Screening for the ability of hexachlorobenzene metabolites to decrease rat liver porphyrinogen carboxy-lyase.
In order to examine inhibitory effects of hexachlorobenzene metabolites on the hepatic porphyrinogen carboxylyase activity, rat liver cytosol was incubated with uroporphyrinogen III and chlorinated phenols, thiophenols, thioanisoles and benzenes. Then, the occurrence of hepta-, hexa-, penta- and tetracarboxyporphyrinogen = coproporphyrinogen (measured as porphyrins) was determined. Inhibitory effects were exerted by tetrachlorohydroquinone, pentachlorophenol, pentachlorothiophenol, 1,2,3,5- and 1,2,4,5-tetrachlorobenzene. Other compounds including hexachlorobenzene which was tested for comparative reasons did not impair uroporphyrinogen decarboxylation. In the presence of tetrachlorohydroquinone, uroporphyrinogen merely was decarboxylated to hepta- and hexacarboxyporphyrinogen. Under the influence of the other 4 compounds with inhibitory effects, pentacarboxyporphyrinogen and coproporphyrinogen were formed additionally. Coproporphyrinogen formation was inhibited completely by tetrachlorohydroquinone, while pentachlorophenol diminished its formation by about 50% and pentachlorothiophenol, 1,2,3,5- and 1,2,4,5-tetrachlorobenzene by less than 10%.
S C
SC
Billi
G
G
Koss
L C
LC
San Martin de Viale
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D002722:Chlorobenzenes / Q000494:pharmacology; D002733:Chlorophenols / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D005260:Female; D006581:Hexachlorobenzene / Q000031:analogs & derivatives* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D051381:Rats; D014577:Uroporphyrinogens / Q000378:metabolism
D002722:Chlorobenzenes; D002733:Chlorophenols; D014577:Uroporphyrinogens; D006581:Hexachlorobenzene; C003060:pentachlorobenzene; D002262:Carboxy-Lyases; C022430:porphyrinogen carboxy-lyase