L4-Hb Structure,synthesis And Breakdown Flashcards
What is hemoglobin and what is its importance
Globular proteins found excessively in RBCs
it’s responsible for O2 transport from the lungs to the tissues for use in metabolism
also it transports protons and carbon dioxide from tissues to lungs
Where is hemoglobin synthesized
In progenitors of red blood cells and cannot occur in mature RBC’s
Heme and globin are made separately within the cell before their assembly in cytosol
How is the final heterotetramer of an HB molecule produced
When the globin chains are released from the ribosomes and heme molecules diffuse from the mitochondria the globin chains fold around the heme molecules to produce it
What are the polypeptide subunits in Hb
Two alpha and to beta subunits held together by noncovalent interactions
Each globin chain is Bound together to a heme moiety
What is heme
Porphyrin ring bound to reduced ferrous iron at its center by four covalent bonds
How many O2s does the iron bind to
Each heme binds to 1 O2 reversibly for a total of 4 O2 molecules
Where does heme sit and how does this structure help
Sits within the globin chain hydrophobic pocket which is lined by nonpolar amino acids with the exception to two histidine residues
this helps stabilizing the binding of O2 to heme Fe2+ by preventing its oxidation to Fe3+ when oxygen binds
What are the states in which hemoglobin exists
Low affinity taut/closed state=deoxyhb
high affinity relaxed/open state=oxyhb
How does hemoglobin exhibit positive cooperativity
The binding of 1 O2 molecules to One heme group in deoxyhemoglobin increases affinity for O2 in adjacent heme units allowing hemoglobin to deliver more O2 to the tissues in response to relatively small changes in the PO2
What is the characteristic shape of the oxygen hemoglobin dissociation curve
Sigmoidal shape
A characteristic of positive cooperativity (allosteric effect)
What are the Allosteric effectors that influence equilibrium between the t and R forms
CO2
H+
the special product of glycolysis in erythrocytes 2,3 bisphosphoglycerate is synthesized from 1,3 BPG an intermediate of glycolysis in RBC’s
What is the functions of heme synthesis
Hemoglobin
cytochromes
myoglobin
What is the location of synthesis of heme
Involves both the mitochondria and the cytosol
Occurs in nearly every cell
For Hb synthesis it occurs in RBC progenitor cells
What are the steps of heme synthesis
Synthesized by precursors glycine and succinyl coenzyme A by a series of reactions:
▪️ glycine and succinyl-CoA condense to form Delta Aminolevulinic acid(ALA) using b6 as a co factor for delta ALA synthase
▪️ Two molecules of Delta ALA condense to form the pyrrole porphobilinogen mediated by ALA dehydratase
▪️4 porphobilinogen condenses to make a series of porphyrins:
By enzymes:
Porphobilinogen deaminase
Uroporphorinogen decarboxylase
▪️ poryhrins are altered by decarboxylation oxidation and protoporphyrin IX is formed
▪️ Photoporphrin IX binds iron Fe +2 forming heme
How does regulation of heme synthesis occur
ALA synthase is rate limiting enzyme it requires B6 and is inhibited by heme
When the amount of heme available exceeds the amount of the core proteins ALA synthase in the liver is inhibited by heme to reduce flux through the pathway
1-in this case of Fe2+ iron in the heme is oxidized to the ferric Fe3+ state forming hemin
2-Hemin inhibits ALA synthase Both by feedback using an allosteric mechanism and also by regulating ALA synthase gene expression by repressing it’s transcription
