Oxidation of Pyruvate and the Citric Acid Cycle

Circuit theory of finance and the role of incentivesin financial sector reformbyBiagio BossoneWorld BankNovember 1998SummaryThis paper analyzes the role of the financial system for economic growth and stability, andaddresses a number of core policy issues for financial sector reforms in emerging economies. Therole of finance is studied in the context of a circuit model with interacting rational, forward-looking, and heterogeneous agents. Finance is shown to essentially complement the price systemin coordinating decentralized intertemporal resource allocation choices from agents operatingunder limited information and incomplete trust. The paper also discusses the links betweenfinance and incentives to efficiency and stability in a circuit context. It assesses the implicationsfor financial sector reform policies and identifies incentives and incentive-compatible institutionsfor financial sector reform strategies in emerging economies.The author is intellectually indebted to the work of Prof. Augusto Graziani in the field ofmonetary circuit theory. The author wishes to thank Jerry Caprio, Stjin Claessens, and LarryPromisel for their helpful comments on earlier drafts of the paper. He bears full responsibility forany remaining errors and for the opinions expressed in the text. The author is especially gratefulto his wife Ornella for her invaluable support. For comments, contact Biagio Bossone, E-mail:Bbossone@worldbank.org, tel. (202) 473-3021, fax (202) 522-2031. 2TABLE OF CONTENTSINTRODUCTION 3I. FINANCE IN A MARKET ECONOMY . 4I.1 THE CIRCUIT PROCESS OF FINANCE . 4I.1.1 Assumptions and structure of the model 5I.1.2 Structural implications of CTF Oxidation of Pyruvate and the Citric Acid Cycle Oxidation of Pyruvate and the Citric Acid Cycle Bởi: OpenStaxCollege If oxygen is available, aerobic respiration will go forward In eukaryotic cells, the pyruvate molecules produced at the end of glycolysis are transported into mitochondria, which are the sites of cellular respiration There, pyruvate will be transformed into an acetyl group that will be picked up and activated by a carrier compound called coenzyme A (CoA) The resulting compound is called acetyl CoA CoA is made from vitamin B5, pantothenic acid Acetyl CoA can be used in a variety of ways by the cell, but its major function is to deliver the acetyl group derived from pyruvate to the next stage of the pathway in glucose catabolism Breakdown of Pyruvate In order for pyruvate, the product of glycolysis, to enter the next pathway, it must undergo several changes The conversion is a three-step process ([link]) Step A carboxyl group is removed from pyruvate, releasing a molecule of carbon dioxide into the surrounding medium The result of this step is a two-carbon hydroxyethyl group bound to the enzyme (pyruvate dehydrogenase) This is the first of the six carbons from the original glucose molecule to be removed This step proceeds twice (remember: there are two pyruvate molecules produced at the end of glycolsis) for every molecule of glucose metabolized; thus, two of the six carbons will have been removed at the end of both steps Step The hydroxyethyl group is oxidized to an acetyl group, and the electrons are picked up by NAD+, forming NADH The high-energy electrons from NADH will be used later to generate ATP Step The enzyme-bound acetyl group is transferred to CoA, producing a molecule of acetyl CoA 1/7 Oxidation of Pyruvate and the Citric Acid Cycle Upon entering the mitochondrial matrix, a multi-enzyme complex converts pyruvate into acetyl CoA In the process, carbon dioxide is released and one molecule of NADH is formed Note that during the second stage of glucose metabolism, whenever a carbon atom is removed, it is bound to two oxygen atoms, producing carbon dioxide, one of the major end products of cellular respiration Acetyl CoA to CO2 In the presence of oxygen, acetyl CoA delivers its acetyl group to a four-carbon molecule, oxaloacetate, to form citrate, a six-carbon molecule with three carboxyl groups; this pathway will harvest the remainder of the extractable energy from what began as a glucose molecule This single pathway is called by different names: the citric acid cycle (for the first intermediate formed—citric acid, or citrate—when acetate joins to the oxaloacetate), the TCA cycle (since citric acid or citrate and isocitrate are tricarboxylic acids), and the Krebs cycle, after Hans Krebs, who first identified the steps in the pathway in the 1930s in pigeon flight muscles Citric Acid Cycle Like the conversion of pyruvate to acetyl CoA, the citric acid cycle takes place in the matrix of mitochondria Almost all of the enzymes of the citric acid cycle are soluble, with the single exception of the enzyme succinate dehydrogenase, which is embedded in the inner membrane of the mitochondrion Unlike glycolysis, the citric acid cycle is a closed loop: The last part of the pathway regenerates the compound used in the first step The eight steps of the cycle are a series of redox, dehydration, hydration, and decarboxylation reactions that produce two carbon dioxide molecules, one GTP/ ATP, and reduced forms of NADH and FADH2 ([link]) This is considered an aerobic pathway because the NADH and FADH2 produced must transfer their electrons to the 2/7 Oxidation of Pyruvate and the Citric Acid Cycle next pathway in the system, which will use oxygen If this transfer does not occur, the oxidation steps of the citric acid cycle also not occur Note that the citric acid cycle produces very little ATP directly and does not directly consume oxygen In the citric acid cycle, the acetyl group from acetyl CoA is attached to a four-carbon oxaloacetate molecule to form a six-carbon citrate molecule Through a series of steps, citrate is oxidized, releasing two carbon dioxide molecules for each acetyl group fed into the cycle In the process, three NAD+ molecules are reduced to NADH, one FAD molecule is reduced to FADH2, and one ATP or GTP (depending on the cell type) is produced (by substrate-level phosphorylation) Because the final product of the citric acid cycle is also the first reactant, the cycle runs continuously in the presence of sufficient reactants (credit: modification of work by “Yikrazuul”/Wikimedia Commons) Steps in the Citric Acid Cycle Step Prior to the start of the first step, a transitional phase occurs during which pyruvic acid is converted to acetyl CoA Then, the first step of the cycle begins: This 3/7 Oxidation of Pyruvate and the Citric Acid Cycle is a condensation step, combining the two-carbon acetyl group with a four-carbon oxaloacetate molecule to form a six-carbon molecule of citrate CoA is ...Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants A case study of endosymbiotic gene transfer Claus Schnarrenberger 1 and William Martin 2 1 Institut fu È r Biologie, Freie Universita È t Berlin, Germany; 2 Institut fu È r Botanik III, Universita È tDu È sseldorf, Germany The citric acid or tricarboxylic acid cycle is a central element of higher-plant carbon metabolism which p rovides, among other things, electrons for oxidative phosphorylation i n t he inner mitochondrial membrane, intermediates for amin o- acid biosynthesis, and oxaloacetate for gluconeogenesis from succinate derived from fatty acids via the glyoxylate cycle in g lyoxysomes. The tricarboxylic acid cycle is a typical mitochondrial pathway and is widespread among a-pro- teobacteria, the group of eubacteria as de®ned under rRNA systematics f rom w hich mitochondria arose. Most of the enzymes of the tricarboxylic acid cycle are encoded in the nucleus in higher eukaryotes, and several have been previ- ously shown to branch with their homologues from a-pro- teobacteria, indicating that the eukaryotic nuclear genes were acquired from the mitochondrial genome during the course of evolution. Here, we investigate the individual evolutionary histories o f all of the enzymes of the tricar- boxylic acid c ycle and the glyoxylate cycle using p rotein maximum likelihood phylogenies, focusing on t he evo lu- tionary origin of the nuclear-encoded proteins in higher plants. The results indicate that about half of the proteins involved in this eukaryo tic pathway a re most similar t o their a-proteobacterial homologues, whereas the remainder are most similar to eubacterial, but not speci®cally a-proteo- bacterial, homologues. A consideration of (a) the process of lateral gene transfer among free-living prokaryotes and ( b) the mechanistics of endosymbiotic (symbiont-to-host) gene transfer reveals that it i s unrealistic t o expect a ll nuclear genes that were acquired from the a-proteobacterial ancestor of mitochondria to branch speci®cally with their homologues encoded in the genomes o f contemporary a-proteobacteria. Rather, even if molecular phylogenetics were to work perfectly ( which i t does not), then some nuclear-encoded proteins that were acquired from the a-proteobacterial ancestor of mitochondria should, in phylogenetic t rees, branch with homologues that are no longer found in most a-proteobacterial genomes, and some should reside on long branches that reveal anity to eubacterial rather than archaebacterial homologues, but no particular anity for any speci®c eubacterial donor. Keywords: glyoxysomes; microbodies; mitochondria; pathway evolution, pyruvate dehydrogenase. Metabolic pathways are units of biochemical function that encompass a number of su bstrate conversions leading from one chemical intermediate to another. The large amounts of accumulated sequence data from prokaryotic and eukary- otic sources provide novel opportunities to study the molecular evolution not only o f individual enzymes, b ut also of individual pathways consisting of several enzymatic substrate conversions. This opens the door to a number of new and intriguing questions in m olecular e volution, s uch a s the following. Were pathways assembled originally during the early phases of biochemical evolution, and subsequently been passed down through inheritance ever since? Do pathways evolve as coherent entities consisting o f the same group 1 CHAPTER 4: THE CITRIC ACID AND OXIDATIVE PHOSPHORYLATION INTERNATIONAL UNIVERSITY SCHOOL OF BIOTECHNOLOGY BIOCHEMISTRY 2 Learning objectives 1. To understand the intermediates in CAC 2. The ATPs produce in CAC 3. The CO2 is released in CAC 4. The electrons are transferred in the electron transport chain 5. The oxidative phosphorylation 3 Content Citric acid cycle Introduction Cellular location Catabolism Anabolism & catabolism Sources of acetyl-CoA Fatty acid –aminoacid- monosaccharides 4 Content Reactants & products Cyclical reaction pathway Fate of acetyl CoA carbon regulation: inhibition Energetics Anaerobic Anaplerotic reactions Oxidative phoshorylation Introduction Mitochondrial anatomy Shuttle system Introduction to the transport chain Comlex I- comlex II- comlex III and Cytochrome C- comlex IV 5 Citric Acid Cycle INTRODUCTION The citric acid cycle is a central metabolic pathway that completes the oxidative degradation of fatty acids, amino acids, and monosaccharides. During aerobic catabolism, these biomolecules are broken down to smaller molecules that ultimately contribute to a cell’s energetic or molecular needs. 6 FIG. 01: Citric acid cycle is the central metabolic pathway 7 INTRODUCTION Early metabolic steps, including glycolysis and the activity of the pyruvate dehydrogenase complex, yield a two-carbon fragment called an acetyl group, which is linked to a large cofactor known as coenzyme A (or CoA). It is during the citric acid cycle that acetyl-CoA is oxidized to the waste product, carbon dioxide, along with the reduction of the cofactors NAD+ and ubiquinone. 8 FIG. 02: Early catabolic pathway 9 FIG. 03: Citric acid cycle is the central metabolic pathway 10 INTRODUCTION The citric acid cycle serves two main purposes: 1.To increase the cell’s ATP-producing potential by generating a reduced electron carriers such as NADH and reduced ubiquinone; and 2.To provide the cell with a variety of metabolic precursors. [...]... carriers and their role in coupling the citric acid cycle to downstream reactions that produce ATP; Describe the amphibolic character of the citric acid cycle; and Understand the reactions that replenish citric acid cycle intermediates 13 CELLULAR LOCATION Both prokaryotic and eukaryotic cells use the citric acid cycle to help meet their energetic and molecular needs In respiring prokaryotes, the citric acid. ..FIG 04: Main purposes of CAC 11 INTRODUCTION Be able to describe the sources of acetyl groups that enter the citric acid cycle; Trace the conversion of substrates to products through each of the citric acid cycle’s eight reactions and understand how flux through the cycle is regulated; Understand the energetic output of the citric acid cycle; 12 INTRODUCTION Describe the role of the reduced... and degrading molecules are considered amphibolic Amphi is a Greek prefix meaning both 23 FIG 10: The CAC is amphibolic 24 SOURCES OF ACETYL-CoA 25 The skeleton drawings of the monosaccharide glucose, the fatty acid palmitic acid, Lecture Connections 16 | The Citric Acid Cycle © 2009 W H Freeman and Company CHAPTER 16 The Citric Acid Cycle Key topics: – Cellular respiration – Conversion of pyruvate to activated acetate – Reactions of the citric acid cycle – Regulation of the citric acid cycle – Conversion of acetate to carbohydrate precursors in the glyoxylate cycle Only a Small Amount of Energy Available in Glucose is Captured in Glycolysis Glycolysis G’° = -146 kJ/mol GLUCOSE Full oxidation (+ O2) G’° = -2,840 kJ/mol CO2 + H2O Cellular Respiration • process in which cells consume O2 and produce CO2 • provides more energy (ATP) from glucose than glycolysis • also captures energy stored in lipids and amino acids • evolutionary origin: developed about 2.5 billion years ago • used by animals, plants, and many microorganisms • occurs in three major stages: - acetyl CoA production - acetyl CoA oxidation - electron transfer and oxidative phosphorylation Respiration: Stage Generates some: ATP, NADH, FADH2 Respiration: Stage Generates more NADH, FADH2 and one GTP Respiration: Stage Makes lots of ATP Products from One Turn of the Cycle Net Effect of the Citric Acid Cycle Acetyl-CoA + 3NAD+ + FAD + GDP + Pi + H2O 2CO2 +3NADH + FADH2 + GTP + CoA + 3H+ • carbons of acetyl groups in acetyl-CoA are oxidized to CO2 • electrons from this process reduce NAD+ and FAD • one GTP is formed per cycle, this can be converted to ATP • intermediates in the cycle are not depleted Direct and Indirect ATP Yield Role of the Citric Acid Cycle in Anabolism Anaplerotic Reactions • these reactions replenish metabolites for the cycle • four carbon intermediates are formed by carboxylation of three-carbon precursors Regulation of the Citric Acid Cycle Glyoxylate Cycle Chapter 16: Summary In this chapter, we learned that: • Citric acid cycle is an important catabolic process: it makes GTP, and reduced cofactors that could yield ATP • Citric acid cycle plays important anabolic roles in the cell • A large multi-subunit enzyme, pyruvate dehydrogenase complex, converts pyruvate into acetyl-CoA • Several cofactors are involved in reactions that harness the energy from pyruvate • The rules of organic chemistry help to rationalize reactions in the citric acid cycle Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants A case study of endosymbiotic gene transfer Claus Schnarrenberger 1 and William Martin 2 1 Institut fu È r Biologie, Freie Universita È t Berlin, Germany; 2 Institut fu È r Botanik III, Universita È tDu È sseldorf, Germany The citric acid or tricarboxylic acid cycle is a central element of higher-plant carbon metabolism which p rovides, among other things, electrons for oxidative phosphorylation i n t he inner mitochondrial membrane, intermediates for amin o- acid biosynthesis, and oxaloacetate for gluconeogenesis from succinate derived from fatty acids via the glyoxylate cycle in g lyoxysomes. The tricarboxylic acid cycle is a typical mitochondrial pathway and is widespread among a-pro- teobacteria, the group of eubacteria as de®ned under rRNA systematics f rom w hich mitochondria arose. Most of the enzymes of the tricarboxylic acid cycle are encoded in the nucleus in higher eukaryotes, and several have been previ- ously shown to branch with their homologues from a-pro- teobacteria, indicating that the eukaryotic nuclear genes were acquired from the mitochondrial genome during the course of evolution. Here, we investigate the individual evolutionary histories o f all of the enzymes of the tricar- boxylic acid c ycle and the glyoxylate cycle using p rotein maximum likelihood phylogenies, focusing on t he evo lu- tionary origin of the nuclear-encoded proteins in higher plants. The results indicate that about half of the proteins involved in this eukaryo tic pathway a re most similar t o their a-proteobacterial homologues, whereas the remainder are most similar to eubacterial, but not speci®cally a-proteo- bacterial, homologues. A consideration of (a) the process of lateral gene transfer among free-living prokaryotes and ( b) the mechanistics of endosymbiotic (symbiont-to-host) gene transfer reveals that it i s unrealistic t o expect a ll nuclear genes that were acquired from the a-proteobacterial ancestor of mitochondria to branch speci®cally with their homologues encoded in the genomes o f contemporary a-proteobacteria. Rather, even if molecular phylogenetics were to work perfectly ( which i t does not), then some nuclear-encoded proteins that were acquired from the a-proteobacterial ancestor of mitochondria should, in phylogenetic t rees, branch with homologues that are no longer found in most a-proteobacterial genomes, and some should reside on long branches that reveal anity to eubacterial rather than archaebacterial homologues, but no particular anity for any speci®c eubacterial donor. Keywords: glyoxysomes; microbodies; mitochondria; pathway evolution, pyruvate dehydrogenase. Metabolic pathways are units of biochemical function that encompass a number of su bstrate conversions leading from one chemical intermediate to another. The large amounts of accumulated sequence data from prokaryotic and eukary- otic sources provide novel opportunities to study the molecular evolution not only o f individual enzymes, b ut also of individual pathways consisting of several enzymatic substrate conversions. This opens the door to a number of new and intriguing questions in m olecular e volution, s uch a s the following. Were pathways assembled originally during the early phases of biochemical evolution, and subsequently been passed down through inheritance ever since? Do pathways evolve as coherent entities consisting o f the same group Citric Acid Cycle and Oxidative Phosphorylation Citric Acid Cycle and Oxidative Phosphorylation Bởi: OpenStaxCollege The Citric Acid Cycle In eukaryotic cells, the pyruvate molecules produced at the end of glycolysis are transported into ... Pyruvate and the Citric Acid Cycle Link to Learning Click through each step of the citric acid cycle here Products of the Citric Acid Cycle Two carbon atoms come into the citric acid cycle from each... transfer their electrons to the 2/7 Oxidation of Pyruvate and the Citric Acid Cycle next pathway in the system, which will use oxygen If this transfer does not occur, the oxidation steps of the citric. .. which pyruvic acid is converted to acetyl CoA Then, the first step of the cycle begins: This 3/7 Oxidation of Pyruvate and the Citric Acid Cycle is a condensation step, combining the two-carbon