Sierra Acai Company
Sierra Acai Company
Open 7 Days a Week
MonaVie Independent Distributor
Distributor Training
Shop Online
Enroll Now
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
Friends
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
11-SEPTEMBER-2008 13:54:10 - acid cycle Overview of the citric acid cycle Overview of the citric acid cycle The citric acid cycle, also known as the tricarboxylic acid cycle TCA cycle or the Krebs cycle, or rarely, the Szent-Györgyi-Krebs cycle is a series of enzyme-catalysed chemical reactions of central importance in all living cells that use oxygen as part of cellular respiration. In eukaryotes, the citric acid cycle occurs in the matrix of the mitochondrion. The components and reactions of the citric acid cycle were established by seminal work from both Albert Szent-Györgyi and Hans Krebs. In aerobic organisms, the citric acid cycle is part of a metabolic pathway involved in the chemical conversion of carbohydrates, fats and proteins into carbon dioxide and water to generate a form of usable energy. Other relevant reactions in the pathway include those in glycolysis and pyruvate oxidation before the citric acid cycle, and oxidative phosphorylation after it. In addition, it provides precursors for many compounds including some amino acids and is therefore functional even in cells performing fermentation. Contents 1 Overview 2 A simplified view of the process 3 Products 4 Regulation 5 Major metabolic pathways converging on the TCA cycle 6 See also 7 Notes 8 References 9 External links Overview Two carbons are oxidized to CO2, and the energy from these reactions is transferred to other metabolic processes by GTP or ATP, and as electrons in NADH and QH2. The NADH generated in the TCA cycle may later donate its electrons in oxidative phosphorylation to drive ATP synthesis; FADH2 is covalently attached to succinate dehydrogenase, an enzyme functioning both in the TCA cycle and the mitochondrial electron transport chain in oxidative phosphorylation. FADH2 thereby facilitates transfer of electrons to coenzyme Q, which is the final electron acceptor of the reaction catalyzed by the Succinate:ubiquinone oxidoreductase complex, also acting as an intermediate in the electron transport chain.1 The citric acid cycle is continuously supplied new carbons in the form of acetyl-CoA, entering at step 1 below.2 Substrates Products Enzyme Reaction type Comment 1 Oxaloacetate + Acetyl CoA + H2O Citrate + CoA-SH Citrate synthase Aldol condensation rate limiting stage, extends the 4C oxaloacetate to a 6C molecule 2 Citrate cis-Aconitate + H2O Aconitase Dehydration reversible isomerisation 3 cis-Aconitate + H2O Isocitrate Hydration 4 Isocitrate + NAD+ Oxalosuccinate + NADH + H + Isocitrate dehydrogenase Oxidation generates NADH equivalent of 2.5 ATP 5 Oxalosuccinate α-Ketoglutarate + CO2 Decarboxylation irreversible stage, generates a 5C molecule 6 α-Ketoglutarate + NAD+ + CoA-SH Succinyl-CoA + NADH + H+ + CO2 α-Ketoglutarate dehydrogenase Oxidative decarboxylation generates NADH equivalent of 2.5 ATP, regenerates the 4C chain CoA excluded 7 Succinyl-CoA + GDP + Pi Succinate + CoA-SH + GTP Succinyl-CoA synthetase substrate level phosphorylation or ADP-ATP,1 generates 1 ATP or equivalent 8 Succinate + ubiquinone Q Fumarate + ubiquinol QH2 Succinate dehydrogenase Oxidation uses FAD as a prosthetic group FAD-FADH2 in the first step of the reaction in the enzyme,1 generates the equivalent of 1.5 ATP 9 Fumarate + H2O L-Malate Fumarase H2O addition hydration 10 L-Malate+ NAD+ Oxaloacetate + NADH + H+ Malate dehydrogenase Oxidation generates NADH equivalent of 2.5 ATP Mitochondria in animals including humans possess two succinyl-CoA synthetases, one that produces GTP from GDP, and another that produces ATP from ADP.3 Plants have the type that produces ATP ADP-forming succinyl-CoA synthetase.2 The GTP that is formed by GDP-forming succinyl-CoA synthetase may be utilized by nucleoside-diphosphate kinase to form ATP the catalyzed reaction is GTP + ADP - GDP + ATP.1 A simplified view of the process The citric acid cycle begins with acetyl-CoA transferring its two-carbon acetyl group to the four-carbon acceptor compound oxaloacetate to form a six-carbon compound citrate. The citrate then goes through a series of chemical transformations, losing first one, then a second carboxyl group as CO2. The carbons lost as CO2 originate from what was oxaloacetate, not directly from acetyl-CoA. The carbons donated by acetyl-CoA become part of the oxaloacetate carbon backbone after the first turn of the citric acid cycle. Loss of the acetyl-CoA-donated carbons as CO2 requires several turns of the citric acid cycle. However, because of the role of the citric acid cycle in anabolism, they may not be lost since many TCA cycle intermediates are also used as precursors for the biosynthesis of other molecules.4 Most of the energy made available by the oxidative steps of the cycle is transferred as energy-rich electrons to NAD+, forming NADH. For each acetyl group that enters the citric acid cycle, three molecules of NADH are produced. Electrons are also transferred to the electron acceptor Q, forming QH2. At the end of each cycle, the four-carbon oxaloacetate has been regenerated, and the cycle continues. Products Products of the first turn of the cycle are: one GTP or ATP, three NADH, one QH2, two CO2. Because two acetyl-CoA molecules are produced from each glucose molecule, two cycles are required per glucose molecule. Therefore, at the end of all cycles, the products are: two GTP, six NADH, two QH2, and four CO2 Description Reactants Products The sum of all reactions in the citric acid cycle is: Acetyl-CoA + 3 NAD+ + Q + GDP + Pi + 2 H2O → CoA-SH + 3 NADH + 3 H+ + QH2 + GTP + 2 CO2 Combining the reactions occurring during the pyruvate oxidation with those occurring during the citric acid cycle, the following overall pyruvate oxidation reaction is obtained: Pyruvic acid + 4 NAD+ + Q + GDP + Pi + 2 H2O → 4 NADH + 4 H+ + QH2 + GTP + 3 CO2 Combining the above reaction with the ones occurring in the course of glycolysis, the following overall glucose oxidation reaction excluding reactions in the respiratory chain is obtained: Glucose + 10 NAD+ + 2 Q + 2 ADP + 2 GDP + 4 Pi + 2 H2O → 10 NADH + 10 H+ + 2 QH2 + 2 ATP + 2 GTP + 6 CO2 the above reactions are equilibrated if Pi represents the H2PO4- ion, ADP and GDP the ADP2- and GDP2- ions, respectively, and ATP and GTP the ATP3- and GTP3- ions, respectively. Estimates for the total number of ATP obtained after complete oxidation of one glucose in glycolysis, citric acid cycle, and oxidative phosphorylation given in the literature range from 30-38 molecules of ATP. A recent assessment of the total ATP yield obtained in these distinct reaction cycles, taking into account updated proton-to-ATP ratios, has arrived at an estimate of 29.85 ATP per glucose molecule. 5 Regulation Although pyruvate dehydrogenase is not technically a part of the citric acid cycle, its regulation is included here. The regulation of the TCA cycle is largely determined by substrate availability and product inhibition. NADH, a product of all dehydrogenases in the TCA cycle with the exception of succinate dehydrogenase, inhibits pyruvate dehydrogenase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, and also citrate synthase. Acetyl-CoA inhibits pyruvate dehydrogenase, while succinyl-CoA inhibits succinyl-CoA synthase and citrate synthase. When tested in vitro with TCA enzymes, ATP inhibits citrate synthase and α-ketoglutarate dehydrogenase; however, ATP levels do not change more than 10% in vivo between rest and vigorous exercise. There is no known allosteric mechanism that can account for large changes in reaction rate from an allosteric effector whose concentration changes less than 10% 6. Calcium is used as a regulator. It activates pyruvate dehydrogenase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase.7 This increases the reaction rate of many of the steps in the cycle, and therefore increases flux throughout the pathway. Citrate is used for feedback inhibition, as it inhibits phosphofructokinase, an enzyme involved in glycolysis that catalyses formation of fructose 1,6-bisphosphate, a precursor of pyruvate. This prevents a constant high rate of flux when there is an accumulation of citrate and a decrease in substrate for the enzyme. Recent work has demonstrated an important link between intermediates of the citric acid cycle and the regulation of hypoxia inducible factors HIF. HIF plays a role in the regulation of oxygen haemostasis, and is a transcription factor which targets angiogenesis, vascular remodelling, glucose ulitisation, iron transport and apoptosis. HIF is synthesized consititutively and hydroxylation of at least one of two critical proline residues mediates their interaction with the von Hippel Lindau E3 ubiquitin ligase complex which targets them for rapid degradation. This reaction is calalysed by prolyl 4-hydroxylases. Fumarate and succinate have been identified as potent inhibitors of prolyl hydroxylases thus leading to the stabilisation of HIF.8 Major metabolic pathways converging on the TCA cycle Several catabolic pathways converge on the TCA cycle. Reactions that form intermediates of the TCA cycle in order to replenish them especially during the scarcity of the intermediates are called anaplerotic reactions. The citric acid cycle is the third step in carbohydrate catabolism the breakdown of sugars. Glycolysis breaks glucose a six-carbon-molecule down into pyruvate a three-carbon molecule. In eukaryotes, pyruvate moves into the mitochondria. It is converted into acetyl-CoA by decarboxylation and enters the citric acid cycle. In protein catabolism, proteins are broken down by protease enzymes into their constituent amino acids. The carbon backbone of these amino acids can become a source of energy by being converted to Acetyl-CoA and entering into the citric acid cycle. In fat catabolism, triglycerides are hydrolyzed to break them into fatty acids and glycerol. In the liver the glycerol can be converted into glucose via dihydroxyacetone phosphate and glyceraldehyde-3-phosphate by way of gluconeogenesis. In many tissues, especially heart tissue, fatty acids are broken down through a process known as beta oxidation which results in acetyl-CoA which can be used in the citric acid cycle. Beta oxidation of odd chain fatty acids can yield propionyl CoA which can result in further glucose production by gluconeogenesis in the liver. The citric acid cycle is always followed by oxidative phosphorylation. This process extracts the energy as electrons from NADH and QH2, oxidizing them to NAD+ and Q, respectively, so that the cycle can continue. Whereas the citric acid cycle does not use oxygen, oxidative phosphorylation does. The total energy gained from the complete breakdown of one molecule of glucose by glycolysis, the citric acid cycle and oxidative phosphorylation equals about 30 ATP molecules, in eukaryotes. The citric acid cycle is called an amphibolic pathway because it participates in both catabolism and anabolism. See also Calvin cycle Oxidative decarboxylation Citric acid Glycolysis Pyruvate decarboxylation Oxidative phosphorylation Reverse Reductive Krebs cycle Glyoxylate cycle Hans Adolf Krebs Notes ^ a b c d Berg, JM; JL Tymoczko, L Stryer 2002. Biochemistry - 5th ion. WH Freeman and Company, 465-484, 498-501. ISBN 0-7167-4684-0. ^ a b Buchanan; Gruissem, Jones 2000. Biochemistry molecular biology of plants, 1st ion, American society of plant physiology. ISBN 0-943088-39-9. ^ Johnson JD, Mehus JG, Tews K, Milavetz BI, Lambeth DO 1998. Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes. J Biol Chem 273 42: 27580-6. doi:10.1074/jbc.273.42.27580. PMID 9765291. ^ Wolfe RR, Jahoor F. 1990 Recovery of labeled CO2 during the infusion of C-1- vs C-2-labeled acetate: implications for tracer studies of substrate oxidation. Am J Clin Nutr. 512:248-52. PMID 2106256 ^ Rich PR 2003. The molecular machinery of Keilin's respiratory chain. Biochem. Soc. Trans. 31 Pt 6: 1095-105. doi:10.1074/jbc.X200011200. PMID 14641005. ^ Voet, D. Voet, J. G. 2004 Biochemistry 3rd ion John Wiley Sons, Inc., New York p. 615 ^ Denton RM; Randle PJ, Bridges BJ, Cooper RH, Kerbey AL, Pask HT, Severson DL, Stansbie D, Whitehouse S. Oct 1975. Regulation of mammalian pyruvate dehydrogenase. Mol Cell Biochem 9 1: 27-53. doi:10.1007/BF01731731. ^ Koivunen P, Hirsilä M, Remes AM, Hassinen IE, Kivirikko KI, Myllyharju J 2007. Inhibition of hypoxia-inducible factor HIF hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J. Biol. Chem. 282 7: 4524-32. doi:10.1074/jbc.M610415200. PMID 17182618. References Neil A. Campbell; Jane B. Reece Dec 2005. Biology, 7th ed., Benjamin Cummings. ISBN 978-0805371468. Solomon, E.P.; Berg, L.R., Martin, D.W. Mar 2005. Biology. Brooks Cole. ISBN 978-0534495480. External links An animation of the citric acid cycle at Smith College A video of members of The Ohio State Marching Band enacting the Krebs cycle at YouTube Notes on citric acid cycle at rahulgladwin.com A more detailed tutorial animation at johnkyrk.com A citric-acid cycle self quiz flash applet at University of Pittsburgh The chemical logic behind the citric acid cycle at ufp.pt v d e Major subfields of biology Anatomy · Astrobiology · Biochemistry · Bioinformatics · Biostatistics · Botany · Cell biology · Chronobiology · Developmental biology · Ecology · Epidemiology · Evolutionary biology · Genetics · Genomics · Human biology · Immunology · Marine biology · Microbiology · Molecular biology · Neuroscience · Nutrition · Origin of life · Paleontology · Parasitology · Pathology · Physiology · Systems biology · Taxonomy · Zoology v d e Cellular Respiration Aerobic Respiration Glycolysis → Pyruvate Decarboxylation → Citric Acid Cycle → Oxidative Phosphorylation Electron Transport Chain + ATP synthase Anaerobic Respiration Glycolysis → Lactic Acid Formation or Ethanol Formation v d e Citric Acid Cycle Metabolic Pathway Oxaloacetate Malate Fumarate Succinate Succinyl-CoA Acetyl-CoA NADH + H+ NAD+ H2O FADH2 FAD CoA + ATPGTP Pi + ADPGDP + H2O NADH + H+ + CO2 CoA NAD+ H2O H2O NADP+ NADPH + H+ CO2 Citrate cis-Aconitate Isocitrate Oxalosuccinate α-Ketoglutarate v d e Metabolism map Glucuronate metabolism Pentose interconversion Inositol metabolism Cellulose and sucrose metabolism Starch and glycogen metabolism Other sugar metabolism Pentose phosphate pathway Glycolysis and Gluconeogenesis Amino sugars metabolism Small amino acid synthesis Branched amino acid synthesis Purine biosynthesis Histidine metabolism Aromatic amino acid synthesis Pyruvate decarboxylation Anaerobic respiration Fatty acid metabolism Urea cycle Aspartate amino acid group synthesis Porphyrins and corrinoids metabolism Citric acid cycle Glutamate amino acid group synthesis Pyrimidine biosynthesis v d e All pathway labels on this image are links, simply click to access the article. A high resolution labeled version of this image is available here. v d e Metabolism: Citric acid cycle enzymes Cycle Citrate synthase - Aconitase - Isocitrate dehydrogenase - Oxoglutarate dehydrogenase - Succinyl CoA synthetase Succinate dehydrogenase SDHA - Fumarase - Malate dehydrogenase Anaplerotic to acetyl-CoA: Pyruvate dehydrogenase complex regulated by Pyruvate dehydrogenase kinase and Pyruvate dehydrogenase phosphatase to ketoglutaric acid: Glutamate dehydrogenase to succinyl-CoA: Methylmalonyl-CoA mutase to oxaloacetate: Pyruvate carboxylase - Aspartate transaminase Retrieved from http://en..org/wiki/Citric_acid_cycle Categories: Citric acid cycle | Cellular respiration | Exercise physiology | Metabolic pathways Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages العربية БългарÑ?ки ÄŒesky Dansk Deutsch Español Esperanto Français í•œêµì–´ Hrvatski Italiano עברית LatvieÅ¡u Lëtzebuergesch Lietuvių Magyar МакедонÑ?ки Bahasa Melayu Nederlands 日本語 ‪Norsk bokmÃ¥l‬ Occitan پښتو Polski Português РуÑ?Ñ?кий SlovenÄ?ina SlovenÅ¡Ä?ina СрпÑ?ки / Srpski Basa Sunda Suomi Svenska Tagalog ไทย Tiếng Việt Türkçe УкраїнÑ?ька ä¸æ–‡ This page was last modified on 10 August 2008, at 04:1
39 Reasons to Drink Acai Juice Every Day
What is MonaVie - Watch the 8-minute video
Discovering MonaVie Video
The Power of You Video
Effects of MonaVie Active on Antioxidant Capacity in Humans
So many of us do not eat a balanced diet, get enough sleep, have too much stress, or are impacted with toxins and pollutants. Drinking 2 ounces of MonaVie twice a day will help your body detoxify as well as build your immune system. Its the smartest thing you can do for yourself, so start today. Buying MonaVie through our company guarantees you support 7 days a week and, if you would like to share MonaVie with your family and friends we will guide you from start to finish.
1. Click on Enroll Now (30 - 55% off retail price)
2. Pay $39 for your Wholesale ID number.
3. NO minimum order required.
4. MonaVie is delivered to your door in 3 to 5 days.