Tryptophan pyrrolase in haem regulation. The relationship between the depletion of rat liver tryptophan pyrrolase haem and the enhancement of 5-aminolaevulinate synthase activity by 2-allyl-2-isopropylacetamide.
Rat liver tryptophan pyrrolase haem is maximally depleted at 30 min after administration of a 400 mg/kg dose of 2-allyl-2-isopropylacetamide. This depletion lasts for 24 h, by which time 5-aminoleevulinate synthase activity becomes maximally enhanced. 2. though the above maximum depletion of pyrrolase haem (at 0.5h) is also produced by a 100 mg/kg dose of the porphyrogen, this does not enhance synthase activity at 24 h.  It and smaller doses, however, cause a smaller but earlier enhancement of synthase activity (maximum at 2 h) and produce a similarly short-lived deplation of pyrrolase haem. 3. The depletion of pyrrolase haem and the enhancement of synthase activity by the porphyrogen are inhibited by compound SKF 525-A and phenazine methosulphate, and are potentiated by nicotinamide but not by phenobarbitone. Phenazine methosulphate and nicotinamide also exert opposite effects on hexobarbital sleeping-time. 4. 2-Allyl-2-isopropylacetamde also the depletes pyrrolase haem in vitro. It does so in liver homogenates of control rats in the presence, and in those of phenobarbitone-treated rats in the absence of added NADPH. 5. A discussion of the present results in relation to previous work with other haemoproteins suggests that, whereas cytochrome P-450 (haem) is primarily involved in the production of the active (porphyrogenic) metabolite(s) of 2-allyl-2-isopropylacetamide, the haem pool used by tryptophan pyrrolase may play an important role in the effects of this compound on haem biosynthesis.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism*; D000081:Acetamides / Q000494:pharmacology*; D000502:Allylisopropylacetamide / Q000494:pharmacology*; D000818:Animals; D006418:Heme / Q000378:metabolism*; D006591:Hexobarbital / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology; D051381:Rats; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D000081:Acetamides; D009536:Niacinamide; D008773:Methylphenazonium Methosulfate; D000502:Allylisopropylacetamide; D006418:Heme; D006591:Hexobarbital; D014366:Tryptophan Oxygenase; D000624:5-Aminolevulinate Synthetase