Hemoglobin and Myoglobin

Question 1

myoglobin

Answer 1

single polypeptide chain
globular, w/ covalently attached heme group (porphyrin containing Fe)
O2 storage in muscles
has a higher affinity for O2 than hemoglobin

Question 2

hemoglobin

Answer 2

tetramer w/ 2 beta and 2 alpha sununits
each subunit has a heme group (porphyrin containing Fe)
ability to bind 4 O2
cooperative binding and allosteric effects ([H+], 2,3 BPG)

Question 3

prothetic group

Answer 3

heme prothetic groups are needed in myoglobin and hemoglobin because O2 doesn’t bind well to AAs
pophyrin: composed of pyrrole rings linked by methane bridges
is flat with two open sites for binding O2 at the Fe2+
will only bind O2 when in ferrous (reduced) state/Fe2+
will not bind O2 in the ferric (oxidized) state/Fe3+

Question 4

methemoglobin

Answer 4

hemoglobin who’s heme has been oxidized to Fe3+

won’t bind O2

Question 5

NADH-methemoglobin reductase

Answer 5

(met-Hgb red)

reduces Fe3+ (ferric) to Fe2+ (ferrous)

Question 6

how does the structure of myoglobin, or hemoglobin subunits, affect O2 binding?

Answer 6

O2 binds w/in a cavity created by val E11 and phe CD1
the PROXIMAL histidine , His F8, blocks O2 from binding at the bottom of the heme
the DISTAL histidine, His E7, is more flexible and will allow O2 to bind in the hydrophobic cavity created by val and phe
when O2 binds, distal his is moved from its original position (angled away from F3, to being in line, or in front of, Fe -> conformational change -> pulling heme closer to porphyrin ring -> distorting shape of alpha helix
the hydrophobicity of val and phe near the binding site of O2 don’t make the bond unstable but they do make it easier to remove when needed in the tissues

Question 7

T and R state

Answer 7

T=tense
R=relaxed -> has much higher affinity for binding O2

w/o O2 T state is more stable because it has a lot of ion pairs

allosteric effect

at any time you can find an ave of 3 O2 bound to hemoglobin

Question 8

Allosteric Effects of O2 binding hemoglobin

Answer 8

inc [H+] / dec pH –> Hb release O2 (Bohr effect)
dec [H+] / inc Ph –> Hb inc affinity for O2

inc [CO2] (hypoventilation) -> dec pH/inc [H+]
dec [CO2] (hyperventilation) -> inc pH/dec [H+]
CO2 + H2O H+ + HCO3-

inc [2,3BPG] –> Hb release O2
because 2,3BPG binds pos charged groups and stabalizes deoxyHb, making it easier, and more favorable, to release O2

Question 9

CO poisoning

Answer 9

CO has a higher affinity for Hemoglobin than O2 does

Question 10

NO and hemogobin

Answer 10

NO can bind to a hemoglobin subunit in place of one of the O2
then is transferred to cys of beta subunit
upon offloading hemoglobin passes NO to GSH and it binds to receptors in vascular smooth muscle cells relaxing them, and facilitating passage of O2 into the tissue
helps tissues receive O2 at high altitudes

Question 11

adult vs infant hemoglobin

Answer 11

adult normal hemoglobin = 2 alpha and 2 beta
infant normal hemoglobin = 2 alpha and 2 gamma

after birth, gamma should dec as the beta inc

bad if this doesn’t happen because infant hemoglobin has a higher affinity to O2 than adult hemoglobin

Question 12

Sickle cell anemia

Answer 12

Glu6 -> val6

beta subunits on hemoglobin are defective and take on sickle shape when exposed to low [O2], or deoxyHb factors (low pH, 2,3BPG, high CO2)
misshapen RBC can block blood vessels and prove fatal

sickleing doesn’t occur in oxyHb because the phe85 and val88 that val6 normally hydrophobically react with in deoxyHb conditions to cause issues, are buried in the oxyHb conformation

Question 13

hemoglobin C

Answer 13

glu6 -> lys6 in beta gene

mild hemolytic anemia

Question 14

hemoglobin SC

Answer 14

one beta-globin gene has glu6 -> val6 defect and the other beta-globin gene has glu6 -> lys6 defect

these people are normal until giving birth of surgery

Question 15

thalassemias

Answer 15

can result from mutation in either alpha-globin or beta-globin gene

alpha thalassemia: caused by mutation in one or more of the 4 alpha-globin gene copies. If 3 genes defective->hemoglobin binds O2 too tightly. If 4 genes defective-> fetal fatalis

beta thalassemia: each chromosome should have two copies of the beta-globin gene, and each only has one. causes alpha-globin aggregates to precipitate; vary in severity, minor cases usually don’t need treatment, major cases can be severely anemic, require blood transfusions, iron overload, bone marrow replacement, or death

Question 16

globular proteins

Answer 16

soluble in H2O w/ hydrophobic ends toward the core
they are the most numerous of the cellular proteins
stabilized by H bonds, ionic interactions, and disulfide bonds
the large # of H bonds neutralizes the polarity of the -NH and C=O bonds