Urine homovanillic acid

MAO converts dopamine to DOPAC (3,4-dihydrox-yphenylacetic acid), which can be further metabolized by COMT to form homovanillic acid (HVA). HVA is the main product of dopamine metabolism and the principal dopamine metabolite in urine. Increased neuronal dopaminergic activity is associated with increases in plasma concentrations of DOPAC and HVA. COMT preferentially methylates dopamine at the 3 -hydroxyl position and utilizes S-adenosyl-L-methio-nine as a methyl group donor. COMT is expressed widely in the periphery and in glial cells. In PD, COMT has been targeted since it can convert l-DOPA to inactive 3-OMD (3-O-methyl-dopa). In the presence of an AADC inhibitor such as carbidopa, 3-OMD is the major metabolite of l-DOPA treatment. 

Metabolites of biogeiuc amines have also been analyzed by GC-ECD. For the simultaneous analysis of 5-hydroxyindole-3-acetic acid (5-HIAA), homovanillic acid (HVA) and m- and p-hydroxyphenylacetic acid (m-, p-HPAA), (metabolites of 5-HT, DA, and m- and p-tyramine acid respectively) in urine, a simple acidic extraction followed by derivatization with PFPA (derivatizes phenols) and hexafluoroisopropanol (deriva-tizes carboxylic acid groups) has been used (Davis et al., 1982 Baker et al., 1987). 

H12. Hoeldtke, R., Effect of aspirin on the assay of homovanilic acid in urine. Amer. J. Clin. Pathol. 57, 324-325 (1972). 

DISCUSSION. Caution should be exercised when interpreting chromatograms from a complex mixture of aromatic compounds in urine. This is especially true when excretion of the catechols is very high. When the derivatives of the compound extracted from urine of patients with phenylketonuria are prepared decomposition products of the large amounts of phenylpyruvic acid present give rise to peaks which interfere with and resemble HVA. When difficulties of this type are suspected, differential extraction of the urine can be performed. When alkaptonuria urine is extracted with dichloromethane, homovanillic acid is extracted preferentially, leaving the spurious compounds behind. 

Disposition in the Body. Rapidly absorbed from the small bowel after oral administration and widely distributed in the tissues less than 1% of a dose reaches the brain bioavailability about 33%. Extensively metabolised mainly by decarboxylation to dopamine, which is further metabolised, and also by methylation to 3-0-methyldopa which accumulates in the central nervous system most of a dose is decarboxylated by the gastric mucosa before entering the systemic circulation the decarboxylase activity is inhibited by carbidopa and benserazide. Dopamine is further metabolised to noradrenaline, 3-methoxytyramine, and to the two major excretory metabolites, 3,4-dihydroxyphenyl-acetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid, HVA). During prolonged therapy, the rate of levodopa metabolism appears to increase, possibly due to enzyme induction. About 70 to 80% of a dose is excreted in the urine in 24 hours. Of the material excreted in the urine, about 50% is DOPAC and HVA, 10% is dopamine, up to 30% is... 

Homoeopathic preparations, 51, 53 Homogeneous fluoro immunoassays, 154 Homogeneous immunoassays, 149 Homosulfaminum, 717 Homosulphanilamide, 716 Homovanillic acid, 322, 571, 702 Honvan, 975 Honvol, 975 Hordenine, 99, 661 Hordenine sulphate, 662 Hormoestrol, 657 Hormofemin, 537 Hormomed, 831 Hormonin, 830, 831 Horse plasma, phenylbutazone in, 96 Horse urine, anabolic steroids in, 95 examination of, 92 phenylbutazone in, 96 salicylic acid in, 96... 

Urine creatinine is used to adjust the values of urinary biological indicators for example, creatinine measurements are necessary for correction of vanilmandelic and homovanillic acids, which indicate neuroblastoma and pheochromocytoma, when excreted in urine in abnormally increased concentrations. Ratios of vanilmandelic and homovanillic acids to creatinine have been utilized as a diagnostic index of these diseases. 

The primary metabolites of dopamine are homovanillic acid and dihydroxyphenylacetic acid (75%) and norepinephrine (25%). The primary metabolites of epinephrine and norepinephrine are vanilylmandelic acid and 3-methoxy-4-hydroxy-phenethyleneglycol. Catecholamine metabolites and their conjugates are excreted in urine. 

An interesting finding about patients with neuroblastoma has been obtained by von Studnitz (S39). This author found in two of six such patients an increase in the urinary metabolites of DOPA besides dopamine and 3-methoxy-4-hydroxyphenylalanine, 3,4-dihydroxyphenylacetic (homoprotocatechuic) acid, which is not found in normal urine, occurred in the mine of these patients, whereas the elimination of homovanillic acid was increased. 

J.P. Buchet University Catholique, Belgium Homovanillic acid excretion in the urine of Mn exposed workers NS... 

Siqueira ME, Moraes EC. 1989. Homovanillic acid (HVA) and manganese in urine of workers exposed in a ferromanganese alloy plant. Med Lav 80 224-228. 

The DA or DOPAC may undergo methylation by catechol-O-methyltransferase (COMT), ultimately forming homovanillic acid (HVA), a metabolite excreted in urine. 

Another aspect of catecholaminergic turnover that has been studied is the measurement of the metabolites of dopamine (homovanillic acid, HVA) and noradrenaline (vanillylmandelic acid, VMA). Silbergeld and Chisholm (1976) reported that HVA was increased by 33% in brain and 265% in urine, and VMA was increased by 48% in brain and 216% in urine in mice given 5g Pb/1 (2625 ppm Pb) from birth. It is likely that increased urinary... 

Simultaneous Assay by Mass Fragmento-graphy of Vanillylmandelic Acid, Homovanillic Acid, and 3-Methoxy-4-hydroxyphenethylene Glycol in Cerebrospinal Fluid and Urine Biochem. Med. ll(l) 32-40 (1974) CA 82 53621c... 

Determination of Vanilmandelic Acid and Homovanillic Acid in Urine... 

Williams, C. M., Maury, S. and Kibler, R. F., Normal excretion of homovanillic acid in the urine of patients with Huntington s chorea, J. Neurochem. 6, 254 (1961). 

Fig. 2.3. Diagnostic flow-chart in the differentiation of defects of biogenic amine neurotransmitter metabolism. The correct differential diagnosis depends on the pattern of amines and their metabolites in either urine, CSF or plasma. represents increased values, [ represents lowered values. 5HIAA 5-hydroxyindoleacetic acid HVA homovanillic acid 5HT serotonin 30MD 3-0-methyldopa DOPAC dihydroxyphenylacetic acid 3MT 3-methoxytyramine NMN norme-tanephrine VMA vanillylmandelic acid DOPS dihydroxyphenylserine MHPG 3-methoxy-4-hydroxyphenylglycol Y yes N no. Plasma and CSF levels have not been analysed but they probably reflect those seen in urine. For interpretation of quantitative results see pathological values.

A hybrid FIA/HPLC system incorporating monolithic column chromatography was developed for the determination of six opiate alkaloids (morphine, pseudomorphine, codeine, oripavine, ethylmorphine, and thebaine) and four biogenic amines (vanilman-delic acid, serotonin, 5-hydroxyindole-3-acetic acid, and homovanillic acid) in human urine, using tris(2,2 -bipyridyl)ruthenium(III) and acidic potassium permanganate CL detection (Adcock et al., 2007). This hybrid system approaches the automation and separation efficiency of HPLC while maintaining the positive attributes of FIA, such as manifold versatility, speed of analysis, and portability. 

Gorden, E.K., Oliver, J., Black, K. and Kopin, I.J. (1974), Simultaneous assay by mass fragmentography of vanillylmandelic acid, homovanillic acid and 3-methoxy-4-hydroxy-phenethylene glycol in cerebrospinal fluid and urine. Biochem. Med., 11,32. 

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