Pentose Phosphate Pathway Dr. abdulhussein Algenabi

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.

One fate of G6P is the pentose pathway.

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 Nucleotide biosynthesis leading to: DNA ,RNA and Various cofactors (CoA, FAD, SAM, NAD+/NADP+). Serves as an entry into Glycolysis for both 5‐carbon & 6‐carbon sugars.

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

The nonoxidative phase of the pentose pathway This entails extensive carbon atom rearrangement. Transketolase requires the coenzyme thiamine pyrophosphate (TPP), the transaldolase does not.

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

Ingested ribose can enter the glycolytic pathway through the pentose pathway.

The cell needs both NADPH and ATP

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.

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.

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

People with the disorder are not normally anemic and display no evidence of the disease until the red cells are exposed to an oxidant or stress. Drugs that can precipitate this reaction: antimalarial agents sulfonamides (antibiotic) aspirin nonsteroidal antiinflammatory drugs (NSAIDs) nitrofurantoin quinidine quinine

None. The pathway is not designed to produce ATP What you have learned. 1. How many ATPs are produced by the oxidation of 1 glucose molecule in the pentose phosphate pathway? None. The pathway is not designed to produce ATP 2. How many ATPs are required to produce the final products of the pathway? None. The pathway does not require ATP 3. How many NADPHs are produced by oxidation of 3 glucose molecules in the pentose phosphate pathway? Six. Two for each glucose oxidized. 4. Is the pentose phosphate pathway considered anaerobic or aerobic? Anabolic or catabolic? Explain. Anaerobic and Anabolic. The pathway does not require oxygen. Therefore, it is an anaerobic pathway. Since it results in the synthesis of pentoses and NADPH, it must be considered primarily anabolic.