-4x pyrrole rings, held together by methine bridges, decorated with 2x propionate, 4 methyl, and 2 vinyl groups

-Fe²⁺ in center (Held by N's of Pyrrole Rings)

-Heme group is O2 binding site

Hemoglobin

-HbA: tetramer of 2 α-globin and 2 β-globin (4 heme groups)

HbF: Tetramer of 2 α-globin and 2 γ-globin

-α-Helical 2ry structure

-Compact, spherical 3ry structure

-Gap in center

Myoglobin

-Monomer (one heme group)

-Strictly α-helical

-Tightly packed to protect heme

-No nucleus

-No mitochondria

-Do not consume any of the O2 transported

Hemoglobin

-Sigmoidal indicates cooperative binding (binding of 1 O2 subunit increases affinity of other 3)

Myoglobin

-Hyperbolic indicates non-cooperative binding

Tense form in absense of O2

Relaxed form when fully oxygenated

2,3 BPG

Binds to center cavity of deoxyglobin (T State) and decreases O2 affinity

Note: Hemoglobin is a vibrating molecule, so even when O2 is bound, it will eventually hit the right size for 2,3 BPG to bind. This forces the molecule into the T State and O2 is released

HbF has 2 γ subunits (as opposed to 2 β in HbA)

γ has much lower affinity for 2,3 BPG thus a higher affinity for O2

-Elevated H+ levels lower pH and Decrease O2 affinity

-Protons are involved in intersubunit salt bonds in T state; the salt bridges stabilize 4ry structure of deoxyhemoglobin

Homotropic Allosteric Modulators

What are they? What do they do? Give an example

-Substrate for the target enzyme

-Typically an activator

-Ex) O2 & Hemoglobin; O2 binding promotes further O2 binding (positive cooperativity)

Heterotropic Allosteric Modulators

What are they? What do they do? Give an example

-Not a substrate for the target enzyme

-May be either activator or inhibitor

Ex) H+ and Deoxyhemoglobin; Stabilizes 4ry structure and promotes release of O2 

-CO2 produced in tissues diffuses into RBC

-Majority converted to bicarbonate by carbonic anhydrase and leaves cell in exchange for Cl^- ion (chloride shift)

-Process reverses in lungs, diffuses to tissue, and expired

-Binds water, reducing the pKa from 15.7 to 7.  

-This polarizes the water and causes it to lose a proton. 

-Strong nucleophilic attack on CO2 to make hydration occur and form bicarbonate 

-Without zinc, rxn would never be fast enough

Mechanism of Carbonic Anhydrase

(this is just a picture to help you visualize)

-Competes with O2 for binding to Heme Group Fe²⁺

-Much stronger affinity than O2, loss of sigmoidal curve indicates loss of cooperative binding

-Treat with hyperbaric O2 that will eventually outcompete CO

-Contains oxidized ferric iron (Fe³⁺); useless as O2 transporter

-Causes left shift

-Treat with methylene blue; reduces back to ferrous iron

Sickle Cell

How does it occur? Complications? Why is it prevalent in malaria countries?

-HbS results from mutation replacing Glu with Val

-Val faces hydrophobic patch of adjacent tetramer causing them to associate and form long, stiff fibers

-Very poor O2 transport; plugs venules

Polymerization effects ability of parasite to digest Hb; increases chance of host survival