Acatecholamine (/ˌkætəˈkoʊləmiːn/; abbreviatedCA), most typically a3,4-dihydroxyphenethylamine, is amonoamine neurotransmitter, anorganic compound that has acatechol (benzene with twohydroxyl side groups next to each other) and aside-chainamine.[1]
Catechol can be either a free molecule or asubstituent of a larger molecule, where it represents a 1,2-dihydroxybenzene group.
Catecholamines are derived from theamino acidtyrosine, which is derived from dietary sources as well as synthesis fromphenylalanine.[2] Catecholamines are water-soluble and are 50% bound to plasma proteins in circulation.
Included among catecholamines areepinephrine (adrenaline),norepinephrine (noradrenaline), anddopamine. Release of thehormones epinephrine and norepinephrine from theadrenal medulla of theadrenal glands is part of thefight-or-flight response.[3]
Tyrosine is created from phenylalanine byhydroxylation by the enzymephenylalanine hydroxylase. Tyrosine is also ingested directly from dietary protein. Catecholamine-secreting cells use several reactions to convert tyrosine serially toL-DOPA and then to dopamine. Depending on the cell type, dopamine may be further converted to norepinephrine or even further converted to epinephrine.[4]
Variousstimulant drugs (such as a number ofsubstituted amphetamines) are catecholamine analogues.
Catecholamines have the distinct structure of abenzene ring with twohydroxyl groups, an intermediateethyl chain, and a terminalamine group. Phenylethanolamines such as norepinephrine have a hydroxyl group on the ethyl chain.[citation needed]
  L-Phenylalanine is converted intoL-tyrosine by anaromatic amino acid hydroxylase (AAAH) enzyme (phenylalanine 4-hydroxylase), with molecularoxygen (O2) andtetrahydrobiopterin ascofactors.L-Tyrosine is converted intoL-DOPA by another AAAH enzyme (tyrosine 3-hydroxylase) withtetrahydrobiopterin, O2, andferrousiron (Fe2+) as cofactors.L-DOPA is converted into dopamine by the enzymearomaticL-amino acid decarboxylase (AADC), withpyridoxal phosphate as the cofactor. Dopamine itself is also used as precursor in the synthesis of the neurotransmittersnorepinephrine andepinephrine. Dopamine is converted into norepinephrine by the enzymedopamine β-hydroxylase (DBH), with O2 andL-ascorbic acid as cofactors. Norepinephrine is converted into epinephrine by the enzymephenylethanolamineN-methyltransferase (PNMT) withS-adenosyl-L-methionine as the cofactor. |
Catecholamines are produced mainly by thechromaffin cells of theadrenal medulla and thepostganglionic fibers of thesympathetic nervous system.Dopamine, which acts as aneurotransmitter in thecentral nervous system, is largely produced in neuronal cell bodies in two areas of the brainstem: theventral tegmental area and thesubstantia nigra, the latter of which containsneuromelanin-pigmented neurons. The similarly neuromelanin-pigmented cell bodies of thelocus coeruleus producenorepinephrine.Epinephrine is produced in small groups of neurons in the human brain which express its synthesizing enzyme,phenylethanolamineN-methyltransferase;[8] these neurons project from a nucleus that is adjacent (ventrolateral) to thearea postrema and from a nucleus in the dorsal region of thesolitary tract.[8]
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 acofactor (not shown in the diagram) and DOPA decarboxylase requiresPLP (not shown in the diagram). The rate limiting step in catecholamine biosynthesis through the predominant metabolic pathway is the hydroxylation ofL-tyrosine toL-DOPA.[9]
Catecholamine synthesis is inhibited by alpha-methyl-p-tyrosine (AMPT), which inhibitstyrosine hydroxylase.[citation needed]
The amino acidsphenylalanine andtyrosine are precursors for catecholamines. Both amino acids are found in high concentrations inblood plasma and the brain. In mammals, tyrosine can be formed from dietary phenylalanine by the enzymephenylalanine hydroxylase, found in large amounts in the liver. Insufficient amounts of phenylalanine hydroxylase result inphenylketonuria, a metabolic disorder that leads to intellectual deficits unless treated by dietary manipulation.[citation needed] Catecholamine synthesis is usually considered to begin with tyrosine. The enzymetyrosine hydroxylase (TH) converts the amino acidL-tyrosine into 3,4-dihydroxyphenylalanine (L-DOPA). The hydroxylation ofL-tyrosine by TH results in the formation of the DA precursorL-DOPA, which is metabolized byaromaticL-amino acid decarboxylase (AADC; see Cooper et al., 2002[citation needed]) to the transmitter dopamine. This step occurs so rapidly that it is difficult to measureL-DOPA in the brain without first inhibiting AADC.[citation needed] Inneurons that use DA as the transmitter, the decarboxylation ofL-DOPA to dopamine is the final step in formation of the transmitter; however, in those neurons usingnorepinephrine (noradrenaline) orepinephrine (adrenaline) as transmitters, the enzymedopamine β-hydroxylase (DBH), which converts dopamine to yield norepinephrine, is also present. In still other neurons in which epinephrine is the transmitter, a third enzymephenylethanolamineN-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]
Catecholamines have a half-life of a few minutes when circulating in the blood. They can be degraded either by methylation bycatechol-O-methyltransferases (COMT) or by deamination bymonoamine 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 usesMg2+ as a cofactor while MAO usesFAD. 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 involvealcohol dehydrogenase,aldehyde dehydrogenase andaldehyde reductase. The end product of epinephrine and norepinephrine isvanillylmandelic acid (VMA) which is excreted in theurine. Dopamine catabolism leads to the production ofhomovanillic acid (HVA).[10]
Two catecholamines,norepinephrine anddopamine, act asneuromodulators in thecentral nervous system and as hormones in the blood circulation. The catecholaminenorepinephrine is a neuromodulator of the peripheral sympathetic nervous system but is also present in the blood (mostly through "spillover" from thesynapses of the sympathetic system).[citation needed]
High catecholamine levels in blood are associated withstress, which can be induced from psychological reactions or environmental stressors such aselevated sound levels,intense light, orlow blood sugar levels.[11]
Extremely high levels of catecholamines (also known as catecholamine toxicity) can occur incentral nervous system trauma due to stimulation or damage ofnuclei in thebrainstem, in particular, those nuclei affecting thesympathetic nervous system. Inemergency medicine, this occurrence is widely known as a "catecholamine dump".
Extremely high levels of catecholamine can also be caused byneuroendocrine tumors in theadrenal medulla, a treatable condition known aspheochromocytoma.
High levels of catecholamines can also be caused bymonoamine oxidase A (MAO-A) deficiency, known asBrunner syndrome. As MAO-A is one of the enzymes responsible for degradation of these neurotransmitters, its deficiency increases thebioavailability of these neurotransmitters considerably. It occurs in the absence ofpheochromocytoma,neuroendocrine tumors, andcarcinoid syndrome, but it looks similar to carcinoid syndrome with symptoms such as facial flushing and aggression.[12][13]
Acuteporphyria can cause elevated catecholamines.[14]
Degeneration of thelocus coeruleus and reduced production of norepinephrine during aging are under preliminary research as possible factors in the pathogenesis ofAlzheimer's disease.[15]
Catecholamines cause general physiological changes that prepare the body for physical activity (thefight-or-flight response). Some typical effects are increases inheart rate,blood pressure,blood glucose levels, and a general reaction of thesympathetic nervous system.[citation needed] Some drugs, liketolcapone (a centralCOMT-inhibitor), raise the levels of all the catecholamines. Increased catecholamines may also cause an increased respiratory rate (tachypnoea) in patients.[16]
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.[17]Urine testing for catecholamine is used to detectpheochromocytoma.
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They have been found in 44 plant families, but no essential metabolic function has been established for them. They are precursors of benzo[c]phenanthridinealkaloids, which are the active principal ingredients of manymedicinal 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, somaticembryogenesis from in vitro cultures, and flowering. CAs inhibitindole-3-acetic acid oxidation and enhanceethylene biosynthesis. They have also been shown to enhance synergistically various effects ofgibberellins.[18]
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 freemetanephrines or the urine metanephrines are used to confirm or exclude certain diseases when the doctor identifies signs ofhypertension andtachycardia that don't adequately respond to treatment.[19][20] Each of the tests measure the amount of adrenaline and noradrenaline metabolites, respectively calledmetanephrine andnormetanephrine.
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.[21][22]
