Catecholamine

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Catecholamines
Epinephrine
(Adrenaline)

Norepinephrine (Noradrenaline)

Dopamine
Catechol

A catecholamine (

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] Catecholamines are water-soluble and are 50% bound to plasma proteins in circulation.

Included among catecholamines are

epinephrine and norepinephrine from the adrenal medulla of the adrenal 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 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.

Structure

Catecholamines have the distinct structure of a

hydroxyl groups, an intermediate ethyl chain, and a terminal amine group. Phenylethanolamines such as norepinephrine have a hydroxyl group on the ethyl chain.[citation needed
]

Production and degradation

Biosynthetic pathways for catecholamines and trace amines in the human brain[5][6][7]
The image above contains clickable links
In humans, catecholamines (shown in yellow) are derived from the
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

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.[citation needed]

Catecholamine synthesis is inhibited by alpha-methyl-p-tyrosine (

AMPT), which inhibits tyrosine hydroxylase.[citation needed
]

The amino acids

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).[citation needed
]

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.

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,

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).[citation needed
]

High catecholamine levels in blood are associated with

elevated sound levels, intense light, or low blood sugar levels.[citation needed
]

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

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.

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

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.[citation needed] 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.[16][17] 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: pheochromocytoma, paraganglioma, and neuroblastoma.[18][19]

See also

References

  1. ^ Fitzgerald, P. A. (2011). "Chapter 11. Adrenal Medulla and Paraganglia". In Gardner, D. G.; Shoback, D. (eds.). Greenspan's Basic & Clinical Endocrinology (9th ed.). New York: McGraw-Hill. Retrieved October 26, 2011.
  2. ISBN 978-0-87893-697-7
    .
  3. ^ "Catecholamines". Health Library. San Diego, CA: University of California. Archived from the original on July 16, 2011.
  4. S2CID 86229251
    .
  5. PMID 19948186
    .
  6. PMID 15860375
    .
  7. PMID 24374199
    .
  8. ^
    S2CID 2578817
    .
  9. S2CID 12825309
    .
  10. PMID 12140786
    .
  11. PMID 8862875
    .
  12. PMID 17660335
    .
  13. ISBN 978-0-17-035484-4
    .
  14. ^ "Catecholamines in Urine". webmd.com. Retrieved 4 May 2017.
  15. S2CID 41493767
    .
  16. ^ "Plasma Free Metanephrines | Lab Tests Online". labtestsonline.org. Retrieved 2019-12-24.
  17. ^ "Urine Metanephrines | Lab Tests Online". labtestsonline.org. 6 December 2019. Retrieved 2019-12-24.
  18. ^ "Catecholamine Urine & Blood Tests". WebMD. Retrieved 2019-10-09.
  19. ^ "Catecholamines". labtestsonline.org. Retrieved 2019-10-09.

External links

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