haemoglobin and molecular medicine Flashcards
Describe the structure of haemoglobin.
Haemoglobin a tetramer with an2β2 structure, where the αunit contains 141 amino acids and the βunit contains 146 amino acids.
What is the primary difference the α and β subunits of haemoglobin?
The primary sequences of α and β subunits differ, but their tertiary structure is the same.
How does foetal haemoglobin differ from adult haemoglobin?
Foetal haemoglobin (α2γ2) has a different subunit composition compared to adult haemoglobin, and it allows for efficient oxygen exchange in the foetal circulation.
Define cooperative binding of oxygen in haemoglobin.
Cooperative binding of oxygen in haemoglobin refers to the phenomenon where the binding of one oxygen molecule enhances the affinity for subsequent oxygen molecules.
Who determined that sickle cell disease was caused by an abnormality in haemoglobin?
Linus Pauling, from CalTech, Pasadena, determined that sickle cell disease was caused by an abnormality in haemoglobin.
What was the contribution of Vernon Ingram in the study of sickle cell disease?
Vernon Ingram, from MIT, Boston, determined the mutation responsible for sickle cell disease.
Describe the role of Max Perutz in understanding sickle cell disease.
Max Perutz, from Cambridge, provided a structural explanation for the effect of mutation in sickle cell disease.
Who was the first person to clearly describe a link between molecular and clinical defects in human disease?
David Weatherall, from Oxford, was the first person to clearly describe a link between molecular and clinical defects in human disease.
What technique did Maud Menten and colleagues use to distinguish between haemoglobin variants in 1944?
Maud Menten and colleagues used sedimentation and electrophoresis to distinguish between haemoglobin variants in 1944.
Describe the contribution of Linus Pauling in the study of sickle cell disease.
Linus Pauling determined that sickle cell disease was caused by an abnormality in hemoglobin
What did Vernon Ingram determine regarding sickle cell disease?
Vernon Ingram determined the mutation in sickle cell disease.
Define the significance of Max Perutz’s work in relation to sickle cell disease.
Max Perutz provided a structural explanation for the effect of mutation in sickle cell disease.
How did David Weatherall contribute to the understanding of human diseases?
David Weatherall was the first person to clearly describe a link between molecular and clinical defects in human disease.
What was the key finding regarding the electrophoretic mobility of hemoglobin in sickle cell patients?
The sickle cell hemoglobin was more positively charged compared to normal hemoglobin.
Describe the observation made about the hemoglobin of healthy individuals of Caucasian and African descent.
Healthy individuals of Caucasian and African descent were shown to have ‘indistinguishable’ hemoglobin.
What was the significance of the difference observed in the globins of hemoglobin from normal and sickle cell patients?
It was the first demonstration that a disease could be caused by an abnormality in a protein.
Describe the experiment conducted by Vernon Ingram involving haemoglobin and trypsin digestion.
Vernon Ingram digested haemoglobin into fragments using trypsin and analyzed them through 2-dimensional electrophoresis.
Define the small change observed by Vernon Ingram in sickle cell haemoglobin.
The change consisted of the replacement of one glutamic acid by valine in nearly 300 amino acids.
How did Vernon Ingram demonstrate the difference between haemoglobin A and haemoglobin S at the peptide level?
He found one peptide that was positively charged in haemoglobin S but uncharged in haemoglobin A.
Do you know the error Vernon Ingram made in the N-terminus sequence of haemoglobin?
He mistakenly listed Valine instead of Glutamic acid in the sequence.
Describe the genetic code changes identified by Vernon Ingram related to sickle cell mutation.
In sickle cell mutation, Glutamic acid (GAG) is replaced by Valine (GTG) in the genetic code.
What contribution did Vernon Ingram make to the field of molecular medicine?
He is considered the Father of Molecular Medicine for his groundbreaking work on sickle cell mutation.
Explain the significance of Vernon Ingram’s discovery regarding the sickle cell mutation in the β-globin chain.
He demonstrated that the sickle cell mutation was specific to the β-globin chain and not the α-globin chain.
What hypothesis did Vernon Ingram contribute to with his work?
He contributed to the ‘one gene – one protein’ hypothesis, providing the first real proof.
