Pentose Phosphate Pathway

• Pentose phosphate pathway undergoes three stages; NADPH is produced, pentoses undergo isomerization, and glycolytic intermediates are recovered
• The pathway provides NADPH for reductive biosynthesis, and R5P for nucleotide synthesis
• ATP in terms of its exergonic cleavage is coupled to many endergonic cell functions
• Many endergonic reactions, notably the reductive biosynthesis of fatty acids and cholesterol require NADPH and ATP
• Cells would capture free energy of metabolite oxidation as NADH to synthesize ATP in oxidative phosphorylation
• Cells capture free energy as NADPH for reductive biosynthesis
• NADPH can be generated by the hexose monophosphate shunt (pentose phosphate pathway)
• 30% of the glucose oxidation in the liver happens in the pentose phosphate pathway than glycolysis
• Dehydrogenases oxidizes the reaction while the enzyme produces a proton and NADPH
• Reaction 1 is where Glucose 6 phosphate is oxidized by glucose 6 phosphate dehydrogenase with a cofactor NADP+ which transfers a hydride ion to NADPH forming 6 phosphoglucono delta lactone
• Reaction 2 is where 6 Phosphogluconolactonase and a cofactor of H2O opens the ring of 6 phosphoglucono delta lactone to form 6 phospho gluconate and a hydrogen ion
• Reaction 3 is where 6 phosphogluconate dehydrogenase oxidatively carboxylated 6 phosphogluconate to produce ribulose 5 phosphate, NADPH, and CO2
• Stage 1 involves oxidative reactions with glucose - 6 - phosphate - dehydrogenase and NADP+, which yield NADPH and H+ and ribulose-5-phosphate
• The overall reaction in stage 1 involves an irreversible reaction

  
• Reactions 4 and 5 are where ribulose-5-phosphate is either isomerized or epimerized to ribose-5-phosphate or xylulose-5-phosphate respectively
• The enzyme that isomerates Ru5P is ribulose-5-phosphate-isomerase
• The enzyme that epimerizes Ru5P is ribulose-5-phosphate-epimerase
• The overall reaction in stage 2 involves a reversible reaction

  
• In stage 3, a series of C-C bonds cleavage and formation reactions that convert two molecules of Xu5P and one molecule of R5P to two molecules of F6P and one molecule of GAP
• Step 6 is where Xylulose-5-phosphate with Ribose-5-phosphate accepts a 2 carbon ketol group from Xylulose 5-phosphate producing Sedoheptulose-7-phosphate and GAP
• Step 7 is where the S7P transfers its ketol and adjacent hydroxyl group to GAP by transaldolase forming F6P and Erythrose-4-phosphate
• In step 8, Xu5P donates its 2 carbon ketol group to E4P by a transketolase forming F6P and GAP
• The sum of reactions in Stage 3 is 2Xu5P + R5P <-> 2F6P + GAP
• The overall reactions of pentose phosphate pathway is $3 G6P +$$6NADH +$$3H_2O <-> 2F6P +$$3GAP +$$6H^+$$+$$6NADPH +$$3CO_2$
• G6P can be produced from either the hexokinase of glucose, or from the glycogen breakdown
• The first three reactions of the pentose phosphate pathway are involved in the NADPH production
• 6-Phosphogluconolactonase increases the rate of hydrolysis of 6 phosphoglucono delta lactone to 6 phosphogluconate
• 6-Phosphogluconate dehydrogenase catalyzes the oxidative decarboxylation of 6-phosphogluconate to Ru5p, NADPH and CO2
• The relative amounts of Ribose 5 Phosphate (R5P) and Xylulose 5 Phosphate (Xu5P) produced from Ru5P depend on the needs of the cell
• NADH is oxidized by the respiratory chain to generate ATP
• NADPH serves as a reductant in biosynthetic processes
• NADPH and NADH are not interchangeable
• PPP would address the physiological need of an organism such as ATP, NADPH and ribose and other glycolytic products
• NADH is an adenylic acid that is phosphorylated at the carbon 2 of sugar
• NADPH has no positive charge and it is replaced it with hydrogen
• NAD+ is the more predominant species than NADH, which favors metabolite oxidation
• NADPH is the more predominant species than NADP+ near a ratio of 0.01, which favors reductive biosynthesis
• Majority of tissues in PPP is where lipids are synthesized except of the red blood cells which requires the maintenance of reduced glutathione
• The flux of the pathway would depend on the need of the organism because this pathway is closely linked to glycolysis
• 3 Molecules of Glucose 6 phosphate are needed to produce 6 NADPH, and 3 Ribulose 5 Phosphate in step 1