title: Porphyrin metabolism and haem biosynthesis in Gilbert's syndrome.
abstract: 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.
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000097:blood; D000328:Adult; D001663:Bilirubin / Q000097:blood; D005260:Female; D005420:Flavoproteins; D005878:Gilbert Disease / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D006418:Heme / Q000096:biosynthesis*; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D010088:Oxidoreductases / Q000097:blood; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011164:Porphyrias / Q000097:blood / Q000201:enzymology; D011166:Porphyrins / Q000378:metabolism*; D050768:Protoporphyrinogen Oxidase; D012293:Rifampin / Q000627:therapeutic use
chemical_list: D005420:Flavoproteins; D024101:Mitochondrial Proteins; D011166:Porphyrins; D006418:Heme; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493978:PPOX protein, human; D050768:Protoporphyrinogen Oxidase; D000624:5-Aminolevulinate Synthetase; D001663:Bilirubin; D012293:Rifampin