Hemaglobin

Question 1

Gas transport and pH regulation

What is Hb

How does O2 and CO2 get in and out of the body

Answer 1

Hb is a protein designed to take O2 from the lungs to tissues and to take help CO2 be taken back to the lungs

O2 has really low solubility in the plasma, so O2 that reaches the tissues is carried in RBCs bound to Hb

RBCs contain carbonic anhydrase that converts CO2–> H2CO3–> HCO3+ and H+ which is soluble in plasma and RBC cytosol (with a little CO2 in Hb)

Question 2

Tertiary Structure of myglobin and Hb

Answer 2

Hb. is a tetra protein of 2 alpha and 2 beta that are similar to myglobin (in muscles)

Both contain Heme group (Fe2+ ferrous form of iron that actually)

Question 3

Structure-function relationship in myoglobin and Hb

Answer 3

Myoglobin gives a normal hyperbolic binding curve

Hb gives sigmoidal cooperative binding of O2

Question 4

Fetal Hb (HbF)

Answer 4

HbF (2-alpha, 2-gamma) has a higher affinity for O2 than HbA so that it can draw O2 from mom in placenta

Question 5

Sequential cooperatively of Hb bound to O2

Answer 5

binding of one subunit of O2 will higher the affinity for the rest R state (high affinity), T state (low affinity)

Question 6

Carbon monoxide poisining

Answer 6

CO has a really high affinity to Hb and Will lock in R state

Question 7

How does O2 change conformation of Hb subunit

Answer 7

deoxy Hb has a His that pulls Fe2 from the porphyrin ring, when O 2 is present it pulls Fe2 in the plane of ring and shifts the whole Hb molecule to favor the R group more favorably

Question 8

Allosteric regulators and effecots

Answer 8

allosteric regulator is a molecule that binds to a protein that alters the affinity for a substrate at some other site

Regulators: H+, Co2, and 2,3 DPG all bind to Hb and reduce affinity for O2 and O2 does the reverse

H+ and CO2 are negative heterotropic allosteric effectors
O2 is a positive homotropic allosteric effector

“called the bohr effect or isohydric shift”

H+ binding changes bc of shifts in pKa due to microenvironment changes

Question 9

2,3 DPG

Answer 9

negative heterotropic allosteric effectors of O2 binding

binds to a specific site in a central cavity between B subunits

It lowers affinity for O2 thats needed when O2 levels are low (high altitudes) so that O2 levels dissociate easier to give O 2 to tissues (stabilizes T state)

Without it DPG Hb is more like myoglobin

Question 10

How temp affects Hb

Answer 10

at higher Temp ie fever, you lower o2 affinity bc you need to get O 2 more to tissues

Question 11

Sickle Cell anemia

Answer 11

Homozygous recessive disease
point mutation of Val for Glu in B adult gene –> HbS

Val creates sticky patch on deoxy Hb–> polymerization iinto long chains, creating fibers that sickle the shape cant get through the microcirculation and causes hemolytic anemia

Question 12

Rate of polymerization of Hb depends on what variables

Answer 12

1. degree of deoxygenation: pH, ionic strength, temp, deoxy forms the polymers
2. intracellular HbS concentration
3. amount of HbF present

Dysregulation of cell volume causes leaky ions and dehydration of cell causing concentration to go up

surface area exposure of adhesion molecules

Question 13

therapy to SCA

Answer 13

hydroxy urea: stimulates HbF production

L-glutamine

Question 14

Thalassemias

Answer 14

an imbalance in concentration of Beta and alpha subunits

alpha thalassemia: too little alpha globin genes (rarly syptomatic)
beta thalassemia: too little beta you get

Question 15

HbC and HbA1C

Answer 15

B- point mutation Lys for Glu mild hemolytic anemia, HBSC

HbA1C- glycosylated Hb high in diabetics