The influence of carbamazepine on the heme biosynthetic pathway.
Carbamazepine, a drug which is widely used in neurological diseases, has a porphyrogenic effect in chick embryo liver cells in culture. It increased the concentration of cellular porphyrins by 80-fold and delta-aminolevulinate synthase activity by 4-fold. The increase in the accumulation of porphyrins preceded that of ALAS activity. Measurements of the activities of aminolevulinate dehydrase, porphobilinogen deaminase, and uroporphyrinogen decarboxylase showed that C inhibits UROD up to nearly 50% and PBGD activity up to 20%, but does not affect the activity of ALAD. The pattern of accumulation of porphyrins, mainly uro- and heptacarboxylporphyrin, is compatible with an inhibition of UROD. We may, therefore, conclude that the porphyrogenic effect of C in monolayers of chick embryo liver cells is the result of its inhibitory effect on the activity of UROD.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000502:Allylisopropylacetamide / Q000494:pharmacology; D000818:Animals; D002220:Carbamazepine / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004357:Drug Synergism; D006418:Heme / Q000096:biosynthesis*; D011163:Hydroxymethylbilane Synthase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D000623:Porphobilinogen Synthase / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D013997:Time Factors; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism
D011166:Porphyrins; D011506:Proteins; D000502:Allylisopropylacetamide; D002220:Carbamazepine; D006418:Heme; D000624:5-Aminolevulinate Synthetase; D011163:Hydroxymethylbilane Synthase; D014575:Uroporphyrinogen Decarboxylase; D000623:Porphobilinogen Synthase