Mutant hemoglobin

Q.26.3 The difference between normal hemoglobin A and the sickle-cell hemoglobin mutant protein is a single amino acid replacement of glutamate with valine in the fi chains. (Each hemoglobin molecule is composed of 2a and 2fi chains). The mobility of these two proteins can be measured as +0.3 X 10 m2/s - V and —0.2 x W m /s - V. 

Studies of hemoglobin mutants where the nonpolar distal residue jSValEll (—CH(CH3)2) is replaced by alanine (—CH3), isoleucine (—CH(CH3)CH2CH3), and leucine (—CH2CH(CH3)2) reveal that this valine offers steric hindrance to oxygen binding in the T state. 

NUMEROUS MUTANT HUMAN HEMOGLOBINS HAVE BEEN IDENTIFIED... 

Certain mutant hemoglobins are common in many populations, and a patient may inherit more than one type. Hemoglobin disorders thus present a complex pattern of clinical phenotypes. The use of DNA probes for their diagnosis is considered in Chapter 40. 

SCA is the homozygous (HbSS) state of SCD in which individuals inherit the mutant hemoglobin gene (HbS) from both parents. The progeny of two carriers will have a 25% probability of having SCD and a 50% risk of being a carrier themselves (Fig. 65-1). P-Thalassemia can be found in conjunction with HbS. Patients with HbSS and HbSjf- thalassemia do not... 

Restriction analysis can be used to detect sickle cell disease prenatally, since the DNA of all cells, including amniotic cells, carries the mutant DNA. It is much more difficult to obtain fetal blood for the analysis of the mutant hemoglobin A P-chain. Furthermore, fetal blood is composed mostly of fetal hemoglobin, sinee-hemoglobin A is made later in development. 

It has been proposed that a major source of oxygen radicals in sickle erythrocytes is mutant hemoglobin HbS. However, although HbS showed an accelerated autoxidation rate under in vitro conditions, its in vivo oxidative activity was not determined. Sheng et al. [401] suggested that the observed oxidation rate of HbS is exaggerated by adventitious iron. Dias-Da-Motta et al. [402] proposed that another source of enhanced superoxide production in sickle cells are monocytes in contrast, there is no difference in superoxide release by sickle... 

Deoxygenated sickle cell hemoglobin (deoxyHbS), the j8-Glu-6-Val point mutant form of adult hemoglobin, appears to obey the following empirical rate law for nucleation of polymerization ... 

Sickle cell anemia is caused by synthesis of a mutant form of hemoglobin, hemoglobin 5 or HbS), in which a glutamic acid at position 6 of the hemoglobin (3 subunit is replaced by valine. 

The answer is B. Sickle cell anemia is caused by inheriting two copies of a mutant P glo-bin gene that leads to synthesis of sickle hemoglobin, HbS. A severe case of sickle cell anemia would most likely have demonstrated symptoms and been diagnosed before the age of 6. However, he may only be a carrier, with one copy each of normal P-globin and one of the sickle allele, a condition called sickle cell trait. Nevertheless, the patient s... 

The genetic change that produced the mutant hemoglobin in sickle cell anemia can be classified as which type of mutation ... 

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