Urine normetanephrine

Degradation of catecholamines The catecholamines are inacti vated by oxidative deamination catalyzed by monoamine oxidase (MAO), and by O-methylation carried out by catechol-O-methyl-transferase (COMT, Figure 21.15). The two reactions can occur in either order. The aldehyde products of the MAO reaction are axi dized to the corresponding acids. The metabolic products of these reactions are excreted in the urine as vanillylmandelic acid, metanephrine, and normetanephrine. 

Fales and Pisano (30) were the first to describe the gas chromatographic analysis of amphetamine. They used 4% SE-30 in a silanized glass column and an argon ionization detector for the separation of (3-phenethylamine, amphetamine, norephedrine, eph drine, histamine, tyramine, dimethyltriptamine, tryptamine, 5-methoxytryptamine, benzylamine, N-methylbenzylamine, octopamine, synephrine, normetanephrine, serotonin, N-acetyltryptamine, find melatonin. The method was also used for the analysis of amphetamine extracted from urine. 

Potential fates of recaptured norepinephrine Once norepinephrine reenters the cytoplasm of the adrenergic neuron it may be taken up into adrenergic vesicles via the amine transporter system and be sequestered for release by another action potential or persist in a protected pool. Alternatively, norepinephrine can be oxidized by monoamine oxidase (MAO) present in neuronal mitochondria. The inactive products of norepinephrine metabolism are excreted in the urine as vanillylmandelic acid (VMA), metanephrine and normetanephrine. 

Four catecholamines have been found in increased amounts in the urine after injury (W2), metanephrine, normetanephrine, iV-methyl-metanephrine, and 3-methoxytyramine. The JV-methylmetanephrine probably indicates an increased production of epinephrine (Cll). The increase in norepinephrine production is relatively greater than that of epinephrine, suggesting an active release of hormone from sympathetic nerve tissue as well as from the adrenal medulla. 

Additional markers of catecholamine overproduction have been employed to improve the biochemical detection of neuroblastomas. Free dopamine may be abnormal in urine from neuroblastoma patients with VMA and HVA excretion. Combined testing for VMA, HVA, and dopamine may therefore improve tumor detection, and in 1993 an international consensus report on neuroblastoma diagnosis added dopamine to the Hst of acceptable measurements to document the adrenergic nature of the tumor. Plasma measurements of dopamine and L-dopa, the amino acid precursor of dopamine, may also have clinical value and allow the alternate use of plasma. Measurement of methylated metabolites, especially normetanephrine, has also been explored. When urinary normetanephrine, metanephrine, methoxytyra-mine, dopamine, norepinephrine, VMA, and HVA were measured, clinical sensitivity for detection of neuroblastomas was 97% to 100% when results of normetanephrine testing were coupled either with VMA in the infants or with HVA in children greater than age 1. Even with an extended panel of catecholamines and metabolite measurements, a low incidence of nonsecreting tumors continues to be identified and should be considered in the interpretation of a negative test result. 

In contrast to the catecholamines, measurements of urinary metanephrines and VMA are still based in some routine laboratories on the early spectrophotometric assays developed by Pisano, Crout, and others in the late 1950s and early 1960s. Despite subsequent development of a variety of preanalytical cleanup and extraction procedures, these assays remain susceptible to analytical interference. They are also restricted to measurements in urine. Another limitation for spectrophotometric or fiuorometric assays of urinary metanephrines is that these methods do not allow separate (fractionated) measurements of normetanephrine and metanephrine. 

Normetanephrine andmetanephrine are metabolic products of norepinephrine and epinephrine, respectively, and are formed by the action of catechol-0-methyltransferase without deamination. As a result of active neuronal reuptake and deamination of norepinephrine, normetanephrine normally represents <5% of the total norepinephrine excretion products in urine. Metanephrine, however, even with its lower urinary concentration relative to normetanephrine, represents a major excretion product of epinephrine. The metanephrines are excreted in both conjugated and unconjugated forms. Unlike the catecholamines, total metanephrine excretion is not significantly influenced by diet. As a result, the total metanephrines are routinely measured after acid hydrolysis or sulfatase pretreatment. 

Buu NT, Angers M, Chevalier D, Kuchel O. A new method for the simultaneous analysis of free and sulfoconjugated normetanephrine, metanephrine, and 3-methoxytyramine in human urine by HPLC with electrochemical detection. J Lab Clin Med 1984 104 425-32. 

Pisano J. A simple analysis of normetanephrine and metanephrine in urine. Clin Chim Acta 1960 5 406-14. 

Smith E. Metanephrine and normetanephrine in human urine method and results. J Lab Clin Med 1962 60 212-23. 

Taniguchi K, Kakimoto Y, Armstrong M. Quantitative determination of metanephrine and normetanephrine in urine. J Lab Clin Med 1964 64 469-84. 

Z. Kahane and P. Vetergaard, Column chromatographic separation and fluorometric estimation of metanephrine and normetanephrine in urine, Clin. Chim. Acta, 25, 453 58 (1969). 

L.B. Biglow and H. Weil-Malherbe, A simplified method for the differential estimation of metanephrine and normetanephrine in urine. Anal. Biochem., 26, 92-103 (1968). 

J. Jouve, N. Mariotte, C. Sureau and H.P. Muh, High-performance liquid chromatography with electrochemical detection for the simultaneous determination of the methoxy lated amines, normetanephrine, metanephrine and 3-methoxytyramine in urine, J. Chromatogr, llA, 53-62 (1983). 

D.K. Crockett, E.L. Frank and W.L. Roberts, Rapid analysis of metanephrine and normetanephrine in urine by gas chromatography-mass spectrometry, Clin. Chem., 48, 332-337 (2002). 

Clarke, D. D., and Gitlow, S. E. Gas-Liquid Chromatographic Method for the Separation and Quantitation of Normetanephrine and Metanephrine in Human Urine... 

Free Normetanephrine and Meta-nephrine in Urine by Selected Ion Monitoring... 

Dopamine was produced by incubating liver microsomes of rabbits with p- and m-tyramine, noradrenaline, and normetanephrine by incubation with w-octopamine, and adrenaline by incubation with p- and w-methyloctop-amine/" The injection of labelled tyramine as well as of labelled octopamine in the intact animal (rat) caused the appearance of labelled noradrenaline and normetanephrine in the urine/ As tyramine is also hydroxylated to octopamine, it is possible that the production of noradrenaline from tyramine not only takes place via its conversion to dopamine, but also via its conversion to octopamine. The possibility that octopamine is produced by the hydroxylation of tyrosine to hydroxyphenylserine with ensuing decarboxylation is under discussion. The production of noradrenaline from 3,4-dihydroxyphenylserine, 192-201) amino-acid so far not discovered in the mammal could be demonstrated both in organ extracts and in intact animals. Finally, a transamination of 3-hydroxy- or 3,4-dihydroxyphenylpyruvate to the corresponding amino-acids (m-tyrosin, dopa), and their decarboxylation to m-tyramine and dopamine was observed in intact animals (cats). For the time being it is impossible to determine the importance of the means of formation of catecholamines which have been referred to here. Of the above-mentioned precursor substances, p- and m-tyramine,( octopamine, ... 

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