BMB401 ANGELA Review-1

BMB401 ANGELA Review-1 - LECTURE 11 Heme Synthesis...

Info iconThis preview shows pages 1–3. Sign up to view the full content.

View Full Document Right Arrow Icon
LECTURE 11 Heme Synthesis Formation of protoporhyrin IX o Asymmetric ring structure o Requres chelation of iron Requires o 4 mitochondrial enzymes o 4 cytosolic enzymes Reaction1: Condensation between succinyl CoA and Glycine occurring in mitochondrial matrix Enzyme: α- Aminolevulinate Synthase (ALA) Happens in the mitochondrial matrix Atleast one of the reactants is activated (liberation of CoA and CO 2 helps drive it forward o Regulation primarily by negative feedback (most highly regulated step) Transport of α -ALA into the mitochondrion is blocked by high heme concentration. ALA synthase is synthesized in cytosol, block the entry from cytosol to matrix you can block the action Transcription of D-ALA synthase Messenter stability Translation: Negative feedback by heme reduces translation of α -ALA mRNA **it degrades quickly so it goes away quickly Reaction 2: Dehydration Synthesis Transport to cytosol 2 molecules of α- ALA condenses to form each porphobilinogen molecule **It takes 8 molecules of for 4 porphobilinogen Reaction 3: Condensation Link 4 molecules of porphobilinogen head to tail to form a linear tetrapyrrole molecule o Releases 1 ammonium ion for each methylene bridge made Enzyme: Porphobilinogen Deaminase
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Reaction 4: Cyclization Synthesis of an asymmetric ring (Uroporphyrinogen III) Enzyme: Uroporphyrinogen III synthase o Also called Uroporphyrinogen III cosynthase because it requires a cosynthase to form the asymmetric ring o Cosynthase flips one pyrool (APAPA PPA ) o Formation of uroporphynogen 1 leads to build up of byproducts in tissues Next Few Reactions Form methyl and vinyl side chains, and alter saturation of ring constituents, finally ending with protporphyrin IX. o Takes place in mitochondrion on the innermembrane Finally ferrous Iron, Fe 2+ is chelated o Enzyme: Ferrochelatase o (PP IX is transported to matrix where iron is chlated) 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 o In a molecule called ferritin that acts as intracellular iron storage o 24 subunits organisms make into ball like structure with (hollow core) o In the hollow core is where iron is localized o Localization of iron in ferritin protein allows it to be kept in a soluble easily accessed form Comes from diet on the protein Transferrin o Can only carry 2 o Binds to transferring 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:
Background image of page 2
Image of page 3
This is the end of the preview. Sign up to access the rest of the document.

Page1 / 32

BMB401 ANGELA Review-1 - LECTURE 11 Heme Synthesis...

This preview shows document pages 1 - 3. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online