McColl K E, Thompson G G, el Omar E, Moore M R, Goldberg A
Gut. 1987 Feb;28(2):125-30. doi: 10.1136/gut.28.2.125.
Studies in 14 patients with unconjugated hyperbilirubinaemia caused by Gilbert's syndrome have revealed abnormalities of the enzymes of haem biosynthesis measured in peripheral blood cells. The activity of the penultimate enzyme of haem biosynthesis protoporphyrinogen (PROTO) oxidase was reduced at 3.1 +/- 2.6 nmol PROTO/g protein/h (mean +/- ISD) compared with 8.2 +/- 5.1 in controls (p less than 0.005). This was associated with a compensatory increase in the activity of the initial and rate controlling enzyme of the pathway delta-aminolaevulinic acid (ALA) synthase at 866 +/- 636 nmol ALA/g/protein/h compared with 156 +/- 63 in controls (p less than 0.001). Unlike variegate porphyria in which there is a genetic deficiency of PROTO oxidase there was no increased excretion of porphyrins or their precursors in Gilbert's syndrome. Accentuation and subsequent correction of the unconjugated hyperbilirubinaemia with rifampicin produced reciprocal changes in PROTO oxidase activity indicating that bilirubin may be inhibiting the activity of this enzyme.
对14例因吉尔伯特综合征导致非结合胆红素血症患者的研究显示,在外周血细胞中测得的血红素生物合成酶存在异常。与对照组的8.2±5.1相比,血红素生物合成倒数第二个酶原卟啉原(PROTO)氧化酶的活性降低至3.1±2.6 nmol PROTO/g蛋白/h(平均值±标准差)(p<0.005)。这与该途径初始和速率控制酶δ-氨基乙酰丙酸(ALA)合酶活性的代偿性增加有关,与对照组的156±63相比,其活性为866±636 nmol ALA/g蛋白/h(p<0.001)。与存在PROTO氧化酶遗传缺陷的杂合性卟啉症不同,吉尔伯特综合征中卟啉或其前体的排泄没有增加。用利福平加重并随后纠正非结合胆红素血症后,PROTO氧化酶活性发生相反变化,表明胆红素可能抑制该酶的活性。