Hemoglobin Structure and Function

heme is made of—

• protoporphyrin IX (C, H, N)

• central ferrous iron atom (Fe_²⁺)

• 4 heme groups → 4 O₂

globin is made of—

4 tetramer globin chains with

• 2 identical pairs of unlike peptide chains

• Ex: 2 alpha 2 beta

transferrin

transports iron in ferric state

ferritin

stores iron

hemosiderin

intracellular iron storage (macrophages consuming RBC)

protoporphyrin synthesis occurs in—

mitochondria and cytoplasm of precursor RBC in BM

protoporphyrin synthesis

glycine + succinyl CoA

→ delta ALA

→ porphobilinogen (PBG)

→ uroporphyrinogen (UPG)

→ coproporphyrinogen (CPG)

→ protoporphyrinogen IX

→ protoporphyrin IX (PP)

→ PP IX + Fe²⁺
→ HEME

globins have usually —

2 alpha chains and 2 non-alpha chains

embryonic hemoglobins

Gower 1

Gower 2

Portland

Gower 1

2 zeta 2 epsilon

Gower 2

2 alpha 2 epsilon

Portland

2 zeta 2 gamma

Hgb F

2 alpha 2 gamma

• fetal hemoglobin

• <2% in adults

Hgb A

2 alpha 2 beta

• 95-97% in adults

Hgb A2

2 alpha 2 delta

• 2-3% in adults

sideroblast

nucleated RBC with iron excess

siderocyte

mature RBC with iron excess

prussian blue

iron stain

2,3 BPG helps to—

offload oxygen from RBCs

deoxyhemoglobin and 2,3 BPG

2,3 BPG squeezes between 2 beta chains causing a salt bridge that expels oxygen

oxyhemoglobin and 2,3 BPG

oxygen is picked up and 2,3 BPG is squeezed out

more 2,3 BPG means oxygen affinity—

decreases

less 2,3 BPG means oxygen affinity—

increases

right shift oxygen affinity curve

• increase temperature

• increase [H+]

• increase 2,3 BPG

left shift oxygen affinity curve

• decrease temperature

• decrease [H+]

• decrease 2,3 BPG

carboxyhemoglobin

carbon monoxide (CO) on hemoglobin

• reversible with a lot of oxygen to outcompete CO

• normal CO = 0.2-0.8%

methemoglobin

ferric state of hemoglobin

• reversible with ascorbic acid (vit C) or methylene blue

sulfhemoglobin

sulfur atom instead of ferrous iron in heme

• irreversible, wait for turnover (120 days)

aging RBC

• increase calcium

• decrease ATP

• decrease sialic acid (sticky)

• Na/K pumps fail = water in cell

heme in RBC is broken down—

and stored in transferrin as iron

globin in RBCs is broken down and recycled to—

amino acid pool

protoporphyrin in RBC is—

excreted as urobilinogen

extravascular hemolysis

reticuloendothelial system (spleen + BM)

• majority of RBC breakdown

intravascular hemolysis

free Hgb in blood enters liver

• haptoglobin