BIOL 541 1st Edition Lecture 17Outline of Last Lecture I. ETC Outline of Current Lecture II.Pentose Phosphate PathwayIII. RegulationIV. Glycogen breakdownCurrent LectureBiochem Lecture 17- Pentose Phosphate Pathway:Phosphogluconate pathway or hexose mono phosphate shunt:PPP is a network of reactions. There are three possible scenarios. Two of which are in biosynthesis of lipids as production of NADPH, which is important as lots of H are required. Detoxifying free radicals are done by glutathione (co enzyme) and handles free radicals as glutathione with central CYS and converts peroxides to alcohol. Glutathione forms disulphide bonds, GLU SSG. NADPH reduces GLU SSG to glutathione.Production of NADPH in 1st couple of steps:Oxidation of Glucose 6 phosphate, alpha OH oxidized to aldehyde and NADP becomes the acceptor of electrons. Glucose 6 phosphate dehydrogenase is the regulated step. Lactonase gives aldehyde which is oxidized to acid. Acid is removed by deacetylation and sugar has 1 less C (ribolose). Sugar is isomerized to form ribose. This is the major source of ribose and deoxyribose for nucleotide. Ribose nucleotide is converted to deoxyribose for DNA. Lots of H are made through NADPH and ribose is used for growth as RNA and DNA.If lots of reducing power is needed, accumulation of ribose is avoided by series of reactions. Rearrangement of C back into 6 C sugar for recycling. Complex web as C-C bonds are strong. C=O helps by being shifted around for substitution and deletion for the manipulation of compounds.These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Glucose 6 phosphate = 36 C and ends up as 6 ribolose phosphate with 5 C only 30 C as 6 CO2 are lost. 6x5 C sugars are rearranged to produce 5x6 C sugar as 6C are fed back into the cycle. 2x 5C shift C=O to end to form aldehyde which is done by ribose isomerase. Ribolose 5 phosphate is flipped over to form 5 phospho xylose. 2,5 phospho ribolose to 2,5 riboses = 10= 3+7 and done by transketolase. 3 glyceraldehyde form and 4 phospho sedoheptulose, shift C=O and add 3+7 C and reposition as 6+4. Fructose 6 phosphate (6 C) isomerized into glucose 6 phosphate. Erythrose combined with xylolose= 5+4=9 C or 6C is fructose 6 phosphate and 3C is glyceraldehyde. This reaction is in equilibrium with DHAP to Fructose 1,6 phosphate and fructose 6 phosphate.2+2+1= 5 Fructose 6 phosphate.Phospho gluco isomerase flips isomer over to form 5 fructose 6 phosphate.Therefore, 6x5 C rearranged to make 5x6 C sugars. There is no wastage as H are made. NADPH for ribose as source and sink for metabolites. Erythrose is important for aromatic amino acids. Glycolysis products are also formed: 3 phospho glyceraldehyde.6 Glucose 6 phosphate + 12 NADP + 12 H2O -- 5 glucose 6 phospahate + 6 CO2 + 12 (NADPH+H) + Pi. Regulation:Glucose 6 phosphate is allosterically stimulated by NADP and inhibited by NADPH as this is the product. Competitive inhibition by 3 phospho glycerate is done by phosphor mutase. In presence of ROS (reactive oxygen species), activation of deactylation where removal of COOH is activated by mutase. 3 phospho glycerate is converted and removes the inhibition and NADPH detoxifies ROS.Cell stress in ROS also activates ATM (kinase) which activates another kinase which phosphorylates hsp (histone heat shock protein).ATM ----P38---hsp 27 (chaperones) ---- glucose 6 phosphate dehydrogenaseChaperones enable proper conformation by binding allosterically and activate glucose 6 phosphate dehydrogenase. Stress produces H in these pathways. TYR is phosphorylated by growth factors by increasing activity. Growth factors need a lots of ribose for mitosis and DNA synthesis. Gene can be induced. Insulin induces fat tissue as insulin is a anabolic for fatty acid synthesis. NADPH are needed in lots of numbers. Prolactin in mammary glands makes fat secreted in the milk. 2nd oxidation enzyme 6phosphate glucose dehydrogenase is also regulated as growth factors induce acetylation and activation and binding affinity for NADP. Deacetylated by different deacetylase SIRT (sensitive to energy status). Deacetylated by histone deacetylase C4 (HDAC4). Growth independent of energy status of cell.Glucose 6 phospho dehydrogenase can be mutated. Glucose isozyme in blood and ribosomes in the cell can not generate free radicals and hemolytic anemia develops. Drugs can induce free radicals and rupture RBC.Glycogen:Gycogen is a polymer of glucose and is identical to starch and called as animal starch. Alpha 1, 4 linkages and alpha 1,6 linkages as branches: spliced into another chain alpha 1,6 linkage. Difference between starch and glycogen is that glycogen branching is close together 1 and 4 residues whereas starch is 1 and 20 residues. Glycogen is needed for homeostasis where factors are kept constant in body of animals. Osmolarity of body fluids is 300 milli osmolarity and depends solely on the number of molecules and notsize. Thereby, 5000 molecules of glucose are stored and osmolarity is dealt with. Polymerisation enables osmolarity of 1 molecule. Synthesis of glucose by activating glucose. O- linked acetylation couple glucoseto nucleotide. Synthesis with sugar residue:Glucose 1 phosphate + Uridine TP ---- UDP- glucose + PPi -- pyrophosphatase- 2 pi. Reaction moves ---- in this direction.UDP- glucose pyrophorylase ---- 2 PP coupled together.Alpha and gamma phosphate groups are cleaved. Energy between alpha and beta are coupled to glucosefor UDP- glucose. Reaction is at equilibrium and as UDP- glucose is only required, reactants are added or the product is taken away so that only forward direction of the reaction occurs.Substrate for coupling needs a primer called glycogenin (protein) which exists as dimmer and at center ofglycogen molecule are alpha helices and beta strand. Enzyme takes UDP- glucose and attaches to OH of TYR (other than SER, THR). Protein has single TYR for attaching glucose. This continues until 10 to 20 glucose units are attached. Then glycogen synthase takes over where glycogen particle is created with 12layers and 40 nm across.Reaction is relatively simple: UDP –glucose + (Glc)n --- UDP +(Gln) n+1It can only add glucose in a linear direction. In order to get branches, a different enzyme called branchingenzyme called amylo – (1,4 -- 1,6) – transglycosylase which transfers glucose from glycogen in 1,4