Hemoglobin I & II

Question 1

Basic equipment of Hemoglobin’s binding site

Answer 1

beta-2 F8 contains proximal histidine
beta 2-E7 contains distal histidine
alpha1 C chain interfaces “elbow point” on alpha chain, causes conformational alteration in the other subunits to be optimally primed for oxygen uptake

process of oxygen uptake initially occurs in beta2, F helice

heme group containing iron

Question 2

Bonding patterns in hemoglobin

Answer 2

beta 2 F8’s proximal histidine chelates Fe2+’s 5th coordination site, pulling it .4 angstroms from the plane

oxygen binds to Fe2+’s sixth coordination site

Oxygen forms superoxide stabilized by distil histidine donating a hydrogen bond to prevent free radical

Fe in 3+ state is called methahemoglobin, usless molecule

Question 3

when when you find heme’s iron group in a +3 valence state, and what do we call this group?

Answer 3

oxidizing agents (toxins )

methemoglobin

Question 4

Iron in heme and free iron

Answer 4

Iron is stabilized in the 2+ state in heme, and momentarily oxidized to 3+ during the binding of oxygen which pulls it BACK INTO THE PLANE of the porpheryn ring

Question 5

3 blood plasma proteins, site functions and why

Answer 5

haptoglobin: grabs hemoglobin
hemopexin: grabs free heme in blood
transferin: grabs free iron

iron is toxic, catalytically producing free radicals in the blood.

Question 6

hemoglobins fetal to adult

Answer 6

fetuses have alpha gamma (ay) hemoglobin subunits

by one year gamma has been “shut down” and betas have been activated.

Question 7

Typically oxygen binds to ____ first

Answer 7

beta, F8 proximal histidine

Question 8

Sicle Cell: why

Answer 8

amino acid substitution between a hydrophobic valine (interior) and a hydrophilic amino acid (glutamine)

Question 9

Sicle cell: where

Answer 9

beta chain

Question 10

Beta chain diseases are typically

Answer 10

worse than alpha chain diseases

Question 11

Hb S

Answer 11

sicle cell anemia, Hb A wildtype

Question 12

How does methemoglobin relinquish its oxygen?

Answer 12

methemoglobin reductase, which is an NADH: it contributes electrons to the iron and reduces it

the distal histidine also assists

Question 13

Allosteric activity of hemoglobin

Answer 13

conformation change due to stimulation at a site other than oxygen binding site

can inhibit or stimulate oxygen

Question 14

Hemoglobins conformation states

Answer 14

R state (oxygenated) and T (deoxygenated)

Question 15

Homologous Proteins to Hemoglobin

Answer 15

myoglobin: takes oxygen FROM rbcs, does not supply them.

has a higher affinity for oxygen than RBCs

Question 16

Allosterics: H and CO2

Answer 16

protons bind to hemoglobin —> T conformational state (BOHR EFFECT) Low pH

CO2 bind to hemoglobin —> T state

Question 17

pH of a muscle cell is

Answer 17

between 7.2-7.4, very acidic environment

Question 18

Haldane Effect

Answer 18

Oxygen drives off the CO2 and H in the lungs

Question 19

Glycolysis does what

Answer 19

produces H in the cells

Question 20

2,3-BPG

Answer 20

will be elevated in response to living in a higher altitude

negative allosteric effector: enhances offloading of oxygen

Question 21

H–Hb–CO2 is the result of the

Answer 21

bohr effect (rightward shift)

result of mass action

more O2 in tissues, more CO2 in RBCs

Question 22

O2-Hb is the result of the

Answer 22

Haldane effect, O2 diffuses into lungs and replaces CO2 and protons

Question 23

Evolutionary Time Line of Hemoglobin: from Leg-to Hemo

Answer 23

DIVERGED 800+ million years ago leghemoglobin/myoglobin/hemoglobin alpha/hemoglobin delta

DIVERGED 500+ million years ago
myoglobin, alpha and beta hemoglobins

DIVERGED 350+ million years ago
Hemoglobin alpha from hemoglobin beta

Question 24

Hemoglobin A has

Answer 24

alpha2beta2 adults

Question 25

Hemoglobin A2

Answer 25

alpha2delta2 adults, 2%

Question 26

Hemoglobin F

Answer 26

gamma chains (fetal)

Question 27

What is the mutation in the hemoglobin F that allows it to have a higher affinity for oxygen than hemoglobin A?

Answer 27

residue that binds 2,3 diphosphglycerate

Question 28

Heme

Answer 28

heterocyclic tetrapyrole structure (porphyrin ring) with an iron molecule in the middle planar AND hydrophobic bound to globin chain

Question 29

What kind of cooperativity does myoglobin have?

Answer 29

the OPPOSITE of cooperativity: it's just ONE subunit, a different gene, and holds on to oxygen

Question 30

What molecules are in the RBC?

Answer 30

1) hemoglobin 2) molecules involved in pyruvate 3) methemoglobin reductase 4) enzyme responsible for converting intermediate in glycolysis from 1,3-DPG to 2,3-DPG

Question 31

Which way will the oxygen curve shift in the presence of 2,3-DPG

Answer 31

rightward, reduced affinity for oxygen

Question 32

RBCs need atp? if so, why?

Answer 32

work, keeping out sodium and calcium