4- Hydroxymandelic acid

The synthesis and metabolism of trace amines and monoamine neurotransmitters largely overlap [1]. The trace amines PEA, TYR and TRP are synthesized in neurons by decarboxylation of precursor amino acids through the enzyme aromatic amino acid decarboxylase (AADC). OCT is derived from TYR. by involvement of the enzyme dopamine (3-hydroxylase (Fig. 1 DBH). The catabolism of trace amines occurs in both glia and neurons and is predominantly mediated by monoamine oxidases (MAO-A and -B). While TYR., TRP and OCT show approximately equal affinities toward MAO-A and MAO-B, PEA serves as preferred substrate for MAO-B. The metabolites phenylacetic acid (PEA), hydroxyphenylacetic acid (TYR.), hydroxymandelic acid (OCT), and indole-3-acetic (TRP) are believed to be pharmacologically inactive. 

Fio. 36. Vloi t Hoff plou of the retention bctors of aromatic acids in reversed-phase chromatography using octadecyl silica as the stationaiy phase and neat aqueous 30 taM NaHiPO buffer (pH 2.0) (open symbols), or the same buffer containing 696 (v/v) of aceloni ti (closed symbols) as the eluent. Column S imSpherisorbODS, 230 x 4.6 mm. Eluites 3.4xlihydroxymandelic acid (O. ) 4 hydroxymandelic acid ( , ) 4-hydroxyphenylacetic acid (7. ) 3,4-dihydroxyphenylacetic acid (A, A). Reprinted with permission from Me-lander tt at. U77). 

More complicated procedures, involving more extensive chemical changes of the acids under analysis, have been developed for special purposes. As an example, the determination of 3-methoxy-4-hydroxymandellic acid in urine, described by Dekirmenjian and... 

C8H8N4 3-amino-3-phenyl-1,2,4-triazole 4922-98-9 25 00 1.2451 2 13497 C8H804 DL-4-hydroxymandelic acid 7198-10-9 25.00 1.2537 2... 

The reaction of phenols 287 with glycolic acid (288) in the presence of DBU gave hydroxymandelic acids 289 in good yields (81JAP(K)68641). 

Mcthylation by COMT occurs almost exclusively on the mrhi-hydroxyl group of the catechol, regardless of whether ihe catechol is NE, epinephrine, or one of the metabolic products. For example, the action of COMT on NE and epinephrine gives normetanephrine and metanephrine. respectively. A converging pattern of NE metabolism of NE and epinephrine in which 3-mcthoxy-4-hydroxymandelic acid and T-methoxy-d-hydroxyphcnylethylcnc glycol are common end products thus occurs, regardle.ss of whether the first metabolic step is oxidation by MAO or mcthylation by COMT. 

Kairisto V, Koskinen P, Mattila K> Puilckonen J, Virtanen A, Kantola I, Irjala K. Reference intervals for 24-h urinary normetanephrine, metanephrine, and 3-methoxy-4-hydroxymandelic acid in hypertensive patients. Clin Chem 1992 38 416-20. 

Pisano J, Grout R, Abraham D. Determination of 3-methoxy-4-hydroxymandelic acid in urine. Clin Chim Acta 1962 7 285-9. 

The hydroxyalkylation of phenols with chiral glyoxylates, followed by hydrolysis, gives regioselectively 2-hydroxymandelic acids with high enantioselectivity (eqnation 28). The crystal-structure determination of the titanium phenoxide complex shows evidence for chelation-controlled reaction giving the observed high enantioselectivities . ... 

Hydroxylamines—see A-Arylbydroxylamines Hydroxylation 1167 Hydroxyl radicals 1098 2-Hydroxymandelic acids, formation of 623... 

The transmitter that is taken up into the neuron and liberated into the intracellular fluid can then either be recycled into vesicular storage granules or metabolized by intracellular enzymes. The two enzymes that are of major importance for the catabolism of aromatic monoamines are monoamine oxidase, of which there may be two or more isozymes, and catechol-O-meth-yltransferase. In neurons, monoamine oxidase is associated with mitochondria, whereas catechol-O-methyltransferase is associated with the soluble cytoplasmic fraction. Both monoamine oxidase and catechol-O-methyltransferase can act on monoamines sequentially to form a variety of metabolic products. These have been identified by radioisotopic and chromatographic experiments. The major metabolites of the aromatic monoamines have been identified 3-methoxy-4-hydroxyphenylethylene glycol and 3-methoxy-4-hydroxymandelic acid (vanylmandelic acid) for norepinephrine and epinephrine 3,4-dihydroxyphenylacetic acid and 3-meth-... 

The base usually used for the condensation between phenols and glyoxylic acid is sodium hydroxide. The reaction is selective for the para position, but the 2- and 4-hydroxymandelic acids produced are more reactive than the phenols, and the consecutive reaction is the formation of dimandelic acid (Fig. 2). 

Axelrod has shown that, in man, circulating adrenaline and noradrenaline are metabolized predominantly by catechol 0-methyltransferase, approximately 70 per cent of an administered dose being inactivated by 0-methyla-tion and 20 per cent by deamination. Generally similar results were obtained in studies on other mammals. The principal urinary metabolite of the catechol amines is 3-methoxy-4-hydroxymandelic acid. 

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