Bilirubin oxidation in brain

Bilirubin is a product of heme catabolism which by virtue of its lipid solu bility can cross the blood-brain barrier and enter the brain. Neonatal jaun dice is a common transitional phenomenon which is due to the combination of increased heme catabolism and rate limitations as far as hepatic conjugati on and biliary excretion of bilirubin, In the great majority of cases this is an innocuous condition, which is even posited to have some beneficial ef fects due to the ability of bilirubin to quench free oxygen radicals. Howev er, because bilirubin is neurotoxic, hyperbilirubinemia in the newborn may exceptionally result in death in the neonatal period, or survival with seve re neurological sequelae (kernicterus). Bilirubin enters the brain through an intact blood-brain barrier, Clearance of bilirubin from brain partly inv olves retro-transfer through the blood-brain barrier, and possibly also thr ough the brain-CSF barrier into CSF. Work in our lab during the past 5 year s has substantiated earlier work which had suggested that bilirubin may als o be metabolized in brain, The responsible enzyme is found on the inner mit ochondrial membrane, and oxidizes bilirubin at a rate of 100-300 pmol bilir u-bin/mg protein/minute. The enzyme activity is lower in the newborn compar ed with the mature animal, and is also lower in neurons compared with glia. Studies of different rat strains have documented genetic variability. The enzyme is cytochrome-c-dependent, but has as yet not been unequivocally ide ntified. The rate of oxidation of bilirubin is such that this enzyme probab ly contributes meaningfully to the clearance of bilirubin from brain. (C) 2 000 Academic Press.