DOCSLIB.ORG

Citric Acid Cycle

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Citric Acid Cycle CITRIC ACID CYCLE CLASS – B.Sc. PART-III(HONS.) BY KUNDAN PATEL GUEST FACULTY DEPARTMNET OF ZOOLOGY, B.N. COLLEGE, PATNA INTRODUCTION Citric acid cycle or Krebs cycle is a sequence of reactions occurring in mitochondria during aerobic respiration through which the Pyruvate, produced after glycolysis, is oxidised to CO2 & H2O. The energy released during the process is conserved in reduced electron carriers like NADH & FADH2 which are again oxidised during electron transport and its energy is conserved in ATP. It was identified by Hans Adolf Krebs in 1937 and hence also named as Krebs cycle. PRODUCTION OF ACETYL CO-A ● Pyruvate is oxidised to acetyl Co-A by the enzyme Pyruvate Dehydrogenase(PDH) complex which is a complex of multiple copies of each of the three enzymes - E1, E2 & E3 – located in the mitochondria of eukaryotes and in the cytosol of prokaryotes. ● This reaction involves five coenzymes – thiamine pyrophosphate(TPP), FAD, NAD, Coenzyme A and lipoate. ● E1 = Pyruvate Dehydrogenase ● E2 = Dihydrolipoyl Transacetylase ● E3 = Dihydrolipoyl Dehydrogenase PRODUCTION OF ACETYL CO-A PRODUCTION OF ACETYL CO-A REACTIONS OF KREBS CYCLE 1. Formation of Citrate:- ● Condensation of Acetyl-CoA with Oxaloacetate results in the formation of Citrate ● It is catalysed by Citrate synthase REACTIONS OF KREBS CYCLE 2. Formation of Isocitrate:- ● Citrate is reversively transformed to Isocitrate via the intermediary formation of the cis- aconitate ● It is catalysed by the enzyme Aconitase REACTIONS OF KREBS CYCLE 3. Oxidation of isocitrate to α- Ketoglutarate:- ● The enzyme Isocitrate dehydrogenase catalyses the oxidative decarboxylation of Isocitrate to form α- Ketoglutarate via an intermediate Oxalosuccinate ● NAD+ acts as electron acceptor REACTIONS OF KREBS CYCLE 4.Oxidation of α- Ketoglutarate to Succinyl-CoA:- ● The enzyme α- Ketoglutarate dehydrogenase complex catalyses the oxidative decarboxylation of α- Ketoglutarate to form Succinyl-CoA ● NAD+ acts as electron acceptor REACTIONS OF KREBS CYCLE 5. Conversion of Succinyl-CoA to Succinate:- ● This reversible reaction is catalysed by Succinyl-CoA synthetase ● GDP is phosphorylated to GTP REACTIONS OF KREBS CYCLE 6. Oxidation of Succinate to Fumarate:- ● This reversible reaction is catalysed by Succinate dehydrogenase ● FAD acts as electron acceptor and is converted to FADH2 REACTIONS OF KREBS CYCLE 7. Hydration of Fumarate to Malate: - ● This reversible reaction is catalysed by Fumarase REACTIONS OF KREBS CYCLE 8. Oxidation of Malate to Oxaloacetate:- ● This is the last reaction catalysed by Malate dehydrogenase ● NAD+ acts as electron acceptor in this reversible reaction REACTIONS OF KREBS CYCLE ENERGETICS S.NO. REACTION NO. OF ATP OR NO. OF ATP REDUCED ULTIMATELY COENZYMES FORMED DIRECTLY FORMED 1. Formation of Acetyl- 1 NADH 2.5 ATP CoA from Pyruvate 2. Oxidation of Isocitrate 1 NADH 2.5 ATP to α-Ketoglutarate 3. Oxidation of α- 1 NADH 2.5 ATP Ketoglutarate to Succinyl-CoA 4. Conversion of Succinyl- 1 GTP 1 ATP CoA to Succinate 5. Oxidation of Succinate 1 FADH2 1.5 ATP to Fumarate 6. Oxidation of Malate to 1 NADH 2.5 ATP Oxaloacetate SIGNIFICANCE OF THE CYCLE 1. The energy during the oxidations are conserved in the reduction of three NAD+ and one FAD and the production of one ATP or GTP 2. At the end of the cycle oxaloacetate is regenerated but the two carbon atoms appearing as CO2 are not the same two carbons that entered in the form of the acetyl group 3. Although this cycle directly generates only one ATP per turn, the four oxidation steps in the cycle provide a large flow of electrons into the respiratory chain via NADH and FADH2 and thus lead to the formation of a large number of ATP molecules during oxidative phosphorylation 4. It is an amphibolic pathway that plays an important role in oxidative catabolism of carbohydrates , amino acids and fatty acids on one hand and on the other provides precursors for many biosynthetic pathways CONCLUSION It can be concluded that citric acid cycle or Krebs cycle is an efficient mechanism to conserve the energy in the form of reduced electron carriers that further feed up the respiratory chain so that a cell can extract maximum of the energy hidden in its fuel substrates. Being amphibolic in nature it serves the purpose of catabolism and anabolism required in a cell. BIBLIOGRAPHY & REFERENCES ● Lehninger Principles of Biochemistry(W.H. Freeman and Co., New York) ● Biochemistry(Berg, Tymoczko & Stryer) ● Harper’s Illustrated Biochemistry(TMHCompanies Inc.) ● Biochemistry(M.C. Pant) THANK YOU.
Load more

Recommended publications
  • Amphibolic Nature of Krebs Cycle
    Amphibolic nature of Krebs Cycle How what we are is what we eat • In aerobic organisms, the citric acid cycle is an amphibolic pathway, one that serves in both catabolic and anabolic processes. • Since the citric acid does both synthesis (anabolic) and breakdown (catabolic) activities, it is called an amphibolic pathway • The citric acid cycle is amphibolic (i.e it is both anabolic and catabolic in its function). • It is said to be an AMPHIBOLIC pathway, because it functions in both degradative or catabolic and biosynthetic or anabolic reactions (amphi = both) A central metabolic pathway or amphibolic pathway is a set of reactions which permit the interconversion of several metabolites, and represents the end of the catabolism and the beginning of anabolism • The KREBS CYCLE or citric acid cycle is a series of reactions that degrades acetyl CoA to yield carbon dioxide, and energy, which is used to produce NADH, H+ and FADH. • The KREBS CYCLE connects the catabolic pathways that begin with the digestion and degradation of foods in stages 1 and 2 with the oxidation of substrates in stage 3 that generates most of the energy for ATP synthesis. • The citric acid cycle is the final common pathway in the oxidation of fuel molecules. In stage 3 of metabolism, citric acid is a final common catabolic intermediate in the form of acetylCoA. • This is why the citric acid cycle is called a central metabolic pathway. Anaplerosis and Cataplerosis Anaplerosis is a series of enzymatic reactions in which metabolic intermediates enter the citric acid cycle from the cytosol. Cataplerosis is the opposite, a process where intermediates leave the citric acid cycle and enter the cytosol.
    [Show full text]
  • Exam #2 Review
    Exam #2 Review Exam #2 will cover all the material that has been presented in class since Exam #1 and up through the metabolism introduction. This includes eukaryotic cell structure / function, transport, the closed system growth curve, enzymes and the introduction to metabolism. As always, it is best to begin by studying your notes and then after you feel your study is complete, take some time to look through this review. I. Eukaryotic cell structure / function A. There is a great deal of variance among eukaryotic cells - from protozoan cells to yeast cells to human cells. Fungi and protists (classically split into algae and protozoa) are eukaryotic representatives of the microbial world. B. Structure of the eukaryotic cell. 1. Cytoskeleton - provides structure and shape of cell, three components: a. Microtubules - largest element of cytoskeleton, composed of hollow cylinders of tubulin, form mitotic spindles, cilia and flagella and cell “highways”. b. Microfilaments - smallest element of cytoskeleton, composed of actin, involved in motion (pseudopod formation). c. Intermediate filaments - very stable structural element, play a supportive role, composed of proteins including keratin. Practice: Microfilaments a. are a component of the cytoskeleton. b. are long, twisted polymers of a protein called actin. c. form eukaryotic flagella. d. are made of tubulin. e. a and b f. c and d 2. Nucleus a. Bound by both an inner and outer membrane. The space between the two membranes is called the perinuclear space. The membrane has large nuclear pores through which proteins can pass (Why is this important?) b. Linear pieces of DNA are packaged by wrapping one and three quarters times around a histone octamer to form a core particle.
    [Show full text]
  • Fatty Acid Biosynthesis
    BI/CH 422/622 ANABOLISM OUTLINE: Photosynthesis Carbon Assimilation – Calvin Cycle Carbohydrate Biosynthesis in Animals Gluconeogenesis Glycogen Synthesis Pentose-Phosphate Pathway Regulation of Carbohydrate Metabolism Anaplerotic reactions Biosynthesis of Fatty Acids and Lipids Fatty Acids contrasts Diversification of fatty acids location & transport Eicosanoids Synthesis Prostaglandins and Thromboxane acetyl-CoA carboxylase Triacylglycerides fatty acid synthase ACP priming Membrane lipids 4 steps Glycerophospholipids Control of fatty acid metabolism Sphingolipids Isoprene lipids: Cholesterol ANABOLISM II: Biosynthesis of Fatty Acids & Lipids 1 ANABOLISM II: Biosynthesis of Fatty Acids & Lipids 1. Biosynthesis of fatty acids 2. Regulation of fatty acid degradation and synthesis 3. Assembly of fatty acids into triacylglycerol and phospholipids 4. Metabolism of isoprenes a. Ketone bodies and Isoprene biosynthesis b. Isoprene polymerization i. Cholesterol ii. Steroids & other molecules iii. Regulation iv. Role of cholesterol in human disease ANABOLISM II: Biosynthesis of Fatty Acids & Lipids Lipid Fat Biosynthesis Catabolism Fatty Acid Fatty Acid Degradation Synthesis Ketone body Isoprene Utilization Biosynthesis 2 Catabolism Fatty Acid Biosynthesis Anabolism • Contrast with Sugars – Lipids have have hydro-carbons not carbo-hydrates – more reduced=more energy – Long-term storage vs short-term storage – Lipids are essential for structure in ALL organisms: membrane phospholipids • Catabolism of fatty acids –produces acetyl-CoA –produces reducing
    [Show full text]
  • Citric Acid Cycle
    CHEM464 / Medh, J.D. The Citric Acid Cycle Citric Acid Cycle: Central Role in Catabolism • Stage II of catabolism involves the conversion of carbohydrates, fats and aminoacids into acetylCoA • In aerobic organisms, citric acid cycle makes up the final stage of catabolism when acetyl CoA is completely oxidized to CO2. • Also called Krebs cycle or tricarboxylic acid (TCA) cycle. • It is a central integrative pathway that harvests chemical energy from biological fuel in the form of electrons in NADH and FADH2 (oxidation is loss of electrons). • NADH and FADH2 transfer electrons via the electron transport chain to final electron acceptor, O2, to form H2O. Entry of Pyruvate into the TCA cycle • Pyruvate is formed in the cytosol as a product of glycolysis • For entry into the TCA cycle, it has to be converted to Acetyl CoA. • Oxidation of pyruvate to acetyl CoA is catalyzed by the pyruvate dehydrogenase complex in the mitochondria • Mitochondria consist of inner and outer membranes and the matrix • Enzymes of the PDH complex and the TCA cycle (except succinate dehydrogenase) are in the matrix • Pyruvate translocase is an antiporter present in the inner mitochondrial membrane that allows entry of a molecule of pyruvate in exchange for a hydroxide ion. 1 CHEM464 / Medh, J.D. The Citric Acid Cycle The Pyruvate Dehydrogenase (PDH) complex • The PDH complex consists of 3 enzymes. They are: pyruvate dehydrogenase (E1), Dihydrolipoyl transacetylase (E2) and dihydrolipoyl dehydrogenase (E3). • It has 5 cofactors: CoASH, NAD+, lipoamide, TPP and FAD. CoASH and NAD+ participate stoichiometrically in the reaction, the other 3 cofactors have catalytic functions.
    [Show full text]
  • Pyruvate Dehydrogenase
    Aerobic Metabolism I: The Citric Acid Cycle Chapter 9 Overview n Live processes - series of oxidation-reduction reactions ¨ Ingestion of proteins, carbohydrates, lipids ¨ Provide basic building blocks for major molecules ¨ Produces energy n Aerobic metabolism I ¨ Citric Acid Cycle – series of reactions that release chemical energy stored in acetyl-CoA n Acetyl-CoA derived from pyruvate From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press Chapter 9: Overview §Citric acid cycle §Two-carbon fragments oxidized to form CO2 + §NAD /FAD reduced to NADH/FADH2 §Electron transport chain §Transfer of electrons from NADH/FADH2 to electron carriers §Terminal acceptor O2 §Oxidative phosphorylation §Energy released forms proton gradient §Drives ATP synthesis Figure 9.1 Overview of Aerobic Metabolism From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press Section 9.1: Oxidation-Reduction Reactions Figure 9.3 Reduction of Pyruvate by NADH §Redox reactions – electron transfer between an electron donor (reducing agent) & electron acceptor (oxidizing agent) §Many redox reactions have both an electron (e-) and a proton (H+) transferred §Conversion of pyruvate and NADH to lactate and NAD+ (shown above) is under anaerobic conditions From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press Section 9.1: Oxidation-Reduction Reactions §Half-reactions of redox reactions Cu loses e-, electron donor Cu+ ß à Cu2+ + e- Fe gains e-, electron acceptor Fe3+ + e- ß à Fe2+ Figure 9.4 An Electrochemical
    [Show full text]
  • Catabolism of the Carbon Skeletons of Amino Acids
    Bio. 2. ASPU. Lectu.3. Prof. Dr. F. ALQuobaili Catabolism of the Carbon Skeletons of Amino Acids • Biomedical Importance ‐ The metabolic diseases or "inborn errors of metabolism" associated with conversion of the carbon skeletons of the common L ‐‐amino acids to amphibolic intermediates can result in irreversible brain damage and .(ﺍﻟﻭﻓﺎﺓ) early mortality ‐ Prenatal or early postnatal detection and timely initiation of treatment thus are essential. Almost all states conduct screening tests for up to as many as 30 metabolic diseases. ‐ The best screening tests use tandem mass spectrometry to detect, in a few drops of neonate blood, catabolites suggestive of a metabolic defect. ‐ Treatment consists primarily of feeding diets low in the amino acids whose catabolism is impaired. • Transamination Typically Initiates Amino Acid Catabolism Removal of ‐amino nitrogen by transamination is the first catabolic reaction of amino acids except for proline, hydroxyproline, threonine, and lysine. The hydrocarbon skeleton that remains is then degraded to amphibolic intermediates. • Asparagine, Aspartate, Glutamine, and Glutamate All four carbons of asparagine and aspartate form oxaloacetate. Analogous reactions convert glutamine and glutamate to ‐ ketoglutarate. No metabolic defects are associated with the catabolism of these four amino acids. • Proline The catabolism of proline takes place in mitochodria. Since proline does not participate in transamination, the nitrogen of this imino acid is retained throughout its oxidation to 1‐ pyrolline‐5‐carboxylate, ring opening to glutamate‐‐ semialdehyde, and oxidation to glutamate, and is only removed during transamination of glutamate to ‐ketoglutarate. There are two metabolic disorders of proline catabolism. Both types are inherited as autosomal recessive traits, and are consistent with a normal adult life.
    [Show full text]
  • Cellular Stress Created by Intermediary Metabolite Imbalances
    Cellular stress created by intermediary metabolite imbalances Sang Jun Leea, Andrei Trostela, Phuoc Lea, Rajendran Harinarayananb, Peter C. FitzGeraldc, and Sankar Adhyaa,1 aLaboratory of Molecular Biology, National Cancer Institute, bLaboratory of Molecular Genetics, National Institute of Child Health and Human Development, and cGenome Analysis Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 Contributed by Sankar Adhya, September 16, 2009 (sent for review July 14, 2009) Small molecules generally activate or inhibit gene transcription as pathway. Accumulation of this intermediate was known to cause externally added substrates or as internally accumulated end- stress, stop cell growth, and cause cell lysis in complex medium products, respectively. Rarely has a connection been made that (7–9). Using UDP-galactose as an example, we report here (i) links an intracellular intermediary metabolite as a signal of gene that an amphibolic operon is controlled both by the substrate of expression. We report that a perturbation in the critical step of a the pathway and an intermediary product, (ii) how the interme- metabolic pathway—the D-galactose amphibolic pathway— diary metabolite accumulation causes cellular stress and sends changes the dynamics of the pathways leading to accumulation of signals to genetic level, and (iii) how the latter overcomes the the intermediary metabolite UDP-galactose. This accumulation stress to achieve homeostasis. causes cell stress and transduces signals that alter gene expression so as to cope with the stress by restoring balance in the metabolite Results and Discussion pool. This underscores the importance of studying the global D-galactose-Dependent Growth Arrest of gal Mutants.
    [Show full text]
  • Biochemistry Anabolism of Lipids
    Paper : 05 Metabolism of Lipids Module: 12 Anabolism of Lipids Principal Investigator Dr. Sunil Kumar Khare, Professor, Department of Chemistry, IIT-Delhi Dr. Vijaya Khader Dr. MC Varadaraj Paper Coordinator and Dr. Suaib Luqman, Scientist (CSIR-CIMAP) Content Writer & Assistant Professor (AcSIR) CSIR -CIMAP, Lucknow Content Reviewer Prof. Prashant Mishra, Professor, Department of Biochemical Engineering and Biotechnology, IIT-Delhi 1 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids DESCRIPTION OF MODULE Subject Name Biochemistry Paper Name 05 Metabolism of Lipids Module Name/Title 12 Lipids-Anabolism 2 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids 1. Objectives To understand the anabolism of lipids What are the implications of lipid anabolism 2. Concept Map 3 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids 4 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids 3. Description Anabolism is the word derived from the Greek (Ana-upward and Bolism-to throw) meaning a process that have a propensity to build up tissues and organs. It is an array of metabolic pathways that assemble molecules from smaller units and the process engender differentiation and growth of cells and augmentation in body size (e.g. growth and mineralization of bone and increase in muscle mass). The reactions in anabolism entail and utilize energy released by catabolism to synthesize complex molecules which further employed to form cellular 5 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids structures from simple and small precursors that act as building blocks. Numerous anabolic processes are power- driven by the hydrolysis of adenosine triphosphate (ATP). Following are the fundamental defined stages of anabolism. 1. Assembly of precursors such as fatty acids, amino acids, isoprenoids, monosaccharides and nucleotides.
    [Show full text]
  • Biochemistry Metabolism
    Biochemistry Metabolism 22.11.2018 – 11.12.2018 The fate of pyruvate Citrate cycle Gerhild van Echten-Deckert Tel. 73 2703 E-mail: [email protected] www.limes-institut-bonn.de Utilization of pyruvate pyruvate pyruvate decarboxylase lactate dehydrogenase dehydrogenase Berg, Tymoczko, Stryer: Biochemistry Thiamine pyrophosphate (TPP), the cofactor of pyruvate decarboxylase Also co-factor of: pyruvate-DH, -ketoglutarate-DH, transketolase Thiamine, vitamin B1 Deficiency: Beriberi disease Catalytic Mechanism of Pyruvate Decarboxylase Beriberi – deficiency of thiamine (vit. B1) • There are two major types of beriberi: – Wet beriberi affects the cardiovascular system. – rare in the United States because most foods are now vitamin enriched. – Dry beriberi/Wernicke Korsakoff syndrome affects the nervous system. • Today, beriberi occurs mostly in patients who abuse alcohol. Ethanol interferes with thiamine uptake in the gastrointestinal tract, its storage in the liver and its transformation in the active form (pyrophosphate). Moreover, drinking heavily can lead to poor nutrition and makes it harder to eat. • Beriberi can occur in breast-fed infants when the mother's body is lacking in thiamine. The condition can also affect infants who are fed unusual formulas that don't have enough thiamine. • Getting dialysis and taking high doses of diuretics raise the risk of Beriberi. Dry and wet Beriberi: Symptoms • Symptoms of dry beriberi: affects the nervous system. Wernicke- Korsakoff syndrome is a brain disorder caused by thiamine deficiency that results in a number of neurologic symptoms and can lead to psychosis, confusion and hallucinations. Difficulty walking; loss of feeling in hands and feet; loss of muscle function or paralysis of the lower legs; mental confusion/speech difficulties; pain; strange eye movements (nystagmus); tingling; vomiting • Symptoms of wet beriberi: affects the cardiovascular system; awakening at night short of breath; increased heart rate; shortness of breath with activity; swelling of the lower legs.
    [Show full text]
  • ANABOLISM III: Biosynthesis Amino Acids & Nucleotides
    BI/CH 422/622 ANABOLISM OUTLINE: Photosynthesis Carbohydrate Biosynthesis in Animals Biosynthesis of Fatty Acids and Lipids Biosynthesis of Amino Acids and Nucleotides Nitrogen fixation nitrogenase Nitrogen assimilation Glutamine synthetase Glutamate synthase Amino-acid Biosynthesis non-essential essential Nucleotide Biosynthesis RNA precursors purines pyrimidines DNA precursors deoxy-nucleotides Biosynthesis of secondary products of amino acids ANABOLISM III: Biosynthesis Amino Acids & Nucleotides Dr. Kornberg: Lecture 04.26.17 (0:00-5:06) 5 min 1 Biosynthesis Amino Acids & Nucleotides How are Ribonucleic Acid Precursors So far: converted to Deoxyribonucleic Acid GMPàGDPàGTP Precursors? ….....and how is dTTP made? AMPàADPàATP 2’C-OH bond is directly reduced to 2’-H UMPàUDPàUTPà bond …without activating the carbon for CDPßCTP dehydration, etc.! catalyzed by ribonucleotide reductase Specific kinases, Non-specific kinase, e.g., UMP kinase, nucleoside GMP kinase, diphosphate kinase Very unique enzyme in all of biochemistry – use of free Adenylate kinase (works on both oxy- and radicals etc. deoxy-ribose GDPàdGDP nucleosides) Mechanism: Two H atoms are donated ADPàdADP by NADPH and carried by thioredoxin or glutaredoxin to the active site. UDPàdUDP –Substrates are the NDPs and the products CDPàdCDP are dNDP. Biosynthesis Amino Acids & Nucleotides Source of Reducing Structure of Ribonucleotide Reductase a2 are regulatory Electrons for and half the Ribonucleotide catalytic site; need to be reduced. Reductase b 2 are the other half (a b ) of the active site, 2 2 and the free- radical generators • NADPH serves as the electron donor. • Funneled through glutathione or JoAnne Stubbe thioredoxin pathways (1946– ) 2 •Most forms of enzyme have two catalytic/ regulatory subunits and two radical- generating subunits.
    [Show full text]
  • Metabolism Unit III Lipid Anabolism (MSLSC2001C04)
    Metabolism MSLSC2001C04 Course Instructor Dr. Gautam Kumar Dr. Gautam Kr. Dept. of Life Sc 1 Dr. Gautam Kr. Dept. of Life Sc 2 Lipids Metabolism • Lipids are the principal form of stored energy in most organisms and major constituents of cellular membranes. • Specialized lipids serve as pigments (retinal, carotene) cofactors (vitamin K), detergents (bile salts), transporters (dolichols), hormones (vitamin D derivatives, sex hormones), extracellular and intracellular messengers (eicosanoids, phosphatidylinositol derivatives), and anchors for membrane proteins (covalently attached fatty acids, prenyl groups, and phosphatidylinositol). • Water-insoluble products from water-soluble precursors such as Acetate. • During Fatty acids synthesis ATP as a source of metabolic energy and a reduced electron carrier (usually NADPH). Dr. Gautam Kr. Dept. of Life Sc 3 Lipid Metabolism • Fatty acid synthesis takes place in the compartment in which NADPH is available for reductive synthesis (i.e., where the [NADPH]/[NADP] ratio is high) Subcellular localization of lipid metabolism Dr. Gautam Kr. Dept. of Life Sc 4 Acetyl-CoA Shuttle • Shuttle for transfer of AcetylDr.- GautamCoA Kr.groups Dept. of Life from Sc mitochondria to the cytosol5 • The mitochondrial outer membrane is freely permeable to all these compounds. • Pyruvate derived from amino acid catabolism in the mitochondrial matrix, or from glucose by glycolysis in the cytosol, is converted to acetyl-CoA in the matrix. • Acetyl groups pass out of the mitochondrion as citrate; in the cytosol they are delivered as acetyl-CoA for fatty acid synthesis. • Oxaloacetate is reduced to malate, which returns to the mitochondrial matrix and is converted to oxaloacetate. • Cytosolic malate is oxidation by malic enzyme to generate cytosolic NADPH; the pyruvate produced returns to the mitochondrial matrix.
    [Show full text]
  • Insulin Resistance of Protein Anabolism Accompanies That of Glucose Metabolism in Lean, Glucose-Tolerant Offspring of Persons with Type 2 Diabetes
    BMJ Open Diab Res Care: first published as 10.1136/bmjdrc-2016-000312 on 29 November 2016. Downloaded from Open Access Research Insulin resistance of protein anabolism accompanies that of glucose metabolism in lean, glucose-tolerant offspring of persons with type 2 diabetes Sergio A Burgos,1,2 Vikram Chandurkar,3 Michael A Tsoukas,1 Stéphanie Chevalier,1 José A Morais,1 Marie Lamarche,1 Errol B Marliss1 To cite: Burgos SA, ABSTRACT Significance of this study Chandurkar V, Tsoukas MA, Objective: To test whether protein anabolic resistance et al . Insulin resistance of is an early defect in type 2 diabetes (T2D). protein anabolism What is already known about this subject? accompanies that of glucose Research design and methods: Seven lean, ▪ The offspring of patients with type 2 diabetes are metabolism in lean, glucose- normoglycemic T2D offspring (T2D-O) and eight at a higher risk of developing the disease. tolerant offspring of persons matched participants without family history (controls; ▪ 2 Previous studies have identified several abnor- with type 2 diabetes. BMJ C) underwent a 3-hour hyperinsulinemic (40 mU/m / malities in glucose and lipid metabolism in this Open Diabetes Research and min), euglycemic (5.5 mmol/L) and isoaminoacidemic population, but the status of protein metabolism Care 2016;4:e000312. clamp. Whole-body glucose and protein kinetics were 3 13 is not known. doi:10.1136/bmjdrc-2016- measured with D-[3– H]glucose and L-[l- C]leucine, 000312 respectively. Plasma amino acids were measured by What are the new findings? liquid chromatography-tandem mass spectrometry. ▪ The main finding of the study is the presence of Results: Fasting glycemia and glucose kinetic altered protein metabolism in lean young off- ▸ Additional material is variables did not differ between groups.
    [Show full text]