Lecture 13B - Things Affecting O2 Binding Curve of Hemoglobin

Question 1

The Bohr Effect

Answer 1

Increasing acidity shifts the Hb binding curve to the right (away from the Y-axis)

Question 2

Physiological Conditions Affecting pH of Blood

Answer 2

• Metabolism generates CO2 and lactic acid, especially from muscle cells
• Lactic acid dissociates in the blood and provides H+
• Metabolism increases, pH goes down, more O2 is released from oxygenated hemoglobin
• H+, CO2, and Cl- all shift shift oxygen binding curve to the right

Question 3

Where do “Bohr protons” bind?

Answer 3

• Bind in the T-state
• b chain C-terminal changes when O2 binds
• Hb can also bind CO2 at the N-termini, carbamate formation increases the acidity of the blood, more O2 released due to Bohr effect

Question 4

The BPG Effect

Answer 4

• 2,3-bis-phosphoglycerate
• Small triose (3 carbon sugar) found in the blood
• 5 negative charges
• BPG binds to Hb in the central region between the subunits, in the T-State
• Decreased O2 affinity with higher BPG, increased P50
• More BPG aids release of O2 from Hb

Question 5

Hb Variants

Answer 5

• All the globin genes are related
• Conservative changes don’t affect the charge on the amino acid, whereas non-conservative changes do
• over 1000 Hb variants known
• Some are asymptomatic, some cause serious problems

Question 6

Sickle-cell Hb (HbS)

Answer 6

• HbS has a single amino acid change in the b chain, Glutamic acid has been changed to valine
• Formation of long fibers in the T-state
• Val binds to hydrophobic pocket in a b chain of another Hb tetramer, only in the T-state
• Fiber formation occurs when Hb is deoxygenated, as pO2 decreases
• Fiber formation causes sickle cell shape to form in the capillaries