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Pentose Phosphate Pathway

Pentose Phosphate Pathway. Dr. Sooad Al-Daihan Biochemistry department. Overview. The pentose phosphate pathway is also called Hexose Monophosphate Shunt or Phosphogluconate Pathway .

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Pentose Phosphate Pathway

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  1. Pentose Phosphate Pathway Dr. Sooad Al-Daihan Biochemistry department

  2. Overview • The pentose phosphate pathway is also called Hexose Monophosphate Shunt or Phosphogluconate Pathway. • It is an alternate route for the oxidation of glucose without direct consumption or generation of ATP. • It takes place entirely in the cytoplasm.

  3. Importance of pentose phosphate pathway : • Generation of NADPH • mainly used for reductive synthesis of fatty acids, cholesterol and steroid hormones. • hydroxylation reaction in metabolism of phenylalanine and tryptophan. • production of reduced glutathione in erythrocytes and other cells. • Production of ribose residues • used for nucleotide, nucleic acid , and coenzyme biosynthesis • Serves as an entry into Glycolysis for both 5‐carbon & 6‐carbon sugars.

  4. The PPP is divided into two phases • Oxidative non-reversible phase -generates NAPDH -Glucose 6-p undergoes dehydrogenation and decarboxylation to give a pentose, ribulose 5-p, which is converted to its isomer, D-ribose 5-p. -Overall equation of 1st phase: Glucose 6-p + 2 NADP++ H2O  ribose 5-p + CO2 + 2 NADPH + 2 H+ • Non-oxidative reversible phase -ribose 5‐P is converted back to Glucose 6-p by a series of reactions involving especially two enzymes • Transketolase :Transfer of the 2‐C fragment • Transaldolase :Transfer of the 3‐C fragment

  5. Summary Xylulose-5-p Sedoheptulose-7-p Ribose-5-p Erythrose-4-p Fructose-6-p Glyceraldehyde-3-p

  6. Importance of PPP in RBC • 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 PPP is responsible for maintaining high levels of NADPH in red blood cells for use as a reductant in the glutathione reductase reaction.

  7. Regulation of the pentose phosphate pathway • Glucose-6-P dehydrogenase (Rate Limiting Reaction) is controlled by: • Allosteric Regulation • -Feedback inhibited by NADPH • Inducible enzyme • -The synthesis of glucose 6-phosphate dehydrogenase is induced by the increased insulin/glucagon ratio after a high carbohydrate meal.

  8. Glucose-6-phosphate dehydrogenase deficiency causes hemolytic anemia • 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. *toxic ingredient of fava beans

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