heme catabolism

Biochemistry: - the 1st step in the degradation of heme is the formation of biliverdin catalyzed by heme oxygenase within macrophages - the reaction produces carbon monoxide - biliverdin is in turn converted to bilirubin in a reaction catalyzed by biliverdin reductase - bilirubin complexes with albumin in plasma as it leaves the macrophage - hepatocytes in the liver take up bilirubin & conjugate it to glucuronic acid for elimination into the bile ' see figure === catabolic pathway === - heme catabolism 1 - substrate: hemoglobin (within erythrocyte) - product: heme (within smooth endoplasmic reticulum of macrophage in spleen) - heme catabolism 2 - enzyme: ((multienzymecomplex (hemeoxygenase-1/Cyt P450 reductase) - substrate: heme + O₂ + NADPH - product: biliverdin + CO + NADP - occurs within smooth endoplasmic reticulum of macrophage in spleen - heme catabolism 3 - enzyme: biliverdin reductase - substrate: biliverdin + NADPH - product: bilirubin + NADP - occurs within smooth endoplasmic reticulum of macrophage in spleen - heme catabolism 4 - translocation of bilirubin from smooth endoplasmic reticulum of macrophage in spleen to plasma - heme catabolism 5 - substrate: bilirubin + albumin - product: bilirubin-albumin complex in plasma - heme catabolism 6 - substrate: bilirubin-albumin complex in plasma - product: bilirubin within smooth endoplasmic reticulum of hepatocyte - heme catabolism 7 - enzyme: UDP-glucuronosyltransferase-1A - substrate: bilirubin + 2 UDP-glucuronate - product: bilirubin-diglucuronide + 2 UDP - reaction occurs in the smooth endoplasmic reticulum & releases bilirubin-diglucuronide into cytoplasm of hepatocyte

References

Biochemistry, L. Stryer, WH Freeman & Co, New York, 1988 pg 596-597