Protein structure, function, hemoglobin, and enzymes Flashcards
Name the four polypeptide chains found in normal adult hemoglobin (HbA).
two alpha and two beta
Name the four polypeptide chains found in normal fetal hemoglobin (HbF).
two alpha and two gamma
How many heme prosthetic groups are found in each hemoglobin? What is the O2 carrying capacity of one hemoglobin?
4 heme groups can carry 1 O2 each = 4 O2 molecules per hemoglobin.
Define the dissociation constant (Kd).
The partial pressure of O2 at which 50% of Hb O2-binding sites are saturated.
Kd = ([L][R]) / [LR]
When Kd for a particular receptor-substrate is very low, what does that mean?
It means the receptor-substrate affinity is very high!
Which chromosomes are Hb-alpha and Hb-beta genes found on?
Hb-alpha genes are found on chromosome 16.
Hb-beta genes are found on chromosome 11.
Where in the body does Hb synthesis occur beginning from conception? What is this process called and how does it happen?
Yolk sac from 0-6 weeks post-conception, then liver and spleen from 6 weeks to birth, then bone marrow onwards. This is called Hb switching and happens through developmental regulation of gene transcription (epigenetic changes).
How many copies of the Hb-alpha chain gene to people have? What about the Hb-beta chain gene? What is the clinical significance of this?
There are two Hb-alpha chain loci on chromosome 16 and each person has two copies of the chromosome - so 4 copies of the Hb-alpha gene.
There is only one Hb-beta chain gene on chromosome 11, so people only have 2 Hb-beta chain gene copies. Because of this, beta-thalassemias are more common. Also, the LCR on chromosome 11 can be mutated, resulting in thalassemia.
Sickle cell anemia (HbS disease) is a type of ________ anemia and is the most common hemoglobinopathy.
hemolytic anemia
What is the genetic defect involved in sickle cell disease?
It results from a missense mutation that changes a codon for glutamate to a codon for valine at AA #6 in the Hb-beta chain.
Does the HbS mutation have any effect on the ability of Hb to carry O2?
Nope
What is the mechanism for hemolysis in homozygotes with sickle cell disease?
deoxy-HbS tetramers assemble into long filaments that distort the round shape of RBCs, causing clogs in capillaries and eventual cell lysis.
What is the difference between cyanosis and pallor?
Cyanosis (blueish skin) means that blood is present but poorly oxygenated. Pallor means that blood is not reaching that area, which is indicative of anemia, such as hemolytic anemia in sickle cell disease.
What is methemoglobin? Can it carry O2? How does the body deal with it?
It is when the Fe2+ ion in heme gets oxidized to Fe3+. It can’t carry O2.
Methemoglobin reductase reduces it back.
What is Hb Hyde Park disease?
A disease in which a structural Hb defect restricts engagement with methemoglobin reductase –> cyanosis.
