生物化学教学课件：Chapter11 Metabolism of Non-nutritional Substances.pptVIP

Liver Cholesterol Bile salts Dietary Fat Emulsifies dietary fat Fat gets absorbed 95% Enterohepatic  circulation 5% (in the stools) Affect of Dietary Fiber Drugs: ion exchange resins  (cholestyramine) Blood Cholesterol Stored in the gallbladder Increases ? Overview of bile salt metabolism Section Ⅲ. Biosynthesis of heme M=methyl P=propionate V=vinyl Substituents: A B C D Heme Methenyl bridge 1. Biosynthesis of heme (in liver, bone marrow) Gly, succinyl-CoA, Fe2+ Materials: Site: in mitochondria and cytosol Processes: 1) ALA synthesis 2) PBG synthesis 3) UPG and CPG synthesis 4) Heme synthesis （ALA） ALA synthase (Coenzyme: Pyridoxal phosphate) The processes of heme synthesis (key enzyme) in mitochondria Heme feedback inhibition Θ ALA dehydrase (ALA enters the cytosol) (PBG) 胆色素原 3NH2 NH2 4CO2 deaminase Linear tetrapyrrole cosynthase decarboxylase Uroporphyrinogen III Coproporphyrinogen III Fe2+ ferrochalatase globin Hb Coproporphyrinogen III (into Mit) 6H 2CO2 decarboxylase oxidase Protoporphyrin IX Heme Protoporphyrinogen Into cytosol 原卟啉原IX 原卟啉原IX Materials: succinyl-CoA, glycine and Fe2+. The initial reaction and the last three occur in mitochondria; The intermediate steps occur in the cytosol. Synthesized mainly in liver and bone marrow but mature red blood cells lack mitochondria and are unable to synthesize heme. key enzyme: ALA synthase (coenzyme: pyridoxal phosphate. Summary 2. Regulation of heme synthesis 1) ALA synthase (The major regulatory step) (-) Gly + succinyl-CoA ALA heme (-) (+) VitB6 , MHb sterol hormone feedback inhibition 2) ALA dehydrase and ferrochelatase They are sensitive to heavy metal, such as plumbum. So plumbum toxicosis