Brenner D A, Bloomer J R
N Engl J Med. 1980 Apr 3;302(14):765-9. doi: 10.1056/NEJM198004033021401.
Fecal protoporphyrin is increased in patients with variegate porphyria, even during clinical remission, suggesting an enzymatic defect in the terminal portion of the heme biosynthetic pathway. We measured the activities of protoporphyrinogen oxidase, which catalyzes the oxidation of protoporphyrinogen to protoporphyrin, and heme synthase, which catalyzes the chelation of iron to protoporphyrins, in cultured skin fibroblasts from five normal controls and five patients with variegate porphyria. Heme synthase activity was shown to be normal in variegate porphyria cells by direct assay in cell sonicates and indirect assay in intact cells. Protoporphyrinogen oxidase activity, however, was reduced to 43 per cent of normal in sonicates of variegate porphyria cells (0.90 +/- 0.13 vs. 2.12 +/- 0.25 nmol of protoporphyrin per milligram of protein per hour [mean +/- S.E.M.] [P less than 0.005]). We conclude that protoporphyrinogen oxidase activity is deficient in variegate porphyria. Fecal protoporphyrin may increase because an excess amount of protoporphyrinogen is excreted into bile and subsequently auto-oxidized to protoporphyrin.
在杂合性卟啉病患者中，即使在临床缓解期，粪便原卟啉也会增加，这表明血红素生物合成途径末端存在酶缺陷。我们测定了来自5名正常对照者和5名杂合性卟啉病患者的培养皮肤成纤维细胞中原卟啉原氧化酶（催化原卟啉原氧化为原卟啉）和血红素合酶（催化铁与原卟啉螯合）的活性。通过对细胞超声裂解物的直接测定和对完整细胞的间接测定表明，杂合性卟啉病细胞中的血红素合酶活性正常。然而，杂合性卟啉病细胞超声裂解物中的原卟啉原氧化酶活性降至正常的43%（每毫克蛋白每小时0.90±0.13 vs. 2.12±0.25 nmol原卟啉[平均值±标准误][P<0.005]）。我们得出结论，杂合性卟啉病中原卟啉原氧化酶活性缺乏。粪便原卟啉可能增加是因为过量的原卟啉原排泄到胆汁中，随后自动氧化为原卟啉。
