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LET'S TALK LIFE-SCIENCE BIOCHEMISTRY

Suraj Prakash Sharma | Ekta Chotia

PENTOSE PHOSPHATE PATHWAY
137

19.3.      Regulation

The first step of the phosphopentose pathway is the irreversible committed step. This reaction is catalyzed by glucose-6-phosphate dehydrogenase. This step is of course allosterically regulated. The product of this reaction NADPH is a strong inhibitor. So when the cytosol concentration of NADPH is high, the enzyme’s activity is low. It is also allosterically regulated by fatty acid acyl esters of coenzyme A. The transcription of the gene for this enzyme is under hormonal regulation.

When erythrocytes are exposed to chemicals that generate high levels of superoxide radicals, GSH (Reduced Glutathione) is required to reduce these damaging compounds Glutathione Peroxidase catalyzes degradation of organic hydroperoxides by reduction, as two glutathione molecules are oxidized to a disulfide GSSG The Pentose phosphate pathway is responsible for maintaining high levels of NADPH in red blood cells for use as a reductant in the glutathione reductase reaction. Regulation of the G6PD activity controls flux through the glycolytic pathway and pentose phosphate pathways.

The synthesis of glucose 6?phosphate dehydrogenase is induced by the increased insulin/glucagon ratio after a high carbohydrate meal Insulin, which secreted in response to hyperglycemia, induces the synthesis of G6P dehydrogenase and 6?phosphogluconate dehydrogenas increasing the rate of glucose oxidation by pentose phosphate pathway ring fasting

Mutations present in some populations causes a deficiency in glucose 6?phosphate dehydrogenase, with consequent impairment of NADPH production. Detoxification of H2O2 is inhibited, and cellular damage results ? lipid peroxidation leads to erythrocyte membrane breakdown and hemolytic anemia.

Most G6PD?deficient individuals are asymptomatic ? only in combination with certain environmental factors (sulfa antibiotics, herbicides, antimalarials, divicine) do clinical manifestations occur.

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