Inhibition of histidine, decarboxylation in vivo by 2-hydroxy-5-carbomethoxybenzyloxyamine, a new, potent inhibitor of histidine decarboxylase.
Measurements of the rate of expiration of 14CO2 were carried out after the injection into rats of 14C-histidine labeled in the carboxyl group (C-His) or in the imidazole ring (R-His).  Intraperitoneal administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, a new potent inhibitor of histidine decarboxylase, reduced the rate of 14CO2 production from C-His and R-His in a dose-dependent manner.  The metabolism of C-His was more affected than that of R-His.  The inhibitor had no effect on the production of 14CO2 from 14C-urocanic acid, 14C-dopa or 14C-glutamic acid.  Rats given 2-hydroxy-5-carbomethoxybenzyloxyamine (100 mg/kg) by the intraperitoneal route had diminished histidine decarboxylase activity of stomach (96 percent decrease), but did not have any change in the activities of histidase, urocanase or histidine-pyruvate aminotransferase of liver.  After the administration of histidine (500 mg/kg), the level of this amino acid in serum remained elevated somewhat longer in inhibitor-treated animals than in the controls.  The temporary rise in serum histidine relative to controls that were also histidine-loaded is considered to reflect the decreased rate of uptake of histidine into the tissues, and also a decreased rate of decarboxylation of histidine in certain organs.  After the administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, the decreased rate of 14CO2 production from injected R-His and the delayed disappearance of histidine from the serum after a histidine load were considered to reflect mainly the decreased rate of histidine uptake into the tissues.  The decreased rate of formation of 14CO obtained with C-His appeared to result from inhibition of both uptake and decarboxylation of histidine.
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D006639:Histidine / Q000097:blood; D006638:Histidine Ammonia-Lyase / Q000378:metabolism; D006898:Hydroxylamines / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D008297:Male; D008750:Methyldopa / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D011773:Pyruvates; D051381:Rats; D013270:Stomach / Q000201:enzymology; D000637:Transaminases / Q000378:metabolism; D014559:Urocanate Hydratase / Q000378:metabolism
D005971:Glutamates; D006898:Hydroxylamines; D010636:Phenols; D011773:Pyruvates; D002245:Carbon Dioxide; D006639:Histidine; D008750:Methyldopa; D004295:Dihydroxyphenylalanine; D000637:Transaminases; D002262:Carboxy-Lyases; D014559:Urocanate Hydratase; D006638:Histidine Ammonia-Lyase