Case 8 Hemoglobin, the Oxygen Carrier Focus concept A mutation in the gene for h

Question

Case 8 Hemoglobin, the Oxygen Carrier Focus concept A mutation in the gene for hemoglobin results in an altered protein responsible for the disease sickle cell anemia. An understanding of the biochemistry of the disease may suggest possible treatments. uisite Hemoglobin structure and function concepts. Background Normal adult hemoglobin is called Hemoglobin A (Hb A). Ninety-eight percent of adult hemoglobin is Hb A and 2% is Hb A. There are other forms of hemoglobin. For example, the developing fetus has a different kind of hemoglobin than most normal adults. Fetal hemoglobin (or Hemoglobin F) consists of two a chains and two y chains, whereas adult hemoglobin (Hemoglobin A) consists of two a chains and two ß chains. Fetal hemoglobin 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 y chain declines) and hemoglobin A is synthesized (because synthesis of B chains begins). 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 discase 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. (Parents who are carriers of the sickle cell gene are hetcrozygous AS, whereas the person afflicted with sickle cell anemia is SS: non-carriers are designated AA.) The defective gene is the one coding for the ?-chain. The amino acid at position 6 on each ? chain has been mutated from a glutamate to a valine. Normal ? chains have a decreased affinity for the mutated B 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 nomal 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 In this case we will consider our patient, a 10-year-old black male child named Michael B., who was admitted to the hospital because he was experiencing severe chest pain. He had been hospitalized on several previous occasions for vaso-occlusive episodes that caused him to experience severe pain that could not be managed with non-prescription drugs such as ibuprofen. He was slightly jaundiced, short of breath and easily tired, and feverish. A chest x-ray was taken and was abnomal. An arterial blood sample showed a poz value of 6 kPa (normal is 10-13 kPa).

Explanation / Answer

a. Fetal hemoglobin has ability to inhibit the formation of hemoglobin aggregates within red blood cells which also contain hemoglobin S. Thus it helps in alleviating symptoms of sickle cell anemia.

b. Iron nitrosyl hemoglobin is a source of nitric oxide. Nitric oxide binds to guanylate cyclase enzyme which catalyzes synthesis of cgmp that induce transcription of fetal hemoglobin gene.

c.  Notric oxide binds to guanylate cyclase enzyme which catalyzes synthesis of cgmp that induce transcription of fetal hemoglobin gene.

Related Questions

Navigate

• Browse (All)
• Browse C
• Subjects

---

---

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.