Globular Proteins: Hemoglobin and Myoglobin

Question 1

structure and function of myoglobin

Answer 1

in muscles, accepts oxygen from hemoglobin and releases to cytochrome oxidase (complex VI)

prosthetic group - heme

8 helical segments, hydrophobic pockets binds one heme.

proximal histidine - coordinates iron in the heme

distal histidine - binds O2 on iron

Question 2

cooperative binding

Answer 2

the binding between O2 and Hemoglobin is cooperative.

can be positive or negative

negative cooperativity - when binding decreasing the affinity for further ligand binding

measured by hill’s coefficient
greater than 1 is Pos, less than 1 is neg

Question 3

noncooperative binding

Answer 3

binding between Myoglobin and O2 in non-cooperative

Question 4

allostery

Answer 4

where biological macromolecules binds to a secondary spot on the protein and changes the binding ability of the functional site

allosteric effectors - O2, 2,3-BPG, CO2, pH (Bohr effect)

Question 5

Bohr effect

Answer 5

oxygen binding causes release of H+. Low pH favors stabilizes T form, decreases oxygen affinity of hemoglobin. Working muscle has a lower pH

Question 6

pulse oximeters

Answer 6

a method of measuring percentage of hemoglobin carrying Oxygen.

Question 7

oxygen binding to hemoglobin

Answer 7

positive cooperativity in that after the fist O binds weakly the affinity increases

hill’s coefficient is 3

Question 8

oxygen binding to hemoglobin

Answer 8

binding of oxygen triggers R form - movement of iron into the plane of heme (through proximal histidine)

positive cooperativity in that after the fist O binds weakly the affinity increases

hill’s coefficient is 3

R-T conformational change model: R (relaxed) has high oxygen affinity. T (tense) has low oxygen affinity

Question 9

2,3-BPG

Answer 9

binds btwn two beta subunits. Has higher affinity for the T form and stabilizes t form

BPG is required to lower hemoglobins oxy affinity so that the oxy will move to myoglobin in the working muscles

BPG concentration increases in higher altitudes, CO2 stabilizes deoxy form (T)

Question 10

2,3-BPG

Answer 10

binds btwn two beta subunits. Has higher affinity for the T form and stabilizes t form

BPG is required to lower hemoglobins oxy affinity so that the oxy will move to myoglobin in the working muscles

BPG concentration increases in higher altitudes, CO2 stabilizes deoxy form (T)

increase Temp stabilizes T form

Question 11

carbon monoxide poisoning

Answer 11

CO binds with a 240 fold greater oxygen affinity than oxygen. Binding increases hemoglobin affinity for oxygen to the point that there is decreased oxygen unloading into the tissue

reversibile by hyperbaric oxygen

symptoms - headache, confusion, myocardial ischemia, malaise, syncope, ventricular arrhythmias, dizziness, coma, pulmonary edema, nausea, seizure and profound lactic acidosis

Question 12

Hemoglobinopathies

Answer 12

group of genetic disorders causes by abnormal hemoglobin molecule

by mutation or insufficient quantities

examples: sickle cell anemia, hemoglobin C disease, Hb Hammersmith, Hb Savannah, Hb Milwaukee, Methemoglobinemias and Thalassemias

Question 13

Sickle Cell Anemia

Answer 13

a hemoglobinopathy

point mutation in beta chain gene (Glutamate is replaced by Valine)

Causes a hydrophobic patch, forms aggregates with other deoxy Hbs

red cell breakdown, anemia, capillary occlusion and pain in extremities (like in high oxygen demanding activities like exercise)

treatment: hydroxyurea - induces excess synthesis of fetal hemoglobin

Question 14

Hemoglobin C disease

Answer 14

mutation in 6th position of beta chain, causes mild anemia.

substituting K for E

Question 15

Hb Hammersmith

Answer 15

F42S which breaks hydrophobic barrier around the heme and allowing water access to the pocket. Results in heme loss

Question 16

Hb Savannah

Answer 16

G24V of beta chain, increases steric hinderance between two helices increase instability of hemoglobin

Question 17

Hb Milwaukee

Answer 17

H87E of beta chain, stabalizes the dysfunctional methemaglobin (iron is ferric Fe3+ form)

methemaglobin can also be caused by NADH-methemoglobin reductase deficiency
-treatment of methylene blue

Question 18

Thalassemias

Answer 18

imbalance of globin chains

alpha-Thalassemias: less functional hemoglobin causing silent to mild to severe anemia

beta-Thalassemias: reduction in the synthesis of beta chain

Question 19

glycosylated hemoglobin

Answer 19

HbA1c

seen in diabetes mellitus, blood sugar levels may be consistently high

HbA is glycosylated which produces Hb A1c

this is a clinical indicator of uncontrolled high blood sugar for the past couple of months