Hemoglobin Flashcards
What is another term for erythrocyte?
Red blood cell
What is erythropoeisis?
From pluripotent stem cells erythrocites are produced. This starts in the bone marrow
What are pluripotent stem cells?
Cells that are completely undifferentiated and depend on extracellular signals to dictate what it is going to become
What is the process of erythropoeisis?
A single cell is going to divide and then a signal is given and then it divides again. From one cell 2^11 mature erythrocytes are formed
What happens to the intracellular material in a erythrocyte?
It is ejected out and is becomes just a bag of hemoglobin
What is necessary for the production of many erythrocytes?
A lot of DNA is needed, folic acid and iron
What is needed with folic acid and why?
B12 because folic acid can mask the symptoms of deficiency of B12
True or false?
Erythocytes are created in waves every 120 days
False. A steady stream of new blood is needed. Constantly producing and constantly deleting blood cells
Why do cancer drugs contain anti folates?
Messes with the folic acid system and cant make DNA and therefore kill the cancer
Why do cancer chemotherapy patients experience anemia?
Because they cant make the DNA necessary for this erythropoeisis
When blood is centrifuged what do the layers contain?
Cellular material goes to the bottom and non cellular goes to the top
What is the cellular material in blood called?
Hermatocrite and is about 50% of the blood. Packed with blood
What is the difference between plasma and serum?
Plasma: Has an anti coagulate added to the blood and becomes the layer at top when centrifuged
Serum: Blood coagulates first then spun; becomes the top as well
Once the noncellular portion is removed from blood and spun in centrifuge what is the top layer called?
Buffy coat - represents the leukocytes. Very thin layer
How do red blood cells get their shape?
A specialized cytoskeleton system that laminates the innermembrane. Attaches to the inner membrane and actively deform through microcirculation (test tube capillaries)
What is lost during the aging of blood cells?
The ability to deform. They are then recognized and deleted
What is in blood cells?
Hemoglobin at 37% solution. ATP Source, Pentophosphate pathway, other upport pathways but no organelles.
Why are there no mitochondria in blood cells?
Because it would steal the O2 and it would be a conflict of interest
What is anemia and what are indications of anemia
Low red blood cell count is anemia. Indications are low hermatocrite and hemoglobin. Other tests include paleness of blood which indicates low iron
What type of Quaternary structure does hemoglobin have and how many chains?
Tetramer and four globin chains. Tetrameric structure is important
How many different types of subunits does hemoglobin have?
Two. Alpha and beta
For every terameric structure how many heme groups and irons are in hemoglobin?
Four heme groups and four irons
Why is iron toxic?
If in the blood it will catalytically produce free radicals. Iron can go back and forth between 2+ and 3+. Can spontaneously react with proteins and DNA
What is a free radical?
An electron that is unpaired
What is “crashing” of a red blood cell and what can cause it?
Crash is the release of intracellular materials from red blood cells and can be caused in severe situations especially rigorous exercise like marathons
What are the 3 plasma proteins that grab released intracellular material of a crashed red blood cell?
Heptaglobin - grabs hemoglobin
Hemopexin - grabs heme
Transferin - Grabs iron
How many helices are in a subunit of a hemoglobin?
8 alpha helicies
Which two His participate in the control of oxygen bonding to the iron and the heme?
E7 and F8
Where is Heme located in a subunit of hemoglobin?
Between the E,F and G helices in a hydrophobic pocket
What are two characteristics of Heme?
Flat and fat (hydrophobic)
What is the name for the His located at E7?
Distal His
What is the name for the His located at F8?
Proximal His
Is F8 or E7 closer to the iron and chelates?
F8
What is a chelate?
a compound containing a ligand (typically organic) bonded to a central metal atom at two or more points
What is iron held by?
An organic compound
What is the 5th chelation point?
Proximal F8 His
What does the 5th F8 chelation do to iron
Pulls the iron out of the plane. There are four other chelation points around the hem and form a plane and iron is stuck symmetrically in the plane.
What is the 6th Chelation
Oxygen
What does the 6th chelation do?
Oxygen the 6th chelation, will come in on the other side and bind to iron and click it into place.
When the 6th chelation is added what happens to the molecule as a whole?
Iron clicking into place initiates a cascade that the whole molecule clicks into a different shape
What are the types of globin chains?
Alpha-like and beta-like chains
What are the sub-types of globin chains?
Alpha-like: zeta and alpha
Beta-like: epsilon, gamma, delta, beta
What is a leghemoglobin?
Plant protein - active area of research
A fertilized egg has what types of globin chains?
Zeta and epsilon
At the stage of a fetal what types of globin chains are in hemoglobin?
Alpha and gamma
By the age of one year what types of globin chains are in hemoglobin?
Alpha and beta
What is the normal globin chains found in adults? What is the new combinations recently developed (20 million years)
Alpha2 and beta2 are normal
Alpha2 and Delta2 are evolutionarily new
What chain does oxygen bind to first?
Beta chain
What are the two dimers of a hemoglobin?
Alpha 1 beta 1
Alpha 2 beta 2
Sickle cells look sickle because of what issue?
14 hemoglobin molecules bundle up and want to rip out. Growing pole vault polymerizing and starts to bend against the sides of the cell.
Why do red blood cells need to be deformable?
In order to pass through the micro capillary bed and wiggle through. The blood vessels have a narrower diameter than red blood cells.
What happens when a sickle cells passes through narrow blood capillary beds
Cell is too large and it rips
How many mutations cause sickle cell?
1
Where is the mutation that causes sickle cell?
On the a helix on the with amino acid (A6). The beta chain. Normally it is a glutamate but it goes to a valine in sickle cell. Nonconservative substitution.
Why can’t the A6 amino acid be a valine instead of glutamate?
Glutamate is acidic and hydrophillic and valine is branched and hydrophobic. Nonconservative. There is a hydrophobic patch on the outside. And that patch becomes more extreme in the deoxygenated state.
What is the function of hemoglobin?
Transport oxygen
What are the mechanism of O2 binding to hemoglobin?
Fe 2+ : O2 binding sites
Cooperativity
Reversible binding
Also steric control
What will help athletes in performance?
Veomax. Maximum volume of oxygen one can consume. How much oxygen you can get to muscles
What is blood doping
Add red blood cells in blood to increase compacity of vO2
Oxygen binds to what molecule in hemoglobin and it what oxidative state?
Iron Fe 2+.
What is meth hemoglobin
When Fe is in 3+ state. Oxidized state. Can bind to hemoglobin but can’t be relinquish
When meth hemoglobin forms what enzyme fixes it?
Meth hemoglobin reductase which requires Cytochrome B5 and NADH to supply the electrons.
What is cooperativity?
Biochemistry concept in which subunits interact with on another
What is allosteric control
Compounds that do not bind to the active sites. Bind elsewhere to change the conformations. H+ and CO2 force hemoglobin to the T state.
What is the R state and T state of hemoglobin?
R-oxygenated
T-deoxygenated
Myoglobin does what to oxygen?
Remove it from hemoglobin
What is the structure of myoglobin?
Monomer that has one globin chain and one heme iron
What has a higher affinity for oxygen. Myoglobin or hemoglobin
Myoglobin
True or False:
The genes that form the alpha and beta subunits of hemoglobin are homologous?
True
