Question

Why Pythagoras wouldn’t eat Falafel: A story about Glucose-6-Phosphate Dehydrogenase (G6PD)

Deficiency Fava beans, an ingredient of falafel, have been an important food source in the Mediterranean and Middle East since antiquity. The Greek philosopher and mathematician Pythagoras prohibited his followers from dining on fava beans, perhaps because they made many people sick with a, sometimes fatal, condition called favism. In favism, erythrocytes begin to lyse 24-48hrs after ingestion of the beans, releasing free haemoglobin into the blood. Jaundice and sometimes kidney failure can result. These symptoms have a genetic basis – G6PD deficiency. Most G6PD deficient individuals are asymptomatic with only a combination of genetic deficiency and environmental factors producing severe clinical manifestations.

a) What biochemical process is G6PD involved in?

b) How is this related to cell protection from H2O2 and superoxide free radicals?

c) The natural product divicine is a component of fava beans. What metabolic byproduct(s) does it cause and how would this cause toxicity in G6PD deficient individuals?

d) Explain, with particular reference to cellular damage, why the lack of G6PD in certain individuals may result in serious illness or death.

The geographic distribution of G6PD deficiency is instructive. Frequencies as high as 25% occur in tropical Africa, parts of the Middle East and Southeast Asia, areas where malaria is most prevalent. In addition, in vitro studies of one malaria parasite, Plasmodium falciparum, show that its’ growth is inhibited in G6PD-deficient erythrocytes. The parasite is very sensitive to levels of oxidative stress that are otherwise tolerable to a G6PD-deficient human host.

e) Comment on the most likely mechanism by which Plasmodium falciparum is affected by oxidative stress.

f) Could fava beans be used as a natural antimalarial drug?

g) What were the possible repercussions on Pythagoras’s followers who did not consume falafel?

Answer 1

a) What biochemical process is G6PD involved in?

G6PD involved AND catalyzes the first step in the pentose phosphate pathway. IT IS A METABOLIC PATHWAY SIMILAR TO GLYCOLYSIS.

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b) How is this related to cell protection from H2O2 and superoxide free radicals?

a) the pentose phosphate pathway produces NADPH.

b) This reductant, protects cells from oxidative damage by hydrogen peroxide (H2O2) and superoxide free radicals.

c) The highly reactive oxidants generated as metabolic byproducts and through the actions of drugs such as primaquine and natural products such as divicine—the toxic ingredient of fava beans.

d) During normal detoxification, H2O2 is converted to H2O by reduced glutathione and glutathione peroxidase.

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c) The natural product divicine is a component of fava beans. What metabolic byproduct(s) does it cause and how would this cause toxicity in G6PD deficient individuals?

In G6PD-deficient individuals,

A) the NADPH production is diminished and detoxification of H2O2 is inhibited. Cellular damage results:

B) lipid peroxidation leading to breakdown of erythrocyte membranes and oxidation of proteins and DNA.

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d) Explain, with particular reference to cellular damage, why the lack of G6PD in certain individuals may result in serious illness or death.

Red blood cells, which carry oxygen, don't get enough energy when G6PD is lacking may result in serious illness or death.

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e) Comment on the most likely mechanism by which Plasmodium falciparum is affected by oxidative stress.

A) Plasmodium falciparum, is inhibited in G6PD-deficient erythrocytes.

B) The parasite is very sensitive to oxidative damage and is killed by a level of oxidative stress that is tolerable to a G6PD-deficient human host.

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f) Could fava beans be used as a natural antimalarial drug?

NO, Fava beans HAS NATURAL OXIDATANT WHICH DAMAGES THE RBC CELLS IN G6PD deficient individuals

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g) What were the possible repercussions on Pythagoras’s followers who did not consume falafel?

By refusing to eat falafel, many Pythagoreans with normal G6PD activity may have unwittingly increased their risk of malaria!

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