Why Pythagoras Wouldnt Eat Falafel Glucose 6Phosphate Dehydrogenase 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 make many people sick with a condition called favism, which can be fatal. In favism, erythrocytes begin to lyse 24 to 48 hours after ingestion of the beans, releasing free hemoglobin into the blood. Jaundice and sometimes kidney failure can result. Similar symptoms can occur with ingestion of the antimalarial drug primaquine or of sulfa antibiotics or following exposure to certain herbicides. These symptoms have a genetic basis: glucose 6-phosphate dehydrogenase (G6PD) deficiency, which affects about 400 million people. Most G6PD-deficient individuals are asymptomatic; only the combination of G6PD deficiency and certain environmental factors produces the clinical manifestations.

G6PD catalyzes the first step in the pentose phosphate pathway (see Fig. 14-21), which produces NADPH. This reductant, essential in many biosyn-thetic pathways, also protects cells from oxidative damage by hydrogen peroxide (H2O2) and superoxide free radicals, highly reactive oxidants generated as metabolic byproducts and through the actions of drugs such as primaquine and natural products such as di-vicine—the toxic ingredient of fava beans. During normal detoxification, H2O2 is converted to H2O by reduced glutathione and glutathione peroxidase, and the oxidized glutathione is converted back to the reduced form by glutathione reductase and NADPH (Fig. 1). H2O2 is also broken down to H2O and O2 by catalase, which also requires NADPH. In G6PD-deficient individuals, the NADPH production is diminished and detoxification of H2O2 is inhibited. Cellular damage results: lipid peroxidation leading to breakdown of erythrocyte membranes and oxidation of proteins and DNA.

FIGURE 1 Role of NADPH and glutathione in protecting cells against highly reactive oxygen derivatives. Reduced glutathione (GSH) protects the cell by destroying hydrogen peroxide and hy-droxyl free radicals. Regeneration of GSH from its oxidized form (GSSG) requires the NADPH produced in the glucose 6-phosphate dehydrogenase reaction.

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 to such epidemiological observations, in vitro studies show that growth of one malaria parasite, Plas-modiumfalciparum, is inhibited in G6PD-deficient erythrocytes. The parasite is very sensitive to oxida-tive damage and is killed by a level of oxidative stress that is tolerable to a G6PD-deficient human host. Because the advantage of resistance to malaria balances the disadvantage of lowered resistance to oxidative damage, natural selection sustains the G6PD-deficient genotype in human populations where malaria is prevalent. Only under overwhelming oxidative stress, caused by drugs, herbicides, or divicine, does G6PD deficiency cause serious medical problems.

An antimalarial drug such as primaquine is believed to act by causing oxidative stress to the parasite. It is ironic that antimalarial drugs can cause illness through the same biochemical mechanism that provides resistance to malaria. Divicine also acts as an antimalarial drug, and ingestion of fava beans may protect against malaria. By refusing to eat falafel, many Pythagoreans with normal G6PD activity may have unwittingly increased their risk of malaria!

Superoxide radical

Hydrogen peroxide

H2O^

Mitochondrial respiration, ionizing radiation, sulfa drugs, herbicides, antimalarials, divicine glutathione peroxidase

Hydroxyl free radical

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  • terry
    Why pythagoras wouldnt eat falafel?
    8 years ago
  • Fallon
    Why pythagoras would not eat falafe?
    2 years ago
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    Why pythagoras wont eat falafet?
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  • Damiana
    Why pathagoras would not eat falafel?
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