dopamine β-hydroxylase(DBH), with O2  and  L-ascorbic acid as cofactors. Nore-

pinephrine is converted into epinephrine by the enzyme

phenylethanolamine   N -methyltransferase   (PNMT) with

S -adenosyl-L-methionine as the cofactor.

Catecholamine synthesis is inhibited by alpha-methyl-p-

tyrosine (AMPT), which inhibits  tyrosine hydroxylase.

2.3 Degradation

Catecholamines have a half-life of a few minutes whencirculating 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 break-

ing down catecholamines and other monoamines.

3 Function

3.1 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 ascatecholamine toxicity) can occur in central nervous sys-

tem  trauma due to stimulation and/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 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. 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, neuroen-

docrine tumors, and carcinoid syndrome, but it looks sim-

ilar to carcinoid syndrome such as facial flushing and

aggression.[8][9]

3.2 Effects

Catecholamines cause general physiological changes that

prepare the body for physical activity (fight-or-flight re-

sponse). Some typical effects are increases in heart rate,

blood pressure, blood glucose levels, and a general reac-

tion of the sympathetic nervous system. Some drugs, like

tolcapone (a central COMT-inhibitor), raise the levels of

all the catecholamines.

3.3 Function in plants

“They have been found in 44 plant fam-

ilies, but no essential metabolic function has

been established for them. They are pre-

cursors 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 pro-

mote plant tissue growth, somatic embryogen-

esis from in vitro cultures, and flowering. CAs

inhibit indole-3-acetic acid oxidation and en-

hance  ethylene   biosynthesis. They have also

been shown to enhance synergistically variouseffects of gibberellins.”[10]

4 See also

•   Catechol-O-methyl transferase

•   Catecholaminergic polymorphic ventricular tachy-

cardia

•  History of catecholamine research

•   Hormone

•   Julius Axelrod

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4   6 EXTERNAL LINKS 

•   Peptide hormone

•   Phenethylamines

•   Steroid hormone

•   Sympathomimetics

•   Vanillylmandelic acid

5 References

[1] Fitzgerald, P. A. (2011). “Chapter 11. Adrenal Medulla

and Paraganglia”. In Gardner, D. G.; Shoback, D.

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., ed.

(2008).   Neuroscience  (4th ed.). Sinauer Associates. pp.

137–8. ISBN 978-0-87893-697-7.

[3]  “Catecholamines”.  Health Library. San Diego: University

of California.

[4] Joh, T. H.; Hwang, O. (1987). “Dopamine Beta-

Hydroxylase: Biochemistry and Molecular Biology”.  An-

nals of the New York Academy of Sciences   493: 342–

350.   doi:10.1111/j.1749-6632.1987.tb27217.x.   PMID

3473965.

[5]   [6][7]

[6] Broadley KJ (March 2010). “The vascular effects of

trace amines and amphetamines”.   Pharmacol. Ther.  125

(3): 363–375.   doi:10.1016/j.pharmthera.2009.11.005.

PMID 19948186.

[7] Lindemann L, Hoener MC (May 2005). “A renais-

sance in trace amines inspired by a novel GPCR fam-

ily”.   Trends Pharmacol. Sci.   26   (5): 274–281.

doi:10.1016/j.tips.2005.03.007. PMID 15860375.

[8] 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)".  Molecular 

Psychiatry  7  (6): 626–632.   doi:10.1038/sj.mp.4001037.

PMID 12140786.

[9] Brunner, H. G. (1996). “MAOA Deficiency and Abnor-

mal Behaviour: Perspectives on an Association”.   Ciba

Foundation Symposium  194: 155–164; discussion 164–

167. PMID 8862875.

[10] Kuklin, A. I.; Conger, B. V. (1995). “Catecholamines inPlants”.  Journal of Plant Growth Regulation  14   (2): 91–

97. doi:10.1007/BF00203119.

6 External links

•   Catecholamines   at the US National Library of

Medicine Medical Subject Headings (MeSH)

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