BMB401-EXAM 2 SG - LECTURE 11 Heme Synthesis Reaction 1:...

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LECTURE 11 Heme Synthesis Reaction 1: succinyl CoA + Glycine (mt matrix) ALA o Regulation : negative feedback (most highly regulated step) Transport of α -ALA synthase into the mitochondrion is blocked by high heme concentration. (ALA synthase is made in cytosol, block the entry from cytosol to matrix blocks action) Transcription of D-ALA synthase Messenger stability Translation: Negative feedback by heme reduces translation of α -ALA mRNA **it degrades quickly so it goes away quickly Reaction 2: ( ALA to cytosol) 8 ALA 4 Porphobilinogen Reaction 3: 4 Porphobilinogen Linear tetrapyrole Link 4 molecules of porphobilinogen head to tail to form a linear tetrapyrrole molecule o Releases 3 ammonium ion for 3 methylene bridge made Enzyme: Porphobilinogen Deaminase Reaction 4: Cyclization: Synthesis of asymmetric ring ( Uroporphyrinogen III) Enzyme: Uroporphyrinogen III synthase (aka Uro III cosynthase) o Cosynthase forms asymmetric ring- flips 1 pyrolle (APAPA PPA ) o Formation of uroporphynogen 1 leads to build up of byproducts in tissues Next Few Reactions Form methyl & vinyl side chains, & alter saturation of ring constituents, finally ending with protoporphyrin IX. o In inner mb mitochondrion Finally ferrous Iron, Fe 2+ is chelated Enzyme: Ferrochelatase o (PP IX is transported to matrix where iron is chelated) Where does iron come from? Free iron is toxic because it can donate and accept electrons and acts as catalyst in O 2 Iron must be sequestered (in ferritin ) o Ferritin - intracellular iron storage, iron sequestered in ferritin o 24 subunits organisms make into ball like structure with (hollow core- where iron localized) o Localization of iron in ferritin – keeps in soluble easily accessed form Comes from diet on the protein Transferrin o Can only carry 2 Fe3+ o Binds to transferrin receptor (endocytosed into the cell in endosytic vesicle and through the pathway. Vessel is acidified and iron is dropped.) o Transferrin is recycled by transporting it through the exocytic pathway through the cell. Porphyrias:
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o Acute intermittent porphyria Reaction 3 – Porphobilinogen Deaminase Deficiency Porphobilinogen and α- ALA excess SXS include: Severe abdominal pain/ Neurologic involvement because it looks like Gabba o Congenital erythropoietic pophyria o o normal (asymmetric) Abnormal- each A separated by a P; symmetric absorbs light Reaction 4 – Cosynthase deficiency Uro I- symmetric ring- made in addition to Uroporphyrinogen III. Urophoyrinogen I has no use, this ring and its metabolites build up, because they can’t be used. SXS include: Photosensitivity/
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This note was uploaded on 10/18/2011 for the course BMB 401 taught by Professor Kaguni during the Fall '08 term at Michigan State University.

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BMB401-EXAM 2 SG - LECTURE 11 Heme Synthesis Reaction 1:...

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