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Although the metabolism of serotonin (5-HT) has been investigated intensively, the metabolic fate of this amine has not been defined completely. In ma.n, the major metabolic route for 5-HT is oxidative deamination to the intermediate aldehyde and then oxidation to 5-hydroxyindoleacetic acid Evidence for a reductive pathway of 5-HT metabolism to the corresponding alcohol has recently been demonstrated in animals. Thus, Kveder et a1 found that 5-hydroxytryptophol (5-HTOH) was formed from 5-HT by rat liver slices and that 5-HTOH-0-glucuronide was a major 5-HT metabolite in rat urine( 2 ) .Bartholini, Pletscher, and Bruderer showed the formation of 5-HTOH from 5-HT during the incubation of isolated rabbit platelets with reserpine ( 3 ) . Subsequently, Feldstein and Wong detected both the aldehyde and the alcohol derivatives of 5-HT in rat liver homogenates incubated with 5-HT-C1* ( 4 ) . (5-HIAA) ( 1). This communication reports the isolation and identification of free 5-HTOH and 5-HTOH liberated from its glucuronide and sulfate conjugates in human urine and documents the in vivo conversion of 5-HT-C14 to 5-HTOH-C14 in man.Extraction of free and enzymaticallyreleased 5-hydroxytryp.tophoE. Aliquots ( 7 5 ml) of 24-hour urine collections from patients with carcinoid tumors were adjusted to pH 11 with sodium hydroxide. Solid barium chloride was added to precipitate inorganic phosphates and sulfates which interfere with subsequent sulfatase hydrolysis. The samples were centrifuged to sediment the barium precipitates. The supernatant urine was then filtered and adjusted to pH 7. Separate 20 ml aliquots of the urine were saturated with sodium chloride and the free 5-HTOH was extracted with two volumes of ether. The ether extracts were then washed with 3 ml of 0.5 h4 phosphate buffer, pH 7, to remove traces of 5-HTAA.The ether extracted urine was pooled and incubated with 15,000 units of bacterial at Harvard Libraries on June 25, 2015 ebm.sagepub.com Downloaded from

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