any molecule which is reversibly bound by a protein
What is induced fit?
when the binding of a ligand causes a conformational change in a protein that alters its function.
What is a binding site?
a site on the protein which is complimentary in size, shape, charge, and/or hydrophobicity to a specific ligand where it binds
What is the binding site of an enzyme called?
an active site
What is Myoglobin (Mb)
a monomeric protein that facilitates oxygen transport in peripheral tissue
What is Hemoglobin (Hb)?
tetrameric protein found in erythrocytes (red blood cells) that transports oxygen from lungs to the periphery.
What is the structure of Myoglobin?
Myoglobin is a small globular protein which consists of: i) a single polypeptide chain of 153 residues arranged in eight α-helices.
ii) heme (iron porphyrin) prosthetic group (covalently-bound, non-polypeptide component required for function)
What is P50?
the amount (partial pressure) of oxygen required to half-saturate myoglobin
What is the formula for the affinity for oxygen?
What are the 3 challenges of Oxygen transport?
-Solubility of oxygen in serum is too low for passive diffusion.
-None of the amino acid side chains is suited for reversible oxygen binding.
-Transition state metals have strong tendency to bind oxygen (but also a strong tendency to produce damaging free radicals).
What is a Heme complex?
A ring system that utilizes the oxygen binding properties of Fe while preventing free radical formation by filling its other bonds, to achieve oxygen storage and delivery
What are Allosteric effectors (modulators)?
molecules that regulate a proteins actions by binding to a protein at a site separate from the functional binding site (may be activators or inhibitors).
What is a homotropic interaction?
When the normal ligand and modulator are the same
What is a heterotropic interaction?
when the modulator is different from the normal ligand
What are allosteric proteins?
proteins regulated by allosteric effectors
What doallosteric activators do?
stabilize the R state (relaxed) of a protein
What do allosteric inhibitors do?
stabilize the T state (tense) of a protein
What is the oxygen saturation of Myoglobin at 30tor(the start of pheripheral tissue)?
What is the oxygen saturation of Myoglobin at 100tor(lungs)?
Theshape of the Hemoglobin binding curve shows positive cooperativity. What does this mean?
O2 affinity increases as O2 is bound
in T state Where is iron wiht regards to the heme ring?
iron is outsidethe heme ring
What happens structurally as the iron of a sub unit binds to the first oxygen of a hemoglobin molecule?
-binding O2 moves iron into plane of the ring (R state)
-this movement causes structural changes which are translated to other subunits putting them in R state
what is 2,3 Biphospho-D-glycerate?
-2,3 BPG is an allosteric heterotropic modulator of hemoglobin.
-Lowers affinity for oxygen, stabilizes t-state
How does 2,3 BPG bind to Hemoglobin?
2,3 BPG carries five units of negative charge and binds to positively charged pocket of deoxyhemoglobin.
How many residues bind 2,3,BPH in adults Hemoglobin vs fetus'?
-Adult Hb has six (+) residues for 2,3BPG binding,
-fetal Hb has only five.
When does the body increase 2,3 BPG production?
High altitudes where less oxygen is taken in by the lungs
What are the two ways CO2 is removefrom the body by red blood cells?
1)2 is taken up into red blood cells and converted to bicarbonate and a proton by the enzyme carbonic anhydrase.
2) CO2 binds as a carbamate group to the N terminus of eachchain of hemoglobin to form a carbamino-terminal residue.
What is the effect of CO2 uptake on red blood cells and hemoglobin?
-Ph is lowered by release of protons which causes hemoglobins affinity for oxygen to decrease resulting in oxygen release
What happens to Hemoglobins affinity for oxygen times in situations where pH drops (such as during physical exercise)?
Affinity decreases and more oxygen is released
What happens at the primary structure of hemoglobin in sickle cell anemia?
a single aminoacid change (Glu6Val)
In what state of Hemoglobin does sickle cell anemia reveal itself and How?
in its De-oxygenated state the valine which is not hydrophilic is pulled in to the hydrophobic center of the molecule causeing a stiff sickle shape so these molecules fit together easily to form fibers
How does sickle cell anemia help deter malaria?
-when the blood cell is attacked it lowers its pH
-This deoxygenates Hemoglobin putting it in its sickle shape