Lecture 6 Flashcards
What is HbF? How does it differ with HbA?
HbF is the foetal version of haemoglobin, it has a greater affinity for oxygen than adult haemoglobin because it binds less strongly with 2,3-biphosphoglycerate, this is due to its subunit strucutre being 2 alpha and 2 gamma subunits rather than the adult two alpha two beta (Ser at pos 143 rather than His for HbA).
What is the general trend for globin subunit amount in an individual over time?
Alpha and gamma starts high (roughly 50%) then alpha increases slightly to 50% and gamma starts to lower as beta rises from its low levels to roughly 50% (the largest changes occur slightly prior to and after birth).
Epsilon and zeta subunits also exist during early development but are quickly replaced. Delta subunits start to be produced after birth in small amounts.
Where are the two main globin subunit family genes found?
Alpha: chromosome 16, beta: chromosome 11.
What kind of problems in the subunits can lead to blood problems?
Transcription/mRNA processing defects causing failures of globin protein synthesis, point mutations in DNA resulting in amino acid changes, or truncation of globin protein products and other point mutations that lead to instability of the tense or relaxed conformation.
What is HbS? What is the change?
Sickle cell anemia, amino acid 6 in the beta subunit (A3) is normally the polar glutamic acid but is replaced with valine (non polar), this makes the valine likely to try fit into non polar gaps (Phe 85 and Leu 88) in neighbouring units, making them likely to crystallise.
What is HbM? What is the change?
Any haemoglobins with iron in the 3+ (ferric state), an example is substitution of E7 His with Tyr, causing the F8 connection to be lost and reformed with Tyr (allowing Fe into the 3+ state).
Another is 67 val being replaced with glutamate, the side chain of which has a negative charge (COO-) and stabilises the 3+ state.
HbM moleculese remain in the tense state, reducing the affinity for oxygen.
Where do most globin mutations occur?
In the beta subunit.
What is Hb Christchurch? What is the change?
This occurs in the beta subunit on E15, this is normally phenylaline (large and non polar) but is replaced with serine (small and polar), this leads to slight destabilisation of the haem (not as serious as other mutations).
What is HbC? What is the change?
A mutation common in west Africa, a change on A3, glutamic acid (polar and negative charge) is replaced with lysine (larger, basic, positive charge). This mutation helps reduce the ability of malaria to produce knobs on the surface of red blood cells, lowering blockages caused by malaria.
