Human spleen dihydroorotate dehydrogenase: a study of inhibition of the enzyme.
Seventy-one pyrimidine analogs have been tested as possible inhibitors of human spleen mitochondrial dihydroorotate dehydrogenase. Of these nine were demonstrated to be effective inhibitors of the enzymic activity. Two compounds, dihydro-5-azaorotate and 6-thiobarbiturate appeared to be specific inhibitors of the DHO-DHase. In addition, three compounds, 5-azaorotate, 5-bromoorotate, and barbiturate were also inhibitory against the two subsequent enzymes of the pathway, orotate phosphoribosyltransferase and orotidylate decarboxylase, so that they could act against three enzymes of the mammalian pyrimidine de novo biosynthetic pathway.
D001463:Barbiturates / Q000494:pharmacology; D004081:Dihydroorotate Oxidase / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009962:Orotate Phosphoribosyltransferase / Q000037:antagonists & inhibitors; D009963:Orotic Acid / Q000494:pharmacology; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000037:antagonists & inhibitors; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013154:Spleen / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013858:Thiobarbiturates / Q000494:pharmacology
D001463:Barbiturates; D011743:Pyrimidines; D013858:Thiobarbiturates; D009963:Orotic Acid; D010088:Oxidoreductases; D004081:Dihydroorotate Oxidase; D009962:Orotate Phosphoribosyltransferase; D009964:Orotidine-5'-Phosphate Decarboxylase; C029684:thiobarbituric acid; C032232:barbituric acid