卡马西平对血红素生物合成途径的影响。
The influence of carbamazepine on the heme biosynthetic pathway.
作者信息
Schoenfeld N, Greenblat Y, Epstein O, Atsmon A
出版信息
Biochem Med. 1985 Dec;34(3):280-6. doi: 10.1016/0006-2944(85)90089-4.
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.
卡马西平是一种广泛用于治疗神经系统疾病的药物，在培养的鸡胚肝细胞中具有致卟啉效应。它使细胞卟啉浓度增加了80倍，δ-氨基-γ-酮戊酸合酶活性增加了4倍。卟啉积累的增加先于δ-氨基-γ-酮戊酸合酶活性的增加。对δ-氨基-γ-酮戊酸脱水酶、胆色素原脱氨酶和尿卟啉原脱羧酶活性的测量表明，卡马西平对尿卟啉原脱羧酶的抑制作用高达近50%，对胆色素原脱氨酶活性的抑制作用高达20%，但不影响δ-氨基-γ-酮戊酸脱水酶的活性。卟啉的积累模式，主要是尿卟啉和七羧基卟啉，与尿卟啉原脱羧酶的抑制作用相符。因此，我们可以得出结论，卡马西平在鸡胚肝细胞单层中的致卟啉效应是其对尿卟啉原脱羧酶活性的抑制作用的结果。
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