Pentose phosphate pathway

Pentose phosphate pathway

1. PENTOSE PHOSPHATE PATHWAY NILOUFER M.A and Dr. KAYEEN VADAKKAN DEPARTMENT OF BIOTECHNOLOGY ST.MARY’S COLLEGE, THRISSUR

2. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR INTRODUCTION Also known as Hexose Monophosphate (HMP)shunt. Alternative route for the metabolism of glucose. More complex pathway than glycolysis . It helps in- Formation of NADPH for synthesis of fatty acids ,steroids. Maintaining reduced glutathione for antioxidant activity. Synthesis of ribose for nucleotide and nucleic acid formation.

3. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR PENTOSE PHOSPHATE PATHWAY Like glycolysis it occurs in c ytosol . Oxidation is achieved by dehydrogenation using NADP + , not NAD + Its carried out in 2 step; >Irreversible oxidative phase: 3 molecules of glucose-6-phosphate give rise to 3 molecules of co 2 and 3 5-carbon sugars. >Reversible non-oxidative phase: Rearranged to regenerate 2 molecules of glucose-6-phosphate and 1 molecule of glyceraldehyde-3-phosphate.

4. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR OXIDATIVE PHASE In this phase, two molecules of   NADP +   are reduced to   NADPH , utilizing the energy from the conversion of   glucose-6-phosphate   into   ribulose - 5-phosphate . Dehydrogenation of glucose-6-phosphate to 6-phosphogluconolactone catalyzed by glucose-6-phosphate dehydrogenase . Followed by hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate by enzyme lactonase .

5. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR Decarboxylation follows with the conversion of 6-phosphogluconate into the ketopentose ribulose-5-phosphate. Overall equation is , Glucose 6-phosphate + 2 NADP +  + H 2 O → ribulose 5-phosphate + 2 NADPH + 2 H +  + CO 2 The net result is the production of NADPH , a reductant for biosynthetic reactions, and ribose-5-phosphate,a precursor for nucleotide synthesis.

6. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR NON-OXIDATIVE PHASE Ribulose-5-phosphate is the substrate for two enzymes; Ribose-5-phosphate ketoisomerase:ribulose-5-phosphate to the corresponding ribose-5-phosphate ,used for nucleotide and nucleic acid synthesis. Ribulose-5-phosphate 3-epimerase:alters the configuration about carbon giving xylulose-5-phosphate. Xylulose-5-phosphate (5c) and ribose-5-phosphate(5c) reacts to give glyceraldehydes-3-phosphate (3c) and sedoheptulose-7-phosphate(7c) by the enzyme Transketolase . Glyceraldehyde-3-phosphate (3c) and sedoheptulose-7-phosphate(7c) is acted by Transaldolase to give fructose-6-phosphate and erythrose-4-phosphate.

7. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR Erythrose-4-phosphate and xylulose-5-phosphate reacts in the presence of enzyme transketolase to give fructose-6-phosphate and glyceraldehyde-3-phosphate. Mg2+ and thiamin diphosphate (vitaminB1) as coenzyme Subsequently fructose-6-phosphate is isomerised to glucose-6-phosphate by enzyme phosphohexose isomerase . Net reaction: 3 ribulose-5-phosphate → 1 ribose-5-phosphate + 2 xylulose-5-phosphate → 2 fructose-6-phosphate + glyceraldehyde-3-phosphate A genetic defect in transketolase that lowers its affinity for TPP exacerbates the Wernicke-Korsakoff syndrome.

8. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR OXIDATIVE PHASE NON-OXIDATIVE PHASE

9. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR Entry of glucose-6-phosphate either into glycolysis or into the pentose phosphate pathway is largely determined by the relative concentration of NADP+ and NADPH. Regulation Glucose-6-phosphate dehydrogenase is the rate-controlling enzyme of this pathway. It is  allosterically  stimulated by NADP +  and strongly inhibited by NADPH. The ratio of NADPH:NADP +  is normally about 100:1 in liver cytosol . This makes the cytosol a highly-reducing environment. An NADPH-utilizing pathway forms NADP + , which stimulates Glucose-6-phosphate dehydrogenase to produce more NADPH. This step is also inhibited by acetyl CoA

10. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR Reactants Products Enzyme Description Glucose 6-phosphate + NADP+ →  6-phosphoglucono- δ- lactone  +  NADPH glucose 6-phosphate dehydrogenase Dehydrogenation . The hydroxyl on carbon 1 of glucose 6-phosphate turns into a carbonyl, generating a lactone , and, in the process,  NADPH  is generated. 6-phosphoglucono- δ- lactone  + H 2 O →  6-phosphogluconate  + H + 6-phosphogluconolactonase Hydrolysis 6-phosphogluconate  + NADP + →  ribulose 5-phosphate  +  NADPH  + CO 2 6-phosphogluconate dehydrogenase Oxidative  decarboxylation . NADP +  is the electron acceptor, generating another molecule of  NADPH , a CO 2 , and  ribulose 5-phosphate . : The entire set of reactions of oxidative phase can be summarized as follows:

11. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR The entire set of reactions of non-oxidative phase can be summarized as follows: Reactants Products Enzymes Ribulose-5-phosphate →  ribose 5-phosphate Ribose-5-phosphate isomerase Ribulose-5-phosphate →  xylulose-5-phosphate Ribulose-5-Phosphate 3-Epimerase Xylulose-5-phosphatate  +  ribose 5- phosphate →  glyceraldehyde - 3-phosphate  +  sedoheptulose - 7-phosphate Transketolase Sedoheptulose-7-phosphate  +  glyceraldehyde-3-phosphate →  erythrose-4-phosphate  +  fructose 6-phosphate Transaldolase Xylulose-5-phosphate +   erythrose - 4-phosphate →  glyceraldehyde - 3-phosphate +   fructose 6-phosphate Transketolase

12. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR

13. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR IMPORTANCE OF NADPH Bio-synthesis of fatty acid. Certain aminoacid involving the enzyme glutamate dehydrogenase . Antioxidant reaction-Glutathione mediated reaction of H2O2. Detoxification of drugs- cytochrome P450. Phagocytosis . Integrity of RBC membrane.

14. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR OUTCOME The primary results of the pathway are: The generation of reducing equivalents, in the form of NADPH, used in reductive biosynthesis reactions within cells (e.g. fatty acid synthesis). Production of ribose 5-phosphate(R5P), used in the synthesis of nucleotides and nucleic acids. Production of  erythrose 4-phosphate (E4P) used in the synthesis of aromatic amino acids.

15. PENTOSE PHOSPHATE PATHWAY, NILOUFER M.A, ST.MAR’YS COLLEGE - THRISSUR