Figure: hemecatabolism
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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
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
- 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