Regulation of rat liver tryptophan pyrrolase by its cofactor haem: Experiments with haematin and 5-aminolaevulinate and comparison with the substrate and hormonal mechanisms.
1. The administration of haematin or 5-aminolaevulinate to rat enhances the activity of liver tryptophan pyrrolase; both endogenous and newly formed apoenzymes become strongly haem-saturated. Haem activation does not stabilize tryptophan pyrrolase. 2. Actinomycin D, puromycin or cycloheximide prevent the activation of the enzyme by 5-aminolaevulinate but not that by haematin. The latter is inhibited by haem-destroying porphyrogens. 3. The combined injection of either haematin or 5-aminolaevulinate with cortisol does not produce an additive effect, whereas potentation is observed when tryptophan is jointly given with either the cofactor or the haem precursor. 4. Further experiments on the substrate (tryptophan) mechanism of pyrrolase regulation are reported, and a comparison between this and the cofactor and hormonal mechanisms is made. 5. It is suggested that the substrate mechanism may also involve increased haem synthesis. 6. The role of tryptophan pyrrolase in the utilization of liver haem, and as a possible model for the exacerbation by drugs of human hepatic porphyrias, is discussed.
D000622:Aminolevulinic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001051:Apoenzymes / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006397:Hematinics / Q000494:pharmacology; D006418:Heme / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D006854:Hydrocortisone / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D011164:Porphyrias / Q000378:metabolism; D011165:Porphyrinogens / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D001051:Apoenzymes; D006397:Hematinics; D011165:Porphyrinogens; D003609:Dactinomycin; D006418:Heme; D011691:Puromycin; D000622:Aminolevulinic Acid; D014364:Tryptophan; D003513:Cycloheximide; D014366:Tryptophan Oxygenase; D006854:Hydrocortisone