Dear student

Please find below the answers to questions received during the lecture.
Don’t hesitate to send any question to me through your group leader.
Good luck

Links to videos :
1. Protein structures
https://www.youtube.com/watch?v=wvTv8TqWC48&t=394s
2. understanding sickle cell anemia
https://www.youtube.com/watch?v=wsykWqyXSKM
3. sickle and mechanism and drug design
https://www.google.com/search?sca_esv=563701320&q=voxelotor+and+sickle&tbm=vid&source=lnms&sa=X&ved=2ahUKEwj
OlqnXgZuBAxWYVqQEHa3TCdEQ0pQJegQIDhAB&biw=1920&bih=923&dpr=1#fpstate=ive&vld=cid:d13eda83,vid:gqx2xJI
qMGo

Be careful don’t confuse terminology

• RBC and sickled RBC and sickled hemoglobin (HbS)
• Normal adult hemoglobin

• Alpha helix : secondary structure

• Alpha globin chain: is a protein (subunit in HbA, HbF, HbA2)
• Beta sheet : secondary structure
• Beta globin chain: is a protein (subunit in HbA)
• Gamma globin chain: is a protein (subunit in HbF)

Does sickle cell makes rbc not flexible?

Sickle cell is sickle RBCs
Red blood cells are usually round and flexible, so they move easily through blood vessels. In sickle cell anemia, SOME red blood
cells are shaped like sickles or crescent moons. These sickle cells also become rigid and sticky, which can slow or block blood
flow. Decreased deformability and increased adhesion of sickle RBCs lead to blood vessel occlusion (vaso-occlusion) in SCD
patients.

Is there a text reference you’d recommend to review for this lecture?

Lippincott's Illustrated Reviews Biochemistry (check concept maps figures and summary). Chapter 2 and 3.

Is sickle cell anemia happen because gamma 2 ?

Short answer: No, gamma globin chains are not part of HbA (2alpha +2 beta) or HbS (2alpha +2 betas)
Explanation: HbA is the major hemoglobin in adult RBC. It is composed of two alpha globin chain and two beta globin chain.
HbS is composed of two alpha and two beta chains. however, beta has a substitution of one amino acid at position 6 causing
aggregation and fiber formation in deoxyHb. HbF is a minor Hb in adult. It is composed of two alpha and two gamma. Gamma
chains play a role in fiber formation or aggregate

Why is myoglobin in the muscles? In other words why is it different than the hemoglobin found in blood?
Myoglobin has a different O2 binding properties. They take their oxygen from Hb and store it for muscle needs during exercise.
Biomolecules serve different function depending on their properties.
For more information: https://byjus.com/biology/differentiate-between-hemoglobin-and-myoglobin/

Where do van der vaal’s forces play a role?

They are weak forces. They contribute to protein stability. The tertiary + quaternary structure are held by multiple types of bonds
and forces, including hydrophobic interactions, hydrogen bonding, disulfide bridge, ionic bonding, as well as van der Waals
forces.

What should we focus on from the lecture?

Check the objective of the lecture which include:
Level of protein structure and type of bond that hold various structure example in Hb and Myoglobin, characteristics of amino
acid with example, Hb and structural abnormalities in disease ( sickle and neurodegenerative )

Can alpha and beta be combined in one 3d dimension?

Yes
Many proteins contain both Alpha helices and Beta sheets, even though some contain just one type of secondary structure. If the
temperature of a protein environment is changed or when it is exposed to chemicals, they denatured. They will lose their three-
dimensional structure and they are non-functional.

Hemoglobin has 4 globin or 4 heme??

Yes,

How can we prevent or make a mutation?

This will be covered in genetic code and mutation lecture

If the medication for preventing the RBCs to become deoxy, then what is the point of the RBCs isn’t the idea is to carry
oxygen to the parts of the body?
Excellent question answer from a study published in 2021(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570057/)
1. Voxelotor therapy reduces sickling and increases hemoglobin, but oxygen delivery to tissues is offset by increased
hemoglobin O2 affinity.
2. Drugs that reduce sickling by increasing HbF or decreasing MCHC should be more effective than drugs that increase O2
affinity.

is proximal and distal exist in sickle cell rbc?

Yes, the first bind to iron in heme and second has a role in O2 binding
The iron in heme is itself attached on one side of the “heme pocket” to the amino acid residue histidine—the proximal histidine.
Another histidine is situated on the other side of the pocket. This second histidine is not directly linked to the ferrous atom and is
called the distal histidine. It stabilizes the oxygen in E7 (seventh residue of E helix).

I don’t understand the monomers of hemoglobin

Monomer is one unit. Unit in our lecture could be
• building block of protein: amino acid
• unit of structure: one subunit (one polypeptide chain) example: Hemoglobin is a tetramer composed of four chains of
polypeptides with a quaternary structure. Myoglobin is a monomeric protein made of a single polypeptide chain of
amino acids with a tertiary structure.