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212_spring_2005_heme synthesis

212_spring_2005_heme synthesis - BethA.Bouchard BIOC212:...

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Pathophysiology of Heme Synthesis Beth A. Bouchard BIOC 212:  Biochemistry of Human Disease Spring 2005
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HEME-CONTAINING PROTEINS  Hemoglobin  Myoglobin  Cytochromes  Catalase  Some peroxidases
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Iron Utilization
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STRUCTURE OF HEME Ferrous iron (Fe 2+ ) Protoporphyrin IX:  contains  4 pyrrole rings linked together  by methenyl bridges
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Heme 8 8 Succinyl CoA Glycine** HEME SYNTHESIS ** Amino acid (building blocks of protein) synthesized in your body
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Heme  synthesis
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HEME SYNTHESIS
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HEME SYNTHESIS:  Red blood cells 85% of total heme synthesis occurs in red  blood cells (RBC) Ceases when RBC’s mature Heme stimulates protein synthesis in  reticulocytes Synthesis is regulated at the level of the  enzymes ferrochelatase* and porphobilinogen  deaminase**
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** *
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HEME SYNTHESIS:  Liver The liver is the main non-RBC source of heme synthesis Heme produced in the liver is used mainly for the synthesis of the  cytochrome P 450  class of enzymes that are involved in detoxification Regulated at level of ALA synthase: Formation of 5-ALA is the rate- limiting step in heme synthesis in the liver
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Formation of 5-aminolevulinate (5-ALA) 5-ALA  5-ALA is formed in the mitochondria and transported  to the cytoplasm
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