Patterns of porphyrin accumulation in response to chemicals in chick embryo liver cells.
Four patterns of porphyrin accumulation were observed by high-pressure liquid chromatography when chemicals were added to chick embryo liver cells. These patterns provide a guide to the site of action of the chemicals. Protoporphyrin accumulated in response to 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC), a result consistent with its ability to inhibit ferrochelatase. Uroporphyrin and heptacarboxylic acid porphyrin accumulated in response to 3,3',4,4'-tetrachlorobiphenyl, 2,2',4,4',6,6'-hexachlorobiphenyl, and 3,5-diethoxycarbonyl-2,4,6-trimethylpyridine, a result suggesting inhibition of uroporphyrinogen decarboxylase. Coproporphyrin was the major porphyrin to accumulate in response to allylisopropylacetamide, aromatic amides, and steroids, a result suggesting inhibition of coproporphyrinogen oxidase. A mixture of uroporphyrin, heptacarboxylic acid porphyrin and coproporphyrin accumulated in response to aromatic di- and mono-esters, aliphatic diesters, and aliphatic amides. The pattern observed after addition of excess delta-aminolevulinic acid (ALA) the endogenous substrate of the pathway to the cells was proto- greater than copro- greater than uro-porphyrin. This pattern resembled that produced by DDC but by none of the other chemicals. It was concluded that porphyrin accumulation can not be attributed solely to the induction of ALA-synthetase. It appears that porphyrin-inducing chemicals exert an additional effect on one or other of the enzymes of the heme biosynthetic pathway.
D000622:Aminolevulinic Acid / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002851:Chromatography, High Pressure Liquid; D003997:Dicarbethoxydihydrocollidine / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism*
D011166:Porphyrins; D003997:Dicarbethoxydihydrocollidine; D000622:Aminolevulinic Acid