MBB 222 Lecture Notes - Lecture 12: Fetal Hemoglobin, Sickle-Cell Disease, Myoglobin

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browncricket987

20 Dec 2018

School

Simon Fraser University

Department

Molec Biol & Biochem

Course

MBB 222

Professor

Adam Barlev

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Document Summary

Fetal hemoglobin has a lower affinity for 2,3-bpg. The globin gene expressed by fetuses differs from that expressed by human adults; fetal hemoglobin tetramers include two chains and two chains. Chains are 72% identical in amino acid sequence with the chain, but his143, which is critical in binding bpg, is substituted with a serine. This change removes positive charges from the bpg binding site and reduces the affinity of. Bpg for fetal hemoglobin, thereby increasing the oxygen-binding affinity. This allows oxygen to be effectively transferred from maternal to fetal rbcs, because the fetal hemoglobin could pick up o2 released by maternal hemoglobin. (50% saturation occurs at a lower po2 for fetal hemoglobin than for maternal hemoglobin. ) S2-val6 residue in one hbs tetramer can interact with the s-phe85 and s-leu88 residues in the other hbs tetramer. Understand the general structure of myoglobin (mb) and hemoglobin (hb), and how the heme binds to o2. Know the meaning of po2, p50, fractional saturation.

Related Questions

Normal adult hemoglobin is called Hemoglobin A (Hb A). Ninety-eight percent of adult hemoglobin is Hb A and 2% is Hb A2. There are other forms of hemoglobin. For example, the developing fetus has a different kind of hemoglobin than most normal adults. Fetal hemoglobin (Hb F) is synthesized beginning at the third month of gestation and continues up through birth. After the neonate is born, hemoglobin F synthesis declines (because synthesis of the (chain declines) and hemoglobin A is synthesized. By the time the baby is six months old, 98% of its hemoglobin is Hemoglobin A. There is also a mutant form of hemoglobin called Hemoglobin S, which is found in persons with the disease sickle cell anemia. The disease sickle cell anemia is one of the major health problems facing the African-American community. The World Health Organization estimates that 250,000 babies world wide are born with sickle cell anemia. Currently there is no cure. A person afflicted with sickle cell anemia has inherited a defective gene from each parent. The defective gene is the one coding for the Î²-chain. The amino acid at position 6 on each Î² chain has been mutated from a glutamate to a valine. Normal Î± chains have a decreased affinity for the mutated Î² chains; thus assembly of the HbS tetramer is more difficult. Red blood cells containing HbS form a sickle shape because the Hb S molecules polymerize. Hb S molecules are more likely to polymerize when in the deoxygenated T form than in the oxygenated R form. The polymerized Hb deforms the normal discoid shape of the red blood cells, producing a sickle-shaped cell. The sickle shaped red blood cells become trapped in capillaries and organs, depriving the victim of adequate oxygen supply and causing chronic pain and organ damage.

Glover, R. E., Ivy, E. D., Orringer, E. P., Maeda, H., and Mason, R. (1999) Molecular Pharmacology 55, pp. 1006-1010.

Huang, J., Hadimani, S. B., Rupon, J. W., Ballas, S. K., Kim-Shapiro, D. B., and S. Bruce King (2002) Biochemistry 41, pp. 2466-2474.

S. Bruce King (2003) J.Clin. Invest., 111, pp. 171-172.

1) Why do you think Hb S has higher tendency to polymerize compared to Hb A?

MBB 222 Lecture Notes - Lecture 12: Fetal Hemoglobin, Sickle-Cell Disease, Myoglobin

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