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Premium member Presentation Transcript GLYCOLYSIS: GLYCOLYSIS DIFFERENT PHASES FATE OF PYRUVATE NET ATP GAIN REGULATION BY VIRAL VYASGlycolysis : Glycolysis Glycolysis ( Greek glykys – sweet; lysis – splitting) involves the breakdown of glucose molecules through a series of reactions catalyzed by a set of enzymes such that a 6 – C sugar forms a 3 – C compound. Glycolysis isn’t set reaction that take place in the cytoplasm of prokaryotes & euckaryotes . ROLE OF GLYCOLYSIS:- TO PRODUCE ENERGY(BOTH DIRECTLY & BY SUPPLYING) SUBSTRATE FOR THE CITRIC ACID & OXIDATIVE PHOSPHORYLATION & TO PRODUSE INTERMEDIATES FOR BIOSYNTHETIC PATHWAYS. Significance of Glucose in biological systems A major fuel source of the body hence occupies a central position in metabolism Most of the tissues require some amt. of glucose for their proper functions; however in brain the requirement is significant and erythrocytes which lack mitochondria rely on glucose as their metabolic fuel carrying out anaerobic glycolysis . In higher forms of life, glucose has three different fates.Major pathway of glucose utilization in higher forms: Major pathway of glucose utilization in higher forms Glycogen (or starch, sucrose) GLUCOSE Ribose sugar Pyruvate, lactate Fate of glucose in the body – may be stored in a complex form as glycogen; oxidized to pyruvate by glycolysis or oxidized to pentose by Pentose phosphate pathwaySignificance of Glycolysis: Significance of Glycolysis It is the principal route for glucose metabolism and the metabolism of other hexoses (fructose, galactose ) Its ability to function under anaerobic condition is of significance, as it allows skeletal muscle to function and survive under anoxic episodes by providing ATP (glycogen-glucose- pyruvate -ATP). In pathological conditions like fast growing cancer cells glycolysis proceeds at a higher rate than the requirement of TCA cycle, due which the large amts. of pyruvate formed gets converted to lactate producing a local acidic environment in the tumors.Glycolysis under anaerobic condition: Glycolysis under anaerobic condition Involves anaerobic degradation of glucose and is also termed as Fermentation in general During muscle contraction in anaerobic medium , lactate appears as the end product Anaerobic glycolysis however has a price, for it limits the amount of ATP generated per molecule of glucose, due which much more glucose is metabolized in anaerobic medium During anaerobic condition, mitochondrial re oxidation of NADH (formed during glycolysis) is impaired , which is then reoxidized to NAD by reducing pyruvate to lactate. When oxygen is supplied, the lactate then disappears . However, in aerobic condition, pyruvate forms the end product being further oxidised to CO 2 and waterPowerPoint Presentation: Step 1 : ( phosphorylation ) glucose is phosphorylared by ATP to form a sugar phosphate. The negative charge of phosphate passage of the sugar phosphate through the plasma membrane,trapping glucose inside the cell.. This irreversible reaction is catalyzed by hexokinase called glucokinase ( hexokinase D). Hexokinase &PowerPoint Presentation: Also other kinases,requires divalent metal ion as Mg2+ or Mn2+ for activity. Hexocinase & glucokinase are isoenzymes .PowerPoint Presentation: STEP 2 : (ISOMERIZATION) A reversible rearrangement of the chemical structure ( isomerization ) of glucose 6-phosphate to fructose 6-phosphate is a conversion of an aldose in to a ketose . Step 3 : ( PHOSPHORYLATION) The new hydroxyl group on carbon 1 is phosphorylated by ATP to fructose 1,6-bisphosphate. The prefix bis that meansPowerPoint Presentation: That two phosphate groups are present, & connected by an anhydried bond.this irreversible is catalyzed by an alloteric enzyme PHOSPHOFRUCTOKINASE…. STEP 4 : (CLEAVAGE) The six carbon sugar is cleaved to produce two three- carbon molecules- glyceraldehyde 3-phosphate (GAP) & dihydroxyacetone phosphate (DHAP) can proceed immediately through glycolysis .PowerPoint Presentation: STEP 5 : (ISOMERIZATION) Dihydroxyacetone phosphate is isomerized to formglyceraldehyde 3-phosphate. The isomerization of these three-carbon phosphorylated sugar is catalyzed by triose phosphate isomerase .PowerPoint Presentation: STEP 6 : The two molecules of glyceraldehyde 3-phosphate are oxidized. Enzyme glyceraldehyde 3-phosphate dehydrogenase catalyzes the conversion of glyceraldehyde 3-phosphate in to 1,3-bisphosphosphoglycerate (1,3 BGP). The reaction occurs in two steps : first the oxidation of the aldehyde to a carboxylic acid by NAD+ & second the joining of carboxylicPowerPoint Presentation: Acid & orthophosphate to form the acyl -phosphate product. INDOACETATE(Toxic comp) is a potent inhibitor of the glyceraldehyde-3 phosphate dehydrogenase because it forms a covalent derivative of the essentional –SH(THIOESTER GROUP) group of the enzyme of the active site, rendering it inactive.PowerPoint Presentation: STEP 7 : The transfer of the high-energy phosphate group that was generated in step 6 to ADP from ATP. The formation of ATP is required to as substrate-level phophorylation because the phosphate donor 1,3-BPG , is a substrate with high phosphoryl -transfer potential. STEP 8 : The remaining phosphate ester linkage in 3-phosphoglycerate, whichPowerPoint Presentation: Has a relative low free energy of hydrolysis, is moved from carbon 3 to carbon 2 form 2-phospoglycerate. STEP 9 : The removal of water form 2-phosphoglycerare creates a high-energy enol phosphate linkage . Enzyme catalyzing this step , enolase is inhibiting by FLUORIDE.(toxic compound or inhibator )PowerPoint Presentation: STEP 10 : The transfer of the high-energy phosphate group that was generated in steap 9 to ADP forms ATP. This last step in glycolysis is the irreversible transfer of the phosphoryl group from phosphoenolpyruvate to ADP is catalyzed by pyruvate kinase . Pyruvate kinase requires either k+ or mg2+.Fate of Pyruvate: Fate of Pyruvate Glucose glycolysis Anaerobic cond n 2 Pyruvate Anaerobic cond n 2CO 2 aerobic cond n 2 Ethanol + 2 CO 2 2 Lactate (in yeast) 2 Acetyl CoA (in contracting muscle, RBCs) citric acid cycle 4 CO 2 + 4 H 2 O (animal, plant, and mo s under aerobic conditions)PowerPoint Presentation: Under aerobic conditions, pyruvate can be converated by pyruvate dehydrogenase to acetyl CoAenzyme.which can enter the cirric acid cycle.under anarobic condition,pyruvate is convarted to latctate by latcate dehydrognase (LDH).the NAD+ regenerated by this reaction allows glycolysis to continue ,despite the lake of oxygen .When oxygen becomes available,PowerPoint Presentation: The lactate is converted back to pyruvate .in anarobic conditions,yeast & other organisms carry out alcholic fermentation that converts pyruvate to acetaldhyde & then ethenol,regenerating NAD+ that allows glycolysis to continue.NET ATP : -: NET ATP : - 2 ATP expended 4 ATP produced (2 from each of two 3C fragments from glucose) Net production of 2 ~P bonds of ATP per glucose . Glycolysis Pathway (omitting H + ): glucose + 2 NAD + + 2 ADP + 2 P i = 2 pyruvate + 2 NADH + 2 ATPGlycolysis Summary: Glycolysis Summary Copyright Cmassengale Takes place in the Cytoplasm Anaerobic (Doesn’t Use Oxygen) Requires input of 2 ATP Glucose split into two molecules of Pyruvate or Pyruvic AcidGlycolysis Summary: Glycolysis Summary Also produces 2 NADH and 4 ATP Pyruvate is oxidized to Acetyl CoA and CO 2 is removed Copyright CmassengaleREGULATION: REGULATIONREGULATION PROCESS : -: REGULATION PROCESS : - The rate at which the glycolytic pathway operates is controlled primarily by allosteric regulation of three enzymes : hexokinase , PFK-1 , and pyruvate kinase . The reaction catalyzed by these enzymes are irreversible. A high AMP concentration activates PFK-1 and pyruvate kinase . In contrast ,a high ATPPowerPoint Presentation: Concentration inhibits both enzymes…citrate & acetyl- CoA , which indicate that alternative energy sources are available ,inhibit PFK-1 & pyruvate kinase,respectivaly , other allosteric effectors include fructose-6-phosphate, which stimulates PFK-1 activity & glucose-6-phosphate,which inhibits the hexokinasePowerPoint Presentation: Finally ,fructose-2,6-bisphosphate stimulates glycolysis by activiting PFK-1 & fructose-2,6 bisphosphate stimulates glycolysis by activating PFK-1 & 1,6-bisphosphate activates pyruvate kinase ….PowerPoint Presentation: ENZYME ACTIVATOR INHIBITOR Hexokinase ----- GLU-6-P PFK-1 fru-2,6-bispho citrate,ATP fru-6-pho,AMP Pyruvate fru-1,6-bispho, acetyl- CoA , kinase AMP ATP… You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.