Studies on urinary phenolic acid metabolites of norepinephrine
Creators: name: McMillan, Armand
Publisher: name: University of Utah
Year: 2012
Subjects: Noradrenaline - Metabolism

description: 1.  The literature concerning norepinephrine has been reviewed briefly in respect to the discovery, the biosynthesis and the metabolism of the compound.  Special attention was paid to the degradation of the catechol amines by amine oxidase.  2.  Gardner and Hibbert's synthesis of 3-methoxy-4-hydroxymandelic acid from vanillin via the cyanohydrin and the ester has been considerably improved.  The method was adapted with fair success to the preparation of 3, 4-dihydroxymandelic acid; no satisfactory synthesis has been reported for this compound.  3.  Synthetic 3-methoxy-4-hydroxymandelic acid was resolved by means of its cinchonine salts; the enantiomorphs were regenerated from the crude salts and characterized.  A small amount of pure cinchonine 3-methoxy-4-hydroxy-(-)-mandelate was prepared.  4.  The configuration of the isomers of 3-methoxy-4 hydroxymandelic acid was established by enzymic hydrolysis of the DL-amide with L-leucine aminopeptidase.  3-Methosy-4-Hydroxoy-D (-)-mandelamide was obtained in pure form by this process and was characterized.  The isomers of the acid were found to be 3-methoxoy-4-hydroxy-L (+)-mandelic acid and 3-methosy-4hydroxy-D (1)-mandelic acid.  5.  3-Methoxy-4-hydroxymandelic acid has been shown to be a metabolite of 3, 4-dihydroxymandelic acid, norepinephrine and possible, epinephrine.  The catechol amines are first converted to 3, 4-dihydroxymandelaldehyde by the action of amine oxidase.  The aldehyde is further oxidized to 3, 4-dihydroymandelic acid.   The acid is then methylated and decarbosylated to give respectively, 3-methoxoy-4-hydroxyandelic acid and protocatechuic acid.  These compounds, with the exception of the aldehyde and protocatechuic acid, were ingested and the phenolic acids metabolites were extracted from the resulting urines and determined by paper chromatography.  Further evidence for the metabolic path was provided by the detection, isolation and characterization of 3-methoxy-4-hydroxymandelic acid from the urine of patients with phechromocytoma and by the finding of increased amounts of urinary 3-methoxy-4-hydroxymandelic acid after the parenteral injection of nerepinephrine.  6.  A clinical procedure for the diagnosis of pheochromocytoma has been developed.  It is based on the fact that patients in this condition excrete increased amounts of 3-metoxy-4-hydroxymandelic acid.  The increase output of the compound is observed readily when two-dimensional chromatograms of phenolic acids concentrates from pathological urines are compared to similar chromatograms prepared from equivalent amount (1 mg. of urinary creatinine) of normal urine.  The greater stability of 3-methoxy-4-hydroxymandelic acid, as compared to that of the catechol amines, eliminates the special precautions and involved techniques required in the determination of the latter compounds.  7.  In the course of testing the ?-glucuronidase used for the detection of conjugated metabolites, it was shown that ingested vanillic acid is excreted in human urine s the free acid, as the glucuronide and as the substituted hippuric acid.  Vanillic acid and its glucuronide were present in equal amounts; the quantity of vanilloyliglycine was not determined.