Unit 3: Carbon Oxidation

((Unit-3))((Canton oxidation)):- ((Part-1)) Gly rouge's Glycolysis (Greex, glycos sugars, lysis s an important universal control pathway not only diseulu tien is of glucose metabolism, in plants and animasy, but as ina great many mkyo- Onganlems. Glyenipais is a catabolic pathway in which, a six courbon Suyan knowna gurose is sprit inme (or break doun) of a thrice-cariton Sergan Called Rynovate. two molecuies - Simply Glycolysts is the metaboite (catecburic) prath waly that converts glucose into Pyruvic acids with release of energy. This multistep process yields too ATP maerules containing Free energy, towo pyruvate moleures, electron carrying molecutes of water- NAD Hang of NADH, and energy two those cules Alycolysis can orture with of oxygen glycory's In the abscente on without oxygen. on the presence is the First stage of cellular respiration. of oxygen glycolysis allows cals to make small amounts of ATP through a proces of Fermentation. Glycolysis takes place in the cytosol of cells cytoplasm. the There are 10 down sugar, so there are lo steps organik af by the onder in upon the system. enzymes invoved in Steps breaking of glycolysis are which specific enzymes act opda Orl Rks YT Channel Step-1- "In the 1st step of glycolysis the onxy urbexokinase Phosphorylatetes in add a cell cytoplasm. phosphate groop toto glucose on this proces, a phosphate group From FMP is tomas Ferred to gurose producing glucose 6-phosphate OR GEP proress. one molecule of ATP is consumely diving this step on this steps the enzyme phosphogluco mutase somerizes Gep into its isomes Fructose 6-phosphate, or FEP Isomers have the same moterviers fermula as each other but different attomic, arrangements. this step the enzyme phospho fructokinave eses anathes ATP molecule to transfer a ph phosphate group to FGP (Fructose, 6-phosphate) in order to from Fructose 1,6-bis phosphate 吐。 Step-y: The enxyme dildolase splits Splits Fructose 16 bis phosphate in to a ketone l'e dihydroxyacetone phosphate (DHAP) and an aldehyde 2e glyceraldehyde 3-phosphate (GAP) morecure, which are isomer of each other. Step-s: The enzyme triose -phosphate isomerase Converts DHAP INDIGAP. GAP is the substrate needed For the next step of glycolysis. Step-6- In these step, the enzyme glyceraldehyde 8- phosphate dehydrogenase (GAPDH) Serves two Functions in this reaction. First, it dehydrogenates GAP (Glyceraldehyde, 3- Phosphate) by trans Ferning one of its hydrogen (47) moterine to the mecotinamide adenine Udinucleotide (NAD) to form NADH +41. -In next, GAPDH adds a phosphate from the cytosol to the oxidized GAP to Form 1,3-bis phas phoge phoglycerate (BPG). Step 7: In this step, th enxy me phosphoglycerskinave transfers a phosphate from BPG to a maecule of ADP to form ATP. This happens to each moleme of BPG. This reaction yields twe 3-phosphoglyrer (3 PGA) molecules & tevo ATP molecule. ak Step-s: The enzyme phosphoglycers mutrase necorates the phosphate group (P) of the twoO 3 PGA molecules form the thined to the second Carbon to form two, 2-phospho glycerate (2 PGA) molecules Step-9- In this step, the enzyme enolase removes a molecule of water from 2-phosphoglycerate to form phospho enol pyruvate. (PEP). Ster on this final step, The enxyme pyruvate kinase transfers a phosphate from PEP to ADP to form pyruvate and ATP. This happens for each molecule of PEP. -This recetion Yields towo molecue of Pyruvate & two ATP morewies 34" Ranjan Kumare Sahoo YT channes" A Fate of Pyruvate The term "Pyruvate." is used when it is present in the aqueous fyauvic acid medium on cell sap in the living cells. Hove ever the term is used when il is prreseard in dring, solid state. Pyruvate is the end product of glycolysis in the cytosol of living rolls. The Fate of Pyruvate depends on two condition ie when the oxgen is present Capsobic condition) os not (anaerobic condition). (1) The Fate of Pyruvate, in case of aprobic rεξγί τη λίση In the presence of oxygen (aerobic condition) Pyruvate is converted to acetyl-CoA by the penzyme lyruvate dehydrogenase complex, which enter the TCA lycre where longe amount of energy is generated in the mitochondola.. dehydrigonese complex The pyruvate made of of three enzyme the Fi(plyruvate dehydrogenase) Ez (dihydrolipay) trans are telase) & E3 (qihychulipoy, achydrogenase Pyruvate me de hyshugonase requires 5 to enzymes For this treaction Namely, TPP, lipiate, COA SH, FAD, NADT Pyruvate NADT NADH Co-enzyme Acetyl-CoA+ Pyruvate Dehydrogenase Comprex The fate of pynu vate in anaesbic onli hoo en angerobic conditions pyruvate partitioned Fermentation and arccholic Fermentation. aud in to lactic a REL YT Chamel" (a) Pyruvate in lactic auid Fermentation when tissue conlts be supplied when less oxygen 3- by oxigen exc by oxigen enduring ePy from NADH exeacise Gura te act as a teaminal (firmed during glycolysis) and converted into lactate, a procens called lactic acid Ferimentation. Pyruvate + NADH lactate + NAD lactare Dehydrogense (5) Fak of Pyruvak in asetetic Seamentation: - Yeast and other micro-organisms Ferement glucase into ethanel.. Glycolytic end product enteres into alcoholic, Fermentation, this Step takes place via a two step Reaction, • The First step the decarboxylation of Pyruvate, whene Pyruvate changes into acetal dohyde by losing carbon by the action of Pyruvate, decarboxylate, enzyme In Presence of Trpå matt Pyruvate Acefardchyte (0) • In the 2nd step, acetal dehyde accepts an erectom From NADH (Framed during glycolysis) to restone it into NADT for the further cyre, and converted into ethanol by the action of alwhos dehydrogenase enzyme. Acetas dehyde +NADH Ethanol + NAit alcohol Dehydrogenase Reguration of Glycolysis Glycolysis is a multistep cactabolic Process inwoner mutiple enzyme for its comapletion. The Flux through the glycolytic pathway must be adjusted in response to conditions both inside and out side the cens. The conversion of glucose into ryruvate is per neguinted to meet cellulan needs like energy, ATP, and synthesis and other products like fatty acids. In metabolic reactions pathways, enzymes catclyzing ane inneversible softly Control in off in on gly traysis, the pokntintly sites of 4 reactions catalyzed by hexokinase, phosphe fruito kinase and Pyruvate kinase are vintuany irenevesible. alteme, these craymes cwould be expected to have regulatory as well as catalytic notes. In fact, een each of them control site. There Their activities ane Senver oy regulated by the neversible binding of allosteric effectors on modification by covatent Regulation of guycolysis by different enzymes is as follows: By phas pho Fructose kinase : phospho Fructo kinase (PSK) catalyses the early steps of glycolysis involving phos pho rytation of Fructose-6-phosphate to fructose -1,6-bisphosphate with ATP as the phosphate, denor. By Rey Y channel. phes phofructose kinase is the most important central element in the glycolytic pathiday, levels of ATP anostenically inhit the enzyme, this lowering its affinity For for fructose & Phosphate. A high correntsection of ATP Convents the hyperabolic binding crave of Fructose 6-phosphate into a sigmadidal one. ATP evicts this effed by bineling to a thout is distinct form the Catalytic site. Catalytic Specific regulatiry site Ampe rreverices the inhibitory action of ATP and so the activity of the enzyme ficreceses when the AIP/Amp ratio is lowered..." - In other words, glyrdysis is stimulated as the energy charge FAILS A FOIL in PH also inhibits phospho Fructo kinase activity. The inhibition of phosphofiwctokinase by H¹ prevents excest ive formation of lactic acid. - In 1980, Fructose 2,6-bis phosphate, was identified as a potent activator actiontes bis phosphate off phospho fructokinase. Fructose 3,6-bis phosphofructokinase by increasing its affinity For fauctose & phosphite and diminishing the inhibitory elfect of ATP phospho Fructose kinase is allo Sensitive to inhibition by almost all the products of glycolysis like phosphorenol Pyruvaje (PEP glycoly-pan), the phosphe glycone ackd 2-phosphoglycerle alig (3-PGA), 12-bisphosphatecglylenic acid (BPGA) apart from Air &POR - This enzyme is quo sensitive to inhibition by the inhibition by Incoganic Incoganic phosphate (ip) and andys calcium ion (Ca). However Salt of Nat & kt. By Hexokinase Hexo kinase, the enzyme catalyzing the first step of glycolysis, is inhibited by the products, gilcose 6-phosphate. -High concentration of this mole (wie se sigme the cell nolongor nequities glucose for energy, for storage in the fare form of glycogen say a source of biosynthetic precursors and the glucose will be left in the cell For example when phosphofructo kinase is inactive, the concentration of Fructose 6-Prosphate rises. In turn, the leveret glucose 6-phosphate nises because it is in equilibrium with Fructose 6-phosphate. equilibrium Hence, the inhibition of phospho Fructo kinare leads to the inhibition ef hexokinase 3) By Pyruvate kinase & Pyruvate kinase, the enzyme, catalyzing the thing frane vertsible Step in glycolysis, control the out flow form this pathway. - This Fines Steps yield ATP and Pyruvate a central metabolic intermediate that con oxidized furthere or used as a buiding bete blocks. - Several isozymic forms of pyruvate kinase & encoded by different genes ane present in mammals the Litype & m type (aliver & musue &brain) The L&m Forms of Pyruvate kinase have many properties in common. - Both bind phospho encr pyruvic acid go-operatively. Fructose 1,6-bis Phosphate, the procluct of mereding inne versible step in activates both iso isoxyma on comming high Flux glycolysis, to en labie them to keep fare with the of inten mediates. "Riks YT channel" - ATP allo sterically inhibits both the la the im forms of Pyruvate kinue to si slow glycolysis when the energy charge is high. Finnuy, annine (Synthe sixed in one step from Pyruvate) also alvesterical inhibits pyruvate abundant. kinesies to signal that Plui loding Balso avesterically 4 phospho Fructo phosphotsrinsferase (PEP): This enxyme also has a role in Frequration of glycolys's Fructose whichcatalyses the phosphorylation of 6-phosphate As the phosphate doner. using inorganic phosphate (ipar) and not Aip - This reaction is freely reversible." and back ward reactions will depend The reactive rate of Forward on the concentrations of aivalent metale (mgat) berase these influence the remant of fire energy meie lased in the hydrolysis of ipp - The optimum activity of PEP is either equal to os catalytic potential of Phospho fructo kinase (PFK).. greater than the • Thus in the atore absente of PFK, PEP can catalyze the formation of Fructose 1, 6-bisphosphate.. Oxidatue Decarboxilation of Pyruvate -Oxidative decarboxitation of Pyruvate Prvolves the removal offe Carboxylate group from it as a more cule of carbon dioxide (Cog) by oxidation reaction It is an inne vesible process. along witts Acetyl CoA. Pyruvate dehydrogenase complex (PDC) is a complex of a enzyme that converts Pyruvate into aretyl co-A by the procen of oxidative decarbuхулант. The oxidative decarboxl lation of pyruvatre to form Aretyl-CoA & the link between Glycolysis and the cytric cycle. The reaction occurs in the mitochondrialmatrix. Pyruvate Dehydrogenase complex (PDC) PDC is a lange multiple enxyme composed of Pyruvate dehydrogenase os pyruvate decorboxylase (E) 2. Dihydroliroy! transacetylase (E₂) Dihydrolipayı dehydrogenase (E3) The enzyme complex auso consists of 5 coenzymes the Thiamine Pynophosphate (Trp), Lipoic acid (LA), lavin adenine dinucleotid (FAD), Coenzym A (COA) and Nicotinamide adenine dinucles file (NAD) Poy Rk vi channel. All these enzymes and coenzymes ane organized Rrito a cruster to keep the pecsthetic group Bo (cove together, thus allowing the reaction intermedicates to read quickly with each other. They three enzyme bond te Ecentyme Components associated by the non fovevent the Pyruvate dehydrogenase complex when they are mixed at theutics PH in absence of used.. mechanism of Diecanboxilation of Rypusive fyruvate into Acytyl-COA -There are 5 steps off for conversion of Pyruvate into Acetyl-cop which is catalyzed by PDC (Pyruvate dehydrogenase Complex. The enxyme (Poc) cannies out the five consecutive reactions in the decarboxylation & dehydrogenation of Ryruvate. Step1: In this step Pyruvate mencets with thiamine Pyro pst phosphate (Trp) of Pyruvate dehydrogenase Ei 1 endergoing decarboxylation to form he hydroxye thely derivative of thiazol ring of TPP of F Pyruvate + E- TPP mg1 • E1 Hydroxyethyl TPP + Cog Step2 Pyruverte dehydrogenase troan sfers two electrons and the aretyl group from TPP to oxidized Form of lipoyllysyl group of the cone enxyme, dip dihyctrulipory! transacetylase (Es) to form arétyl thloester of the reduced lipoyl group. E- Hydro Xy ethey! TIP + F₂- Lipoic acid Ex-TPP + E Acetyl lipoic acid Step-38- In this meactive step, the acetyle group of the are tyl ripor Hapo lipoic acid enzyme complex is tranferred to a molecule of Co-enzyme-A (COA SH) to form the Fully reducet (allsuighid or dithion) Form of lipoic acid enzyme complex. Ex-Acetyl liphoic acid + COA-SH = Fo-Reduced lipophilic acid <+Acetyl-S-COR. Step-4: Herre, the third enzyme, dihydrolipay) dehydrogenase, E3 reacts with the fully realvved form of u poic acid enzyme (12) Complex and the hydrogen atom from the redured Hpoje "poy! group are transfering to the FAD prosthetic group of the thing enzyme, Es and by this FAD is reduced to FADHZ. Ez-Reduced lipoic acid + E3 FAD Ez-Oxidized lipoicauld + E3-FADH2 Step-58-9n this final reaction, the nedured FAD group of dihydoulipoy 2 dehytrage naso (E3) is neoxidized by transferring hydrogen atom 10 NADT and there by NADH IS Produced This reaction is catalyzed by the thing enxyme E3- E-FADH NAD E2-FAD+ NADIA TH Regulation of PDK (Gruvat Dehydrogense Complex):- Po fyruvate dehydrogenase complex (poc) which catalyzes the oxidative de carboxylakon et lyruvate is Regulated in 3 ways: End Procwy inhibition "Riks YT channel" Pyruvate dehyrugeranis inhibited by end product. Acetyl CoA & NADH, bath end products of the pyruvate dehydrogenase reaction, are potent anestesic Jehibitors of the enzyme. The inhibitory effects are reverse on the addition of coenzy A CANADT. 2) Feedback Regulation: The activity of poc is controlled by the energy charge PDC Components is Specifically inhibited by ATPOS GTP and activated by Amp. 3) covevent motification:- unfere condition of high concentrations of ATP, acetyl-CoA, and those of the intermediates of TCA Cylle, Further Frimation of acetyl-CoA is slowed down. This is accomplished by covalent modification PDH is regulated by phosphorylation & dephosphorylation. POIt is active ces a dephosphoenzyme while it is inactive as phospho enxyme. - PDH kinase (nesponsible to form inactive PDH) is promoted by AFE NAD H and acetyl CoA, while it is inhibited by NADT, COA and Pyruvate. PDH activity is prometed byaça?", ma't ion. NADH Shu Hie The midochouchsiat NADH shuties, ane Systems used to transport the redu reducing agents accross the inner mitochondrine membrane. The NADH produced in glycolysis can't cross the memlerne, but it can reduce another molecule that coun enors the membrane So that ils electrons can reach the erectoto transport chain. There ane tow two main NADH shuttle System suchas glycerol phosphate shuttle & (i) malate aspartate shuttle Glycerol phosphate shuttle present in the mitochondria of a Plant cells and in Some animal cell ahite malate-aspartate Shuttle miy present in Some animaes & near. not in plants. (a) Glycerol phosphate shutie (aps):- - The gifenol, 3-phosphate shuttle is a mechanisis that negenerates. NAD+ fram NADH, a a by product of glycdys's. reaction: gn-this shuttle the enzyme called cytoplasmic glyceros, 3-phosphate dehydrogenase I (CGPDIP) of the cytosos converts dihydroxyacetone phosphate Dilap sto glyceros 3-phuphate by oxidizing. NADU to NAD one molecule of NAPH/ NAD BY Rks Y Channel" Det Dihy chroxy acetone Phosphate Glycerol 3-phosphate (GSP dehydrogenase) Functim- the NADH Synthesixed in the toso glyrolysis to contribute to the oxidative phosphorylatim Pathway in the mitochondriους λο generate ATP. ely to sor ל Peath *b) malate-Aspartnje shuttle (MAS): The malate aspartate shuttle is a biochemical System for translocating Electrons produced during glycolysis accross the semi permeable innes membrane of the mitochondวางก Fos oxidative phosphorylation in eukaryotes. This electrons entere the electron transport chan of the milacendia via steduction equivalents to generate ATP. Mechanism? The primary enzymes in matat mauate shuttle is malate dehydrogenase. on 9t Prisent in two froms in the shuttle System ? e mitochondrina matate dehydrogenase & cytosoise dehydrogenase. - First These two enxyme are differentiated by their location Structure & theire catalyze their reaction in oposite direction in this process. cytosol: Ifrat in the cytosol, malate dehydrogenase Catalyses the reaction of oxaloacetate and NADA to preiduce maitate & NADI. In this process, two erechens generated NADH and an accompanying 114, ane attached the Oxaloacetate to form malate malate Oxalonie tak + NADH + H Dehydrogenase (eyctosur) malate + NADT mitocondria: Ence once malate is formed, the First antiporter (malate-alpha-ketoglutarate) imports the malate form cytosal into the mitochondrial matrix and also exports alpha-ketoglutarate from the matrix into the cytosol simultaneously. Aftern malate reaches ajears tate by NAD the mitichettriαι matrix it is convented to mitochonstrias malate dehydrogenase, during which is reduced with two electons to Form NADH. Oxaloare traite is then trans formed into asparatate by mito chondrial cupandate aminotransferase with supplied of glutamate. This aisu xieids Alpha-ketu glutarate. The Scand antipater (the glutamate cupestrite antiporter) imports grutermate From Fathe Cytos & into t te from the max Cytus8 itos8, into the matrix and exprits asparta matrix to the cytosol. once in the cytosol asporstate is convented to oxaloacetate by aspurtate aminotransferase. Le mitochondria Amilate debyhogenave malate + NAD →oxaloacetate + NAOH + H amina transformie Asparitate & Alpha- oxioarente + Glutamate An cytosul next Agantate keligloteret Agponterte aming oxaloacetate "RKS YT chanmee" transferase. Trừ carboxylic Acid (TCA) cycle on Cytic Arid cycle on kerebs cycle on the krebs The tricarboxψεις asid (TCA) Cycle on the citric acid cycle Gevels a series of chemical reaction used by all es aerobic organismu to reteve stret energy through the oxidation of are tye COA derived from Canbo hydrates, Fals & Proteins in te fatibabuytre courbon dioxide & Chemical energy in the form of ATP. On credditing the cycle provides precursors of certain amino acids, as athen blochemicalumering power pactions NADH that are used in numerou The TOA eycie ahene is pound of the lange glucose metabetism pathway by gruruse exidized and is oxili xil to form pyruvate, which's then enters the TCA Cylle os acetyl-CoA. The name of this metabolic pathway is derived from the citric aciq Ca type of tri carboxylic acid contrining of carboxylic group often called citrate) that is consumed and then regenatoate megenatorted by this sequence of reactions to complete the cycle. reduces NADT to NADH The eyeue consumes acetate and couter, waste" and produces carbon dioxide as a by-products. Site of ICA cyles In eukaryotic cell, the ytricacid cykle occurs In the matrix of the mitochondria. Prokaryotico to cene suchas yryle ocen in Cytesol 46 bacteria which lack mitochondrsia, the TCA The TCA Cycie occur in the protein nich matrix beti-con the crister ef mits Chenierten The cristae contain most of the enxymes that catalyze steps of of the electron trans port system and oxidative Off Phosphorylation, that follow the TCA Cщие. Discovery Several components and reactions of the TCA cycle were establich in the 1930s by the research of Albert Szent-Gyorgyl, whe received the Nobel Prize In physicsogy on medicine in 1937 Specially for his discovery opentalning to rumanic acid, a key component of the cycle. -The cytric acid eyere it self was Finally identified in 1937 by Hans Adolf kriebs and iv. A Johnson of the university s Sheffield, for which the firme received the Nobel Prize Por Physiology or medicine in 1953. Hence the ker kriebs cycle is named in honour of the Fuglish biochemist, sin Hans. A. kriebs. mechanism ousteps of Ten Cycle: TCA Cycle completes in the Following steps. Step1: In this Step Acetyl CoA (a tus canban moteure) joins with oxroacetate to form cytrate in the presence of water 311 and enzyme citrate Synthase. By RKS YT channel Step-2 on rext step citrrite is onvert ted into isocitrak (an isormen of citonte) by Aconitase enzyme. Step-3: Is citreute is oxidized to cupha-ketoglutarate A Five carbon dioxide. this reaction. reaction. •one NADH molecule Se socitrate dehydrogenase This is a riate lin dehydrogenase is an Limiting Step, os in Catalyzes this iso litronte allasterically entailed enzyme. Ster-y- Alpha-ketoglutarate is oxidised to molecule. This bingst A Second Co-enzyme A, Form 4 Carbon Foruming Succiny | COA. molecule of NADIA is produced crangsiden. molecule of carbon dioxide. Second Step- Succinyl CoA is then convented to succinate (4 carbm molecule) and by by Suctingl one atp moleculeis porduced. It is catalyzed -CoA Synthetase enzyme. Step-6:- Succinate is converted into Furmarcate (4 conibm molecure) and a molewle of FADHy is Produced. This is catalyzed by enzyme, succinate dehydrogenase enzymes." Step 7-In this step fumarate is converted into malate exatoaretrode is pructured (another 4 carbon molecule). This reaction is catalyzes by enzyme Fumarate with presence of water. Ster-8:9n this last step, the malate is then Convested into oxaloare tate the thing moleme of NADA is covo produced. Now oxalodeetate joins with aretyl co-A to form citrate an oft and thres generate anather seyet of TCA Cycle &.