Hemoglobin and Myoglobin

Myoglobin is most abundant in

Skeletal and cardiac muscle

Hemoglobin is most abundant in

Red blood cells

Myoglobin primary function

Oxygen storage

Hemoglobin primary function

Oxygen transport and CO₂ transport

Protein with highest oxygen affinity

Myoglobin

Protein optimized for oxygen delivery

Hemoglobin

Heme contains

Ferrous iron (Fe²⁺)

Iron state that binds oxygen

Fe²⁺

Iron state that cannot bind oxygen

Fe³⁺

Methemoglobin

Hemoglobin containing Fe³⁺

Globin fold

Eight α-helices (A–H) forming a heme pocket

Proximal histidine (F8)

Anchors Fe²⁺ to the globin protein

Distal histidine (E7)

Stabilizes bound O₂ and prevents iron oxidation

Myoglobin structure

Monomer with one heme group

Hemoglobin structure

Tetramer (α₂β₂) with four heme groups

Structural feature enabling cooperativity

Hemoglobin quaternary structure

Myoglobin oxygen-binding curve

Hyperbolic

Hemoglobin oxygen-binding curve

Sigmoidal

Cause of sigmoidal curve

Cooperative oxygen binding

T state

Low-oxygen-affinity conformation

R state

High-oxygen-affinity conformation

Primary determinant of oxygen binding

Partial pressure of oxygen (pO₂)

P₅₀

pO₂ at which hemoglobin is 50% saturated

Increased P₅₀

Decreased oxygen affinity

Negative allosteric effectors of hemoglobin

H⁺, CO₂, 2,3-BPG

Effect of negative allosteric effectors

Stabilize T state and promote oxygen release

Bohr effect

Decreased oxygen affinity due to increased H⁺ and CO₂

Hydrogen ions (H⁺) effect

Promote salt bridge formation and stabilize T state

Carbon dioxide direct binding

Forms carbaminohemoglobin

Carbaminohemoglobin

Hemoglobin with CO₂ bound to N-terminal amino groups

2,3-BPG binding site

Central cavity between β-chains

Hemoglobin state that binds 2,3-BPG

Deoxygenated (T state)

Conditions increasing 2,3-BPG

High altitude, chronic hypoxia, chronic anemia

Positive allosteric effector of hemoglobin

Carbon monoxide (CO)

CO affinity relative to oxygen

~220 times greater

Effect of CO on hemoglobin

Locks hemoglobin in R state and prevents oxygen release

Carboxyhemoglobin

Hemoglobin bound to carbon monoxide

Fetal hemoglobin (HbF)

α₂γ₂

Adult hemoglobin (HbA)

α₂β₂

Minor adult hemoglobin (HbA₂)

α₂δ₂

Reason HbF has higher oxygen affinity

Weak binding to 2,3-BPG

Sickle cell disease mutation

Glu → Val substitution at β6

HbS polymerizes when

Deoxygenated

Triggers of sickling

Low oxygen, dehydration, acidosis, fever, high altitude

Primary cause of sickle cell anemia

HbS polymerization and RBC fragility

Thalassemia

Reduced or absent globin chain synthesis

α-thalassemia

Decreased α-globin production

β-thalassemia

Decreased β-globin production

β-thalassemia major

Severe anemia due to lack of β-chain synthesis