Catecholamine

Structure

The structure of catecholamines is based on a bearing core catéchol in position 1 a possibly substituted side chain éthylamine. The core catéchol is characterized by presence of two groupings adjacent hydroxyls on a benzene core in position 3 and 4.

Figure 1. Chemical structure of the catécholamines

The dopamine is the simplest compound of the family of catecholamines, it consists of a core catéchol and a side chain éthylamine. Noradrenalin has in more one grouping hydroxyl on carbon β of the side chain, whereas the amine of adrenalin is substituted by a grouping methyl. The name of noradrenalin is derived from adrenalin, the NOR prefix, which means not radical , indicates the absence of radical methyl.

Metabolism of catecholamines

Biosynthesis

The way of biosynthesis of catecholamines begin with the Hydroxylation from an Amino-acid , the Tyrosine, collected in the extracellular medium by an active transport system. The hydroxylation of tyrosin in DOPED (dihydroxyphénylalanine) is catalyzed by an enzyme, tyrosin-3-hydroxylase, and constitutes the limiting stage of the synthesis of catecholamines. The activity of this enzyme is increased by the nerve impulses, via a phosphorylation dependant on AMPc, ions calcium or DAG (diacylglycérol), and is decreased by DOPED and noradrenalin. Tyrosin-3-hydroxylase uses a cofactor, the tétrahydrobioptérine (BH4) which is oxidized in dihydrobioptérine (BH2) then regenerated by the intervention of NADH (nicotinamide adénine dinucléotide reduced).

DOPED is décarboxylée in dopamine by a specific décarboxylase aromatic amino-acids using a cofactor, the phosphate of pyridoxal, activated form of the vitamin B₆. The dopamine is thus the first family member of catecholamines appearing in this way of biosynthesis. It can be hydroxylated out of noradrenalin by the dopamine-β-hydroxylase, which with is turn is methylated in adrenalin by phényléthanolamine-N-méthyltransférase (PNMT), an enzyme using the S-adénosyl methionine (SAM) as cofactor.

Catabolism

Catecholamines present in the Synapse are recaptées either by the nervous terminations, or by the cells gliales while utilizing an active transport depend on the ions sodium. The degradation of catecholamines utilizes two enzymes: catéchol-O-méthyltransférase (COMT) cytoplasmic and the monoamine oxydase (MAO) located on the external membrane of the Mitochondrie S. the catéchol-O-méthyltransférase is specific catecholamines, it carries out a methylation of one of the two groupings hydroxyl of the core catéchol, preferentially in position 3. The monoamine oxydase, which appears in the ways of catabolism of many compounds, catalyzes an oxydative desamination.

The action of the COMT on adrenalin and noradrenalin leads respectively to the métanephrine (MN) and the normétanéphrine (NMN). These two metabolites undergo the action of the MAO then and are transformed into vanillyl-mandelic acid (VMA). The action of the MAO enzymes and COMT on the dopamine leads to the acid homovanilic (HVA).

Secretion

Catecholamines are secreted by the Médullo-surrénale via the autonomous Nervous system in response in an emotional state, a stress, a pain, a Hypoxie, a Hypotension or a cold exposure. By their action on the cardiovascular sytème and the glucidic metabolism, they help the organization to face the emergencies. They can be increased under the effect of hypoglycemia insulinic.

The evaluation of the adrenal medulla rests mainly on the urinary determination of the acid vanillylmandelic (VMA), the métanéphrine and free catecholamines. In fact, the proportioning of these various parameters is useful especially for the diagnosis of the Phéochromocytome or the Neuroblastome.

Excretion

Catecholamines in a small proportion are excreted in the urine in a free state and in form combined with the Sulfate and the Glucuronate. Their excretion is dependant on the physical-activity of the patient: it increases during the intellectual and muscular efforts. As catecholamines of food origin are eliminated in combined form, it is preferable to proportion free catecholamines

== Functions biologiques==

Physiopathology

the Phéochromocytome S.

Method of proportioning

Principle

Urinary catecholamines are extracted beforehand on small columns from Silice grafted with an exchanging grouping from cations with pH 7.5, then they are éluées using an acid solution. The extract is then injected on a HPLC. The Chromatographie by HPLC consists in forming a pair of ions between catecholamines, cation with the pH of the mobile phase, and the octylsulfonate, anion agent of the fixed phase. The pairs of ions formed are non-polar and are chromatographiées on a C18 column. At the exit of the column, free catecholamines are analyzed by electrochemical detection with the potential of 650 mV, ensuring a good selectivity and an excellent sensitivity.

Test sample selection

To avoid wrongfully high results, it is necessary to recommend to the patient a rest of 24:00 (to avoid the muscular efforts, stress,…) as well as the removal of certain food (48h before the taking away, not to absorb a Vanilla, of The, of Banana, of Chocolate, of Nicotine) and some Médicaments which can interfere with the assay technique.

Noradrenalin and adrenalin are oxidized spontaneously with the oxygen dissolved in noradénochrome and adrénochrome. To avoid this self-oxidation, catalyzed by ions of heavy metals, the urine of the patient will be preserved in acid medium, or in the presence of a Chélateur (EDTA).

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