Download as PPT, PDF, TXT or read online from Scribd
Download as ppt, pdf, or txt
You are on page 1/ 44
INTERNATIONAL UNIVERSITY
SCHOOL OF BIOTECHNOLOGY
CHAPTER 5. PENTOSE PHOSPHATE
PATHWAY
BIOCHEMISTRY
1 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
2 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 3 intermediates of glycolysis glycogen
glucose glucose pentose
6-phosphate phosphate pathway
4 glycolysis 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
5 6 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+ + 3H2O 6NADPH + 6H+ 3CO 2 + 2F6P + GAP
7 8 The pathway consists of three parts 1. Oxidative reactions: 2. 3G-6-P+6NADP+ + 3H2O6 NADPH+3CO2 + 3Ribulose-5-PO4
13 Two enzymes control the rearrangement of carbon skeletons which result in the production of Glyceraldehyde-3-phosphate and Fructose-6- phosphate. Transketolase transfers C2 units: TPP requiring enzyme like pyruvate dehydrogenase Transaldolase transfers C3 units: uses a shiffs base with an active lysine group 14 Transketolase requires TPP
15 The transition of carbon skeletons in the Phosphopentose pathway
16 The pentose pathway control
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 17 Fructose-6-PO and GAP 4 One fate of G6P is the pentose pathway.
18 The pentose pathway is a shunt.
The pathway begins with the glycolytic
intermediate glucose 6-P. It reconnects with glycolysis because two of the end 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 ribose 5-phosphate. – Nucleotide biosynthesis leading to: DNA RNA Various cofactors (CoA, FAD, SAM, NAD+/NADP+).
21 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 phases.
Non-oxidative interconversion of sugars
25 NADPH + H+ is formed from two separate reactions.
The glucose 6- phosphate DH (G6PD) reaction is the rate limiting step and is essentially irreversible.
There is a medical story
for this enzyme.
Cells have a greater
need for NADPH than 26 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
This entails extensive carbon atom
rearrangement.
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: 3C5 2C6 + C3
34 Remember which reactions require TPP
35 Ingested ribose can enter the glycolytic pathway through the pentose pathway.
36 37 Regulation of the Pentose Pathway
Glucose 6-phosphate DH is the regulatory
enzyme. NADPH is a potent competitive inhibitor of the enzyme. Usually the ratio NADPH/NADP+ is high so the enzyme is inhibited. But, with increased demand for NADPH, the ratio decreases and enzyme activity is stimulated. 38 The reactions of the non-oxidative portion of the pentose pathway are readily reversible.
The concentrations of the products and
reactants can shift depending on the metabolic needs of a particular cell or tissue.
39 Rapidly dividing cells require more ribose 5- phosphate than NADPH.
40 The need for NADPH and ribose 5-phosphate is balanced.
41 More NADPH is needed than ribose 5-phosphate; Fatty acid synthesis in adipose cells.
