The X-linked allele for glucose 6-phosphate dehydrogenase deficiency (Gd-) also confers resistance to malaria. You make...

The X-linked allele for glucose 6-phosphate dehydrogenase deficiency (Gd^-) also confers resistance to malaria. You make a microscopic examination of the blood of a woman suffering from malaria. You observe that about one-half of the cells contain parasites, whereas one-half of the cells are unaffected. Explain this result.

Expert Solution

G6PD is an important enzyme in red blood cells (erythrocytes), the host cells for Plasmodium falciparum, the parasite that causes the most severe form of malaria. G6PD deficiency is associated with protection against malaria.

Mechanisms: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an incomplete hereditary X-linked hemolytic disease.G6PD catalyzes the reaction in the pentose phosphate pathway that generates reduced form of NADPH, which is in turn responsible for glutathione (GSH) homeostasis.GSH is an antioxidant, and together, these processes make cells more able to resist and control oxidative stress. Inability of the erythrocytes to maintain GSH homeostasis results in oxidative stress and affects the integrity of the RBCs, giving rise to hemolysis. Optimum RBC redox status is required by malaria parasites for their survival, replication, and development6. This factor is diminished in G6PD deficient RBCs, supporting the protection hypothesis.

Because females have two X chromosomes, traits on the X chromosome such as a mutated gene may be “masked” by the normal gene on the other X chromosome. This is known as random X--chromosome inactivation. Basically, in each cell of the body one X chromosome is active and one is turned off or “silenced.” This occurs randomly and generally happens as a 50-50 split. However, in some instances, females may have favorable X-inactivation, in which the affected X chromosome is silenced in most of the cells. In such cases, they may have sufficient G6PD enzyme activity as to avoid developing symptoms even in the presence of triggering factors. In other cases, females may have unfavorable X-inactivation, in which the unaffected X chromosome is silenced in most of the cells.

This clearly explains that due to random X chromosome inactivation in female due to 2 X chromosome, half of the cells can be deficient for G6PD while rest are not deficient.

So those cells which are deficient in G6PD will not show parasite while those with normal G6PD will show parasite.

Thank you:)

gladiator answered 2 years ago

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