Proteins PBL Flashcards
What is sickle cell disease and what is the molecular abnormality that causes it?
A Point mutation that leads to the substitution of glutamate by valine in position 6 on the B-chain of haemoglobin
• Mishapen RBC HBA: Glutamate HBS: valine
• Unable to transport O2 efficiently as a result
How would you recognise that abnormal haemoglobin was present?
Electrophoresis of peptide fragments of HbA and HbS
• At pH 7, HbA migrates faster to the anode in electrophoresis (glutamate with negative charge)
Why does it result in fatigue?
Less SA to carry O2
Reduced RBC as they have a shorter life span (1/2 day)
Sickle cells can get blocked in the blood vessels
Why does the proportion of sickled cells increase on storage of the blood sample?
Only deoxygenated HbS forms polymers
Why is sickle cell disease associated with abnormal bilirubin clearance and why was melanies spleen enlarged?
Abnormally high Hb breakdown which causes BR formation and jaundice
Spleen overworked as breaking down RBC’s
Aspirin has been used as a treatment for sickle cell disease? Why?
Acetylation increases HB’s affinity for O2
Pushes Haem to stay Oxy for longer only deoxy deforms
Since sickle cell disease is genetically determined and was often fatal in the past, how do you account for its prevalence in certain populations?
Small gene pool
Isolated population
African geographic regions are most prone to malaria. The gene variant for sickle cell disease is related to malaria
Suggest a molecular abnormality which would cause this form of osteogenesis imperfecta (brittle bones)
A point mutation in the gene for pro-collagen precursor of A1 substitutes a cysteine codon in place of a glycine codon
What are the biochemical consequences of this change likely to be on the assembly of type 1 collagen?
Collagen structure more fragile
Sulfur bridges form which makes collagen structure more fragile (less flexible)
How might the predicted changes result in the skeletal deformities and brittle bones?
Sulfur bridges hold collagen fibres closer together making them more brittle
Two identical chains are held much more strongly Abnormal collagen structure defective mineralisation fragile bones
How would you recognise that an abnormal collagen was present?
Addition of reducing agent 2-mecraoethano which breaks the disulphide bonds
Why are only some of the a1(1) chains effected?
Heterozygous for condition
Heam
- Quaternary structure many multi- subunit globular proteins
- Most of the amino acids in haemoglobin form alpha helices, connected by short non-helical segments.
- Hydrogen bonds stabalise the helical sections inside the protein, causing attractions within the molecule, folding each polypeptide into a specific shape
- Haemaglobins quaternary structure comes from its four sub-units in roughly a tetrahedral arrangement
- Heme group consists of an Fe ion held in a heterocyclic ring, known as a porphyrin
- The Fe iron (site of O2 binding) co-ordinates with the 4 N atoms in the centre of the ring
- The Fe is bound covalently to the globular protein via the N atoms of the imidazole ring of the F8 histidine residue
- When O2 is not bound, a weakly bonded water molecule fills the site, forming a distorted octahedron
- Upon binding of O, Fe2+ 3+
- TETRAMER A2, B2