Rat-liver porphyrinogen carboxy-lyase inhibition as a function of the degree of hexachlorobenzene-induced porphyria

Abstract

This study aimed to confirm the presence of an inhibitor in the hexachlorobenzene-porphyric liver that is able to decrease the normal activity of porphyrinogen carboxy-lyase (PCL), to determine whether any relation exists between the degree of hexachlorobenzene-induced porphyria and the ability of a porphyric liver preparation to reduce the enzyme activity of normal liver and to seek extraction methods in order to characterize the inhibitor by gas-liquid chromatography. A perfused liver supernatant (11,000 X g) filtered through a Sephadex G-25 column and heated for 5 min at 100 degrees C was used as the inhibitor source. The results show that the inhibitor was eluted together with a protein peak by gel filtration, the inhibitor was thermostable, the extent of the inhibitory effect reached by this preparation increased with the degree of porphyria, ether and toluene extracts from both heated and non-heated porphyric liver preparations also exhibited an inhibitory effect on the normal activity of PCL and the degree of inhibition depended on the amount of the preparation added. Therefore, there is an inhibitor of PCL activity in the hexachlorobenzene-porphyric liver, the concentration of which increases as the degree of porphyria increases. This inhibitor is soluble in organic solvents and is presently being characterized by gas-liquid chromatography.