G6PD deficiency risk factors:
Most people do not have any symptoms in the absence of G6PD, meaning they are asymptomatic. However, the symptoms are more common in men than in women. The symptoms of G6PD deficiency are as follows:
- Hemolysis (is the breakdown of red blood cells)
- Neonatal jaundice
- Reaction to eating fava beans
- Reactions to certain drugs (described above)
- Diabetic ketoacidosis
- Red or brown urine (hemoglobinuria)
- Kidney failure
- Reaction to exposure to certain chemical compounds such as naphthalene
Cause of G6PD deficiency:
Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that acts as a catalyst in the first step of the pentose phosphate pathway and produces NADPH . NADPH is essential for many biosynthetic pathways. NADPH protects cells from hydrogen peroxide (H2O2) and superoxide free radicals. Free radicals are highly reactive active oxidants that are produced as metabolic byproducts and are also produced through the activity of drugs such as Primaquine or Divicin.
During normal detoxification, hydrogen peroxide (H2O2) is converted to H2O by the action of toxic glutathione and glutathione peroxidase and the oxidized glutathione returns to the decomposed state through the enzyme glutathione reductase and NADPH. Toxic glutathione protects cells by destroying hydrogen peroxide and hydroxyl free radicals. If this process is interrupted, these free radicals will cause severe damage to the cells. Such as cell destruction, lipid peroxidation, erythrocyte membrane rupture, oxidation and damage of proteins and DNA etc.
This process occurs in a normal healthy body. But individuals with G6PD enzyme deficiency cannot produce NADPH and therefore the detoxification of H2O2 is hindered. This results in cellular damage, lipid peroxidation, breaks down erythrocyte membranes, and proteins and DNA oxidize.
Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is a congenital defect that predicts red blood cell breakdown. Deficiency of this enzyme causes premature breakdown of red blood cells. This destruction of RBC is called hemolytic anemia. This problem can be caused by eating fava beans or by inhaling pollen from fava beans.
Why Fava beans?
Fava beans have been known since ancient times as an important food source in the Mediterranean and the Middle East. However, Pythagoras , the great philosopher and mathematician, forbade his followers to eat fava beans because people in his time would get sick from eating fava beans. Fava beans cause a disorder called Favism which makes many people sick at that time. Nowadays, researchers have identified chemical substances known as vicin and convicin present in Fava beans that trigger hemolytic anemia in people with G6PD deficiency .
What is Favism?
Favism is a disorder characterized by hemolytic anemia or red blood cell separation. It is an X-linked recessive disorder that causes a deficiency in the enzyme glucose-6-phosphate dehydrogenase. Hemolytic anemia can be caused by various infections, stress or foods like fava beans. In Favism, erythrocytes begin to release free hemoglobin into the blood 24 to 48 hours after eating beans. Jaundice and sometimes kidney failure. Most people with G6PD’s favism are asymptomatic. Symptoms may occur only when there is a combination of G6PD deficiency and some environmental factors. Most of the people who show symptoms due to X-linked inheritance are male. Favism can also be triggered by certain malarial drugs.
How do anti-malarial drugs trigger Favism?
In vitro studies have shown that growth of one type of malaria parasite Plasmodium falciparum is inhibited in individuals with G6PD deficiency. This is because the parasite is very sensitive to oxidative damage and it dies due to oxidative stress. We already know that G6PD deficient human hosts produce oxidative stress due to free radicals which prevents the parasite from surviving. But in the normal body, anti-malarial drugs are injected to kill the malaria parasite. Anti -malarial drugs such as primaquine, divisin cause oxidative stress in parasites and prevent malaria. Thus, anti-malarial drugs have the potential to trigger fascism by causing oxidative stress.
How to control Favism :
About 400 million people worldwide have this condition. It is very common in Africa, Asia, the Mediterranean and parts of the Middle East. Men are more affected than women. Since it is a congenital defect, it cannot be cured. Thus, infected people must avoid dietary triggers such as fava beans. Fava beans are very common and are used in many foods or as flour. Falafel is a common food that contains fava beans. Fava beans are also used as a filter in meat and other foods. So Fava beans should be excluded from the diet. Some other things like sulfa drugs , anti-malarial drugs, divicin, herbicide etc. should be avoided. Some medications for infections should also be avoided.
Try to answer this Ques: Discuss the role of NADPH and glutathione in protecting cell against highly oxygen derivatives.