Carbonic anhydrase

Question 1

Functions of carbonic anhydrase

Answer 1

1. Catalyses formation of bicarbonate from CO2
2. Catalyses hydration of aldehydes
3. Catalyses hydrolysis of certain esters

Question 2

Human carbonic anhydrase

Answer 2

CAII present in red blood cells which catalyses the reversible hydration of CO2
- Fundamental process in the removal of CO2 from metabolising sites

Question 3

Structure of CAII

Answer 3

• Metalloproteins contain 260 amino acids
• Zn2+ bound to three different histidine residues of imidazole group forming a tetrahedral coordination with a hydroxide ion or water molecule
• Zn2+ bound to water lowers pKa making water more likely to give up H
• OH- more nucleophilic than H2O allowing attack to C of CO2

Question 4

CAII and formation of bicarbonate

Answer 4

• Zinc bound OH- hydrogen bonds to glutamic acid and threonine residues on the protein chain
• Hydrophobic pocket next to Zn2+ captures CO2
• Activation of CO2 requires lewis acid attack to O and lewis base attack to C
• After release of bicarbonate, coordinated H2O needs to be deprotonated to generate active site

Question 5

What is glaucoma

Answer 5

Excessive intraocular pressure causes damage to the optic nerve and eventually leads to loss of vision
- Primary open angle glaucoma (POAG) is the most common form

Question 6

What does intraocular pressure?

Answer 6

• Certain amount required by eye to maintain its shape and preserve its shape

Question 7

Aqueous humour

Answer 7

• Fills the eyeball and creates pressure in the eye to give its shape

Question 8

Healthy eyes

Answer 8

• Fluid drains into bloodstream via trabecular meshwork at the same rate that its produced maintaining a constant pressure

Question 9

Patient suffering from glaucoma

Answer 9

• Blockage in trabecular meshwork
• Increases aqueous humour
• Pressure rises

Question 10

Carbonic anhydrase inhibitors in the treatment of glauoma

Answer 10

• Inhibits production of bicarbonate in the ciliary body of the eye resulting in decreases aqueous humour and lowers intraocular pressure

Question 11

Sulphonamide as inhibitors

Answer 11

ArSO2NH2 are strong inhibitors

• Displaces water molecule of carbonic anhydrase
• Coordinates to zinc atom via its nitrogen forming a tetrahedral complex
• Inhibition occurs as a result of substitution