Porphyrins Structure

Here are the study notes:

Porphyrins

• Porphyrins are cyclic compounds formed by the linkage of four pyrrole rings through methenyl bridges (-HC=)
• Porphyrin rings are numbered with Roman numerals I through IV, starting at the top and proceeding clockwise
• Methenyl bridges are lettered with Greek letters, alpha through delta, again proceeding clockwise
• Common substituents are often abbreviated, e.g. A = acetic acid, P = propionic acid, M = methyl, V = vinyl

Hemoproteins

• Hemoproteins are proteins that contain heme (iron-protoporphyrin)
• Examples of hemoproteins in humans and animals:
  • Hemoglobin (Hb) in red blood cells (RBCs)
  • Myoglobin (Mb) in muscle tissue
  • Cytochrome c in electron transport chain
  • Cytochrome P450 in xenobiotic metabolism
  • Catalase in hydrogen peroxide degradation
  • Tryptophan pyrrolase in tryptophan oxidation

Hemoglobin (Hb)

• Hemoglobin is the key molecule of oxygen transport
• It is the main constituent of RBCs and responsible for the red color of blood
• Hemoglobin has a large molecular weight and is electrically neutral
• Normal blood concentration of Hb is 12-16 gm/dL (female) and 14-18 gm/dL (male)
• Hemoglobin carries oxygen from lungs to tissues and carbon dioxide from tissues back to lungs

Hemoglobin Structure

• Hemoglobin molecule consists of four polypeptide chains: two alpha chains and two beta chains
• Each chain has a heme molecule containing a ferrous iron atom
• The protein portion of each chain is called globin
• Alpha and beta globin chains are very similar in structure, but distinct from each other
• Histidine residues in the globin chains form a fifth coordination bond with the heme iron ion

Types of Hemoglobin

• Embryonic Hb (a2e2)
• Fetal Hb (a2g2)
• Adult Hb (a2b2)

Functions of Hemoglobin

• Oxygen transport (oxy Hb)
• Carbon dioxide transport (carbamino Hb)
• CO transport (carboxy Hb)

Oxygen Binding to Hemoglobin

• Iron is displaced from one imidazol ring and one oxygen is attached instead
• Each Hb subunit contains a pocket for the heme that provides a non-polar environment for oxygen binding

Bohr Effect

• Decreased oxygen affinity of Hb in tissues due to high CO2 and H+ concentrations
• CO2 is transported as bicarbonate, formed by the enzyme carbonic anhydrase
• Protons generated from CO2 and water react with Hb, lowering its oxygen affinity
• In lungs, high oxygen concentration and low CO2 and H+ concentrations increase oxygen affinity of Hb

2,3-Diphosphoglycerate (2,3-DPG)

• A metabolite found in the anaerobic glycolysis pathway
• Binds to partially deoxygenated Hb, reducing its oxygen affinity
• Increases in response to chronic hypoxia or anemia
• Essential for the normal oxygen transport function of Hb

Carbon Monoxide (CO)

• A byproduct of incomplete combustion of fuels
• Has a 210 times greater affinity for Hb than oxygen
• Displaces oxygen from Hb, inhibiting oxygen transport
• Can cause carbon monoxide poisoning

Methemoglobin (MetHb)

• Formed when the iron of Hb is oxidized to the ferric state
• Cannot combine with oxygen, CO2, or CO
• Can be reduced back to Hb by MetHb reductase in the presence of NADPH
• Cyanide toxicity can be treated with sodium nitrite, which oxidizes some Hb to MetHb, which then reacts with CN- to form a non-toxic compound