CHAPTER 5. PENTOSE PHOSPHATE PATHWAY docx

1 CHAPTER 5. PENTOSE PHOSPHATE PATHWAY INTERNATIONAL UNIVERSITY SCHOOL OF BIOTECHNOLOGY BIOCHEMISTRY 2 Learning objectives To know the enzyme joining the PPP To understand the pathways to form the ribose 5-phosphate To understand the regulation of PPP 3 Content  Functions of the pentose phosphate pathway  Oxidative reactions leading from glucose 6-phosphate to ribose 5-phosphate  Non-oxidative reactions leading to the formation of intermediates of glycolysis 4 glucose glucose pentose 6-phosphate phosphate pathway glycogen glycolysis 5 FUNCTIONS OF THE PENTOSE PHOSPHATE PATHWAY  Provide reduced NADP for synthetic reactions, e.g. fatty acid synthesis and reduction of glutathione  Provide pentose phosphate for nucleic acid synthesis 6 7 Phosphopentose pathway Produces NADPH and ribose-5-phosphate NADH and NADPH although chemically similar they are not metabolically exchangeable. Ratios of [NAD+]/[NADH] ~ 1000 favors metabolite oxidation, whereas ratios of [NADP+]/[NADPH] ~ 0.01 favors reductive biosynthesis. Many anabolic pathways require the reducing power of NADPH for synthesis including Fatty acid synthesis and the synthesis of cholesterol. 3G-6-P + 6NADP + + 3H 2 O 6NADPH + 6H+ 3CO 2 + 2F6P + GAP 8 9 The pathway consists of three parts 1. Oxidative reactions: 3G-6-P + 6NADP + + 3H 2 O 6NADPH + 3CO 2 + 3Ribulose-5-PO 4 2. Isomerization and epimerization reactions: 3Ribulose-5-PO 4 Ribose -5-PO 4 + 2Xylulose-5-PO 4 3. A series of C-C bond cleavage and formations: Ribose-5-PO 4 + 2Xyluose-5-PO 4 2F-6-P + GAP 10 [...]... skeletons in the Phosphopentose pathway 16 The pentose pathway control 17 The need for NADPH is controlled by glucose dehydrogenase, however, when ribose -5 -phosphate is needed (DNA and RNA synthesis) it can be made from the reverse of the transaldolase and transketolase reactions from Fructose-6-PO4 and GAP One fate of G6P is the pentose pathway 18 The pentose pathway is a shunt  The pathway begins with... products of the pentose pathway are glyceraldehyde 3-P and fructose 6-P; two intermediates further down in the glycolytic pathway  It is for this reason that the pentose pathway is often referred to as a shunt 19 It’s a shunt 20 What does the pentose phosphate pathway achieve?  The pathway yields reducing potential in the form of NADPH to be used in anabolic reactions requiring electrons  The pathway yields... Transketolase requires the coenzyme thiamine pyrophosphate (TPP), the transaldolase does not 33  Transketolase (TPP) and transaldolase are the link back to glycolysis  Glyceraldehyde 3 -phosphate  Fructose 6 -phosphate  Net result: 34 3C5  2C6 + C3 Remember which reactions require TPP 35 Ingested ribose can enter the glycolytic pathway through the pentose pathway 36 ... glucose 6phosphate DH (G6PD) reaction is the rate limiting step and is essentially irreversible There is a medical story for this enzyme 26 Cells have a greater need for NADPH than ribose 5 -phosphate Regulatory enzyme 5 carbon atoms 27 28 Regulatory enzyme The enzyme is highly specific for NADP+; the Km for NAD+ is 1000 greater than for NADP+ 29 30 31 32 The nonoxidative phase of the pentose pathway. ..Glucose-6 phosphate dehydrogenase 11 Phosphogluconate dehydrogenase 12 Ribulose-5-PO4 isomerase 13 Two enzymes control the rearrangement of carbon skeletons which result in the production of Glyceraldehyde-3 -phosphate and Fructose- 6phosphate Transketolase transfers C2 units: TPP requiring enzyme like pyruvate dehydrogenase... electrons  The pathway yields ribose 5phosphate – Nucleotide biosynthesis leading to:   21  DNA RNA Various cofactors (CoA, FAD, SAM, NAD+/NADP+) 22 23 NADPH is a phosphorylated form of NADH In general, with some exceptions, NADH is used to drive the phosphorylation of ADP to ATP NADPH is used where reducing potential is required for synthetic reactions 24 The pentose pathway can be divided into two . the ribose 5- phosphate To understand the regulation of PPP 3 Content  Functions of the pentose phosphate pathway  Oxidative reactions leading from glucose 6 -phosphate to ribose 5- phosphate  Non-oxidative. intermediates of glycolysis 4 glucose glucose pentose 6 -phosphate phosphate pathway glycogen glycolysis 5 FUNCTIONS OF THE PENTOSE PHOSPHATE PATHWAY  Provide reduced NADP for synthetic. 1 CHAPTER 5. PENTOSE PHOSPHATE PATHWAY INTERNATIONAL UNIVERSITY SCHOOL OF BIOTECHNOLOGY BIOCHEMISTRY 2 Learning objectives To know the enzyme joining the PPP To understand the pathways