N-alkylation of exogenous haem analogues caused by drugs in isolated hepatocytes. Structural isomerism and chirality of the resulting porphyrins.
Isolated rat hepatocytes incubated with two suicide substrates of cytochrome P-450, 2-allyl-2-isopropylacetamide and 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine(4-ethyl-DD C), convert exogenous mesohaem and deuterohaem into N-alkylated mesoporphyrins and deuteroporphyrins respectively. The N-alkylated mesoporphyrins can be separated by h.p.l.c. from the corresponding N-alkylated protoporphyrins originating from endogenous haem; in this way the contribution of both endogenous and exogenous pools of haem can be studied in the same experiment. N-Alkylated mesoporphyrin exhibits chiral properties, and its isomeric composition and/or amount are dependent on the particular cytochrome P-450 enzyme predominating in the cell. These findings provide additional and more direct evidence that exchangeable haem is taken up by cytochrome P-450 before being N-alkylated.
D000081:Acetamides / Q000494:pharmacology*; D000502:Allylisopropylacetamide / Q000494:pharmacology*; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003905:Deuteroporphyrins / Q000378:metabolism; D003997:Dicarbethoxydihydrocollidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008652:Mesoporphyrins / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011166:Porphyrins / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D019324:beta-Naphthoflavone
D000081:Acetamides; D001571:Benzoflavones; D003905:Deuteroporphyrins; D008652:Mesoporphyrins; D011166:Porphyrins; D011725:Pyridines; C030826:3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine; C029198:deuteroheme; D000502:Allylisopropylacetamide; C031468:mesoporphyrin IX; D019324:beta-Naphthoflavone; D003997:Dicarbethoxydihydrocollidine; D010634:Phenobarbital