BCHM 561 Exam 2 chapter 7

2,3 BPG

2,3 BPG in red blood cells is crucial in determining the oxygen affinity of hemoglobin stabilizes and binds in the T state, facilitates release of oxygen from metabolism binds to His and Lys

distal histidine

A histidine located near the heme group in myoglobin and hemoglobin that helps maintain the heme iron in the Fe2+, stabilizing and preventing release. Hemoglobin with Fe3+ is called methemoglobin and it doesnt bind O2

What is the primary source of H+ that leads to the displacement of O2 from Hemoglobin in tissues?

Carbonic acid an increase in pCO2 results in the production of H+ through a reaction catalyzed by carbonic anhydrase

Iron that binds O2

Ferrous iron (Fe2+) binds O2 Ferric iron (Fe3+) does not when oxygen binds, it straightens the Fe bonds.

sickle cell anemia

HbS has a Glu to Val mutation in Beta chain creating a hydrophobic patch if just one beta chain has Val, its a carrier, if both have it, its fatal clots blood flow through capillaries decreasing O2 delivery

sodium nitrite and methemoglobin

NaNO2 converts Fe2+ to Fe3+ it is used in food preservatives and stuff pulse oximeters cant detect differences in methemoglobin vs hemoglobin

Why would a patient with 20% carboxyhemoglobin have significant symptoms from a blood donation?

That means that there is CO, which inhibits the release of oxygen.

How can you reduce sickle cell symptoms?

by adding a precursor to gamma chains, that form HbF because HbF patients have reduced symptoms

Carbon monoxide

carbon monoxide disrupts oxygen transport by hemoglobin by binding 200 times more tightly than oxygen it shifts the curve to the left, forcing the R state, which prevents delivery to tissues.

hemoglobin models of cooperativity

concerted model - binding one O2 shifts all subunits to the R state with high affinity sequential model - binding O2 only shifts that subunit to the R state with high affinity hemoglobin really has both features, closer to sequential early on, and concerted later (more O2 means more affinity bleed to subunits)

Cooperativity and oxygen delivery in hemoglobin

cooperativity enhances oxygen delivery by hemoglobin

pH and oxygen affinity

decreased pH (more H+) results in decreasing the O2 affinity by stabilzing T state increased CO2 also decreases O2 affinity by stabilizing T state, the CO2 forms carbamate Bohr effect

fetal hemoglobin (HbF)

has a lower affinity for 2,3 BPG, because it has a Ser instead of a His this means it has a higher affinity for O2, helping to bring O2 to the fetus

role of hemoglobin and its function

hemoglobin delivers oxygen to tissues it needs to bind and release O2

human hemoglobin

hemoglobin in humans is an assembly of four myoglobin like subunits two identical alpha chains and two identical beta chains

what type of bond is responsible for the aggregation of deoxy HbS resulting from the Glu to Val transition

hydrophobic bond Glu to Val substitutes a hydrophobic Val for a hydrophlic Glu

what is one approach to treat sickle cell anemia?

increased potassium will cause increased volume of red blood cells due to osmotic effect, which in turns lowers the concentration of deoxy-HbS

Beta thalassemia major

leads to aggregation of unstable alpha or beta globin chains

HbM (Methemoglobin)

mutations in the alpha or beta chain, oxidation to Fe3+.

myoglobin vs hemoglobin

myoglobin -1 polypeptide chain -no quaternary structure -high O2 affinity -in muscles hemoglobin -4 polypeptide chains -heterotetramer -variable O2 affinity -in red blood cells

heme iron

prosthetic group (tightly bound molecule essential for function)

Beta and alpha Thalassemia

thalassemias hereditary hemolytic diseases due to imbalance of globin chains beta or alpha(HbH) thalassemia is from reduced or absent beta/alpha synthesis cause by mutations that reduce mRNA

hemoglobin states

the quaternary structure of deoxyhemoglobin is the T state the quaternary structure of oxyhemoglobin is the R state the T state is rotated 15' compared to the R state (stabilized by ionic bonds)

The structure of myoglobins effect on reactive oxygen

the structure of myoglobin prevents the release of reactive oxygen species the bond between iron and oxygen exists as resonance structures, which stabilizes the bond (prevents O2-)