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PENTOSE PHOSPHATE SHUNT. Pentose phosphate shunt is an anabolic pathway that occurs in the cytoplasm Generates 3 ,4, 5, 6 and 7 carbon sugars and NADPH Functions:
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Pentose phosphate shunt is an anabolic pathway that occurs in the cytoplasm • Generates 3 ,4, 5, 6 and 7 carbon sugars and NADPH • Functions: • a. To generate NADPH (the main hydrogen donor), for reductive biosynthesis reactions (fatty acid and steroids) in the cytoplasm. Enzymes involved in this pathway is found mainly in adipose tissue, liver, mammary glands and adrenal cortex • b. To provide the cell with ribose-5-phosphate (R5P) for the synthesis of the nucleotides and nucleic acids (DNA and RNA), some coenzymes and ATP. • c. To form intermediates for glycolysis and gluconeogenesis • 4. Has both an oxidative and non-oxidative pathway
Oxidation steps utilises glucose 6-P and occurs at the start of the pathway and generates NADPH • 1 mole of NADPH each for every mole of glucose-6-phosphate (G6P) that enters the PPP web.indstate.edu/thcme/mwking/pentose-phospha...
Non oxidative reactions function to generate ribose 5-P • PPP also convert dietary 5-C sugars into 6 (fructose-6-phosphate) and 3 (glyceraldehyde-3-phosphate) carbon sugars which can be utilised by the glycolytic pathway. • Transketolase: transfer 2-C grps; require thiamine pyrophosphate as coenzyme • Transaldolase: transfer 3-carbon grps • Summary: • a. R5P production • b. 3 moles of 5-C sugar are converted, via the enzymes of the PPS, back into 2 moles of 6-C sugars and 1 mole of 3-C sugar • c. 6-C sugars can be recycled into the pathway in the form of G6P generating more NADPH • d. 3-C sugar generated is glyceraldehyde-3- phsphate and passed to glycolysis and oxidized to pyruvate • e. Pyruvate can be utilized by the gluconeogenic enzymes to generate more 6 carbon sugars (fructose-6-phosphate or glucose-6- phosphate). web.indstate.edu/thcme/mwking/pentose-phospha...
Regulation of Pentose Phosphate Shunt Metabolism of glucose 6-phosphate depends on cellular requirements • Cellular requirement for ribose 5-phosphate exceeds requirement for NADPH • a. glucose 6-P will not be oxidised via the oxidative phase of the PPS because this will generate NADPH as well. • b. Glucose 6-P will be oxidised via glycolysis to form fructose 6-P and glyceraldehyde 3-P which will combine to form ribose 5-P via the non oxidative phase
Cellular requirement for ribose 5-phosphate exceeds requirement for NADPH 5 Glu 6-P 5 Fruc. 6-P 1 Fruc. 1,6-bP DHAP Gly 3-P 2 Xyl 5-P 2 Erit-4-P 2 Sed 7-P 2 Gly 3-P 2 Xyl 5-P 4 Ribulose 5-P 2 Ribose 5-P 4 Ribose 5-P
Cellular requirement for ribose 5-phosphate exceeds requirement for NADPH Cellular requirement for ribose 5-phosphate equals that of NADPH 5 Glu 6-P Ribose 5-P + 2 NADPH
Cellular requirement for NADPH exceeds requirement for ribose 5-phosphate 6 NADPH 6 NADPH 6 x 6-fosphogluconate 6 x Glu 6-P 6 x Ribulose 5-P 6 CO2 2 Xyl 5-P 2 Ribose 5-P Pentose Phosphate Shunt (Non Oxidative) 2 Gly 3-P 2 Sed 7-P 2 Xyl 5-P 2 Fruc. 6-P 2 Erit-4-P Gluconeogenesis 4 x Glu 6-P 2 Fruc. 6-P 2 Gly 3-P Glu 6-P
3 NADPH 3 NADPH 3 x Glu 6-P 3 x 6-fosphogluconate 3 x Ribulose 5-P 3 CO2 Ribose 5-P Xyl 5-P Cellular requirement for NADPH exceeds requirement for ribose 5-phosphate but requires ATP Gly 3-P Sed 7-P Xyl 5-P Fruc. 6-P Erit-4-P 2 ADP (-2 ATP) 2 Fruc. 1,6-bP Fruc. 6-P Gly 3-P 5 NADH 2 Gly 3-P (4) 2 DHAP Glycolysis 5 Pyruvate + 10 ATP