Question

In human hemoglobin, distal histidine residues were mutated to leucine, resulting to a two fold decrease in oxygen affinity. a) Do you expect a cooperative oxygen binding? Explain your reasoning. No because cooperative oxygen binding is when a substrate binds to an enzymatice unit. Due to the mutation on Luecine, Luecine can’t stabilize the oxygen that was bound. b) The wild type hemoglobin has pO250 = 26 Torr. What is p50 value for mutated hemoglobin? In Excels software , draw an oxygen binding curve for mutated hemoglobin, the Hill coefficient is 2.8. Use the range of pO2 from 0 Torr to 200 Torr with an increment of 20 Torr

Answer 1

Cooperativity in oxygen binding to hemoglobin is likely to be affected when the distal histidine is mutated to leucine, potentially altering the S-shaped oxygen dissociation curve and resulting in a decreased oxygen affinity. The new p50 value for the mutated hemoglobin could be approximately 52 Torr, assuming a simplistic two-fold decrease in oxygen affinity.

Step-by-step explanation:

The concept of cooperativity is crucial to understanding hemoglobin's function. When one molecule of oxygen binds to a hemoglobin subunit, it increases the affinity of the remaining subunits for oxygen, resulting in an S-shaped oxygen dissociation curve. This characteristic allows for efficient oxygen loading in the lungs and offloading at the tissues. Upon mutating distal histidine to leucine, the cooperativity may be affected since distal histidine plays a role in stabilizing bound oxygen. Therefore, although cooperativity may still occur as it is a property of the tetrameric structure of hemoglobin, the mutation could lead to a decreased oxygen affinity, reflected in altered oxygen binding dynamics.

In response to the mutation, if the oxygen affinity of hemoglobin has decreased by a factor of two, the pO2 at which hemoglobin is 50% saturated (p50) would likely increase. Calculating the exact value of the new p50 cannot be done without additional information, such as the specific nature of the cooperativity curve alterations. A doubling of p50 value is a simplified assumption based on a two-fold decrease in affinity, suggesting that the new p50 for the mutated hemoglobin would be around 52 Torr (double of the wild-type p50 of 26 Torr).