Biochemistry: Catabolism of Carbohydrates
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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. -
The Citric Acid Cycle the Catabolism of Acetyl-Coa
Al-Sham Private University Faculty Of Pharmacy The Citric Acid Cycle The Catabolism of Acetyl-CoA Lecturer Prof. Abboud Al-Saleh 1 Prof.Abboud AL-Saleh 10/1/2018 BIOMEDICAL IMPORTANCE • The citric acid cycle (Krebs cycle, tricarboxylic acid cycle) is a series of reactions in mitochondria that oxidize acetyl residues (as acetyl-CoA) and reduce coenzymes that upon reoxidation are linked to the formation of ATP. • TCA is the final common pathway for the aerobic oxidation of carbohydrate, lipid, and protein because glucose, fatty acids, and most amino acids are metabolized to acetyl-CoA or intermediates of the cycle. 2 Prof.Abboud AL-Saleh 10/1/2018 • TCA also has a central role in gluconeogenesis, lipogenesis, and interconversion of amino acids. Many of these processes occur in most tissues, but the liver is the only tissue in which all occur to a significant extent. • The repercussions are therefore profound when, for example, large numbers of hepatic cells are damaged as in acute hepatitis or as in cirrhosis. • Very few, if any, genetic abnormalities of TCA enzymes have been reported; such abnormalities would be incompatible with life or normal development 3 Prof.Abboud AL-Saleh 10/1/2018 Summary • The cycle starts with reaction between the acetyl moiety of acetyl-CoA and the four-carbon dicarboxylic acid oxaloacetate, forming a six-carbon tricarboxylic acid, citrate. • In the subsequent reactions, two molecules of CO2 are released and oxaloacetate is regenerated (Figure). • Only a small quantity of oxaloacetate is needed for the oxidation of a large quantity of acetyl-CoA. • oxaloacetate may be considered to play a catalytic role. -
Catabolism Iii
Nitrogen Catabolism Glycogenolysis Protein Fat catabolism Catabolism Fatty Acid Amino-acid GlycolysisDegradation catabolism Pyruvate Oxidation Krebs' Cycle Phosphorylation Oxidative CATABOLISM III: Digestion and Utilization of Proteins • Protein degradation • Protein turnover – The ubiquitin pathway – Protein turnover is tightly regulated • Elimination of nitrogen – By fish, flesh and fowl – How is the N of amino acids liberated and eliminated? • How are amino acids oxidized for energy 1 Protein Catabolism Sources of AMINO ACIDS: •Dietary amino acids that exceed body’s protein synthesis needs •Excess amino acids from protein turnover (e.g., proteolysis and regeneration of proteins) •Proteins in the body can be broken down (muscle wasting) to supply amino acids for energy when carbohydrates are scarce (starvation, diabetes mellitus). •Carnivores use amino acids for energy more than herbivores, plants, and most microorganisms Protein Catabolism The Digestion Pathway • Pro-enzymes are secreted (zymogens) and the environment activates them by specific proteolysis. • Pepsin hydrolyzes protein into peptides in the stomach. • Trypsin and chymotrypsin hydrolyze proteins and larger peptides into smaller peptides in the small intestine. • Aminopeptidase and carboxypeptidases A and B degrade peptides into amino acids in the small intestine. 2 Protein Catabolism The Lysosomal Pathway • Endocytosis, either receptor-mediated, phagocytosis, or pinocytosis engulfs extra- cellular proteins into vesicles. • These internal vesicles fuse as an early endosome. • This early endosome is acidified by the KFERQ Substrates vATPase (“v” for vesicular). • Components that are recycled, like receptors, HSPA8 are sequestered in smaller vesicles to create Co-chaperones the multivesicular body (MVB), sometimes called a late endosome. • If set for degradation, it will fuse with a KFERQ primary lysosome (red) which contains many cathepsin-type proteases. -
The Metabolism of Subcutaneous Adipose Tissue in the Immediate Postnatal Period of Human Newborns
Pediat. Res. 6: 211-218 (1972) Adipose tissue glucose metabolism /3-hydroxyacyl-CoA dehydrogenase neonates fatty acid catabolism phosphofructokinase The Metabolism of Subcutaneous Adipose Tissue in the Immediate Postnatal Period of Human Newborns. 2. Developmental Changes in the Metabolism of 14C-(U)-D-Glucose and in Enzyme Activities of Phosphofructo- kinase (PFK; EC. 2.7.1.11) and /3-Hydroxyacyl-CoA Dehydro- genase (HAD; EC. 1.1.1.35) M. NOVAK1351, E. MONKUS, H. WOLF, AND U. STAVE Department of Pediatrics, University of Miami School of Medicine, Miami, Florida, USA, Staedtische Kinderklinik, Kassel, West Germany, and Fels Research Institute, Yellow Springs, Ohio, USA Extract Changes in the in vitro metabolism of subcutaneous adipose tissue have been compared in normal human newborns from 2 hr to 2 weeks of age. A group of healthy adult volunteers was also included. Samples were obtained by using a needle biopsy tech- nique. More of the isotope from uC-(U)-D-glucose was incorporated into triglyc- erides (P < 0.05) and also oxidized by suspensions of adipose cells from infants 2-3 hr of age than in older infants (P < 0.01). The ratio of radioactivity in carbon dioxide to radioactivity in triglyceride was also significantly greater in 2- to 3-hr-old infants than in older neonates (P < 0.05). Thin layer chromatography of the total lipid ex- tract showed the greatest amount of radioactivity in the triglycerides, a small amount in 1,3-digiycerides and 1,2-diglycerides, and a trace in fatty acids and monogiyc- erides. These findings were compared with the developmental changes in two key enzymes: phosphofructokinase (PFK), which represents the glycolytic pathway, and (3-hydroxyacyl-coenzyme A (GoA) dehydrogenase (HAD), which is involved in the P oxidation of fatty acids. -
Chapter 12 Slides
11/15/17 CHAPTER 12: Carbohydrates: Structure and Function OUTLINE • 12.1 Role of Carbohydrates • 12.2 Monosaccharides • 12.3 Complex Carbohydrates • 12.4 Carbohydrate Catabolism • 12.5 Oligosaccharides as Cell Markers CHAPTER 12: Carbohydrates: Structure and Function WHAT ARE CARBOHYDRATES? • Glucose and its derivatives are carbohydrates: Ø Carbohydrates are simple organic molecules that have a shared basic chemical Formula: Cn(H2O)n Ø The name “carbo + hydrate” represents that Fact that they are made from CO2 and H2O by photosynthesis • About halF oF all earth’s solid carbon is Found in two polymers of glucose found in plants: Ø Starch = major energy storage molecule Ø Cellulose = major structural component oF the plant cell wall (aka. “fiber”) CHAPTER 12: Carbohydrates: Structure and Function THE SIMPLEST CARBOHYDRATES • Monosaccharides are carbohydrates that cannot be hydrolyZed into simpler carbohydrates: Ø These are the Fundamental building blocks For all other carbohydrates (oFten called “simple sugars”) Ø All have Formulas of based on the basic pattern: Cn(H2O)n • Monosaccharides have speciFic Functional groups: 1. An aldehyde OR a ketone (not both!) 2. Several (two or more) alcohol (-OH) groups 1 11/15/17 CHAPTER 12: Carbohydrates: Structure and Function STRUCTURE & NOMENCLATURE OF MONOSACCHARIDES • Monosaccharides are classiFied by two features: 1. Length of their main carbon chain (utilize standard IUPAC naming For # oF carbons) 2. Whether they contain an aldehyde or ketone group • Names always end with –ose • Two common hexoses: -
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 -
Aerobic and Nitrate Respiration Routes of Carbohydrate Catabolism in Pseudomonas S Tut Zeri
AN ABSTRACT OF THE THESIS OF WILLIAM JAN SPANGLER for the Ph. D. in MICROBIOLOGY (Name) (Degree) (Major) thesis is presented Date 7 / `> /q6! Title AEROBIC AND NITRATE RESPIRATION ROUTES OF CAR- BOHYDRATE CATABOLISM IN PSEUDOMONAS STUTZERI Abstract approved ( Major professor) Pseudomonas stutzeri and other denitrifying bacteria are able to grow under anaerobic conditions, using nitrate -oxygen as the terminal hydrogen acceptor, in a manner analagous to classical aerobic respiration with free -molecular oxygen. This rather unique phenomenon is known as nitrate respiration. Nitrate respiration has been studied with respect to the nitrate reducing enzymes and carrier systems involved in the reduction sequence, but very little emphasis has been placed on the metabolic pathways which are associated with nitrate respiration. This study was carried out in an attempt to establish the metabolic pathways operative, both under aerobic con- ditions and during nitrate respiration, in order to determine whether there was any shift of pathways under conditions of nitrate respira- tion. Primary pathways were determined by the radiorespirometric method using specifically labelled glucose and gluconate. The results, based primarily on the rate of decarboxylation of the C -1 and C -4 positions of glucose, indicated the operation of the Entner- Doudoroff and pentose phosphate pathways under both aerobic condi- tions and conditions of nitrate respiration. Evolution of 14CO2 from the other labels of glucose, as well as incorporation of these labels into the cell, indicated that terminal pathways such as the tricar- boxylic acid cycle or glyoxalate cycle might also be operative under both conditions of oxygen relationship. The secondary pathways were studied using specifically labelled acetate. -
Specific Catabolic Pathways
Chemistry 1506 Dr. Hunter’s Class Section 12 Notes - Page 1 Chemistry 1506: Allied Health Chemistry 2 Section 12: Specific Catabolic Pathways Molecular Destruction Outline SECTION 12.1 GENERAL FLOW OF CATABOLIC PATHWAYS..............................................................2 SECTION 12.2 GLYCOLYSIS ............................................................................................................................6 SECTION 12.3 TRIGLYCERIDE METABOLISM ..........................................................................................7 2000-2002, Dr. Allen D. Hunter, Department of Chemistry, Youngstown State University Chemistry 1506 Dr. Hunter’s Class Section 12 Notes - Page 2 Section 12.1 General Flow of Catabolic Pathways Overall Process Start with complex mixtures of food molecules Used to generate energy (as “fuel” molecules) ATP NADH and FADH2 Acetyl CoA Ultimate products are CO2, H2O, Urea (C(O)(NH2)2), etc. Intermediate Breakdown products may be used in Anabolic pathways 2000-2002, Dr. Allen D. Hunter, Department of Chemistry, Youngstown State University Chemistry 1506 Dr. Hunter’s Class Section 12 Notes - Page 3 Carbohydrate Catabolism 1st stages can start in the digestive tract Final stage is called glycolysis and finishes within the mitochondrion Polysaccharides ⇓ Oligosaccharides ⇓ Disaccharides ⇓ Monosaccharides ⇓ CO2 + “fuel” molecules 2000-2002, Dr. Allen D. Hunter, Department of Chemistry, Youngstown State University Chemistry 1506 Dr. Hunter’s Class Section 12 Notes - Page 4 Lipid Catabolism Starts in digestive system and ends inside mitochondria Lipases break the ester linkages in the triglycerides Triglycerides ⇓ Glycerol + Fatty Acids ⇓ ⇓ CO2 + “fuel” molecules 2000-2002, Dr. Allen D. Hunter, Department of Chemistry, Youngstown State University Chemistry 1506 Dr. Hunter’s Class Section 12 Notes - Page 5 Protein Catabolism Starts in digestive system and ends inside mitochondria Proteins ⇓ Peptides ⇓ Amino Acids ⇓ CO2 + “fuel” molecules + Urea 2000-2002, Dr. -
Nutritional Determinants of Metabolic Diseases in Humans
Unicentre CH-1015 Lausanne http://serval.unil.ch Year : 2019 NUTRITIONAL DETERMINANTS OF METABOLIC DISEASES IN HUMANS Surowska Anna Surowska Anna, 2019, NUTRITIONAL DETERMINANTS OF METABOLIC DISEASES IN HUMANS Originally published at : Thesis, University of Lausanne Posted at the University of Lausanne Open Archive http://serval.unil.ch Document URN : urn:nbn:ch:serval-BIB_635D730749F67 Droits d’auteur L'Université de Lausanne attire expressément l'attention des utilisateurs sur le fait que tous les documents publiés dans l'Archive SERVAL sont protégés par le droit d'auteur, conformément à la loi fédérale sur le droit d'auteur et les droits voisins (LDA). A ce titre, il est indispensable d'obtenir le consentement préalable de l'auteur et/ou de l’éditeur avant toute utilisation d'une oeuvre ou d'une partie d'une oeuvre ne relevant pas d'une utilisation à des fins personnelles au sens de la LDA (art. 19, al. 1 lettre a). A défaut, tout contrevenant s'expose aux sanctions prévues par cette loi. Nous déclinons toute responsabilité en la matière. Copyright The University of Lausanne expressly draws the attention of users to the fact that all documents published in the SERVAL Archive are protected by copyright in accordance with federal law on copyright and similar rights (LDA). Accordingly it is indispensable to obtain prior consent from the author and/or publisher before any use of a work or part of a work for purposes other than personal use within the meaning of LDA (art. 19, para. 1 letter a). Failure to do so will expose offenders to the sanctions laid down by this law. -
Energy Production in a Cell (Chapter 25 Metabolism)
Energy Production In A Cell (Chapter 25 Metabolism) Large food molecules contain a lot of potential energy in the form of chemical bonds but it requires a lot of work to liberate the energy. Cells need a quick easy way to get energy for anabolism: this is done with ATP. ATP is an unstable molecule, the bonds of which are easy to break making it a useful source of energy for cells. ATP → ADP + P + free energy from food Food energy + ADP + P → ATP Catabolic reactions generate energy to make ATP, and the ATP energy is used to drive anabolic reactions, such as metabolic turnover (replacement of cell parts), growth and cell division, and special functions (such as secretion, absorption, contraction, or signaling). Metabolism = the sum of all chemical reactions in the body; catabolism + anabolism All energy production begins in the cytosol of the cell. Large molecules are catabolized into smaller molecules, but very little energy is produced: Proteins → amino acids Triglycerides → fatty acids and glycerol Carbohydrates → short carbon chains These smaller molecules are then absorbed and processed in reactions inside the mitochondria. 40% of the energy is captured to produce ATP from ADP and the remaining 60% escapes as heat (used to maintain body temperature). Oxidation-Reduction Reactions (Redox Rxns) Oxidation = the removal of electrons (or addition of oxygen) Reduction = the addition of electrons These reactions are always coupled: one molecule must be oxidized while another is reduced. A-e’ + B → A + B-e’ (A is oxidized while B is reduced) The reduced molecule gains energy while the oxidized molecule loses energy. -
Amino Acid Catabolism: Urea Cycle the Urea Bi-Cycle Two Issues
BI/CH 422/622 OUTLINE: OUTLINE: Protein Degradation (Catabolism) Digestion Amino-Acid Degradation Inside of cells Urea Cycle – dealing with the nitrogen Protein turnover Ubiquitin Feeding the Urea Cycle Activation-E1 Glucose-Alanine Cycle Conjugation-E2 Free Ammonia Ligation-E3 Proteosome Glutamine Amino-Acid Degradation Glutamate dehydrogenase Ammonia Overall energetics free Dealing with the carbon transamination-mechanism to know Seven Families Urea Cycle – dealing with the nitrogen 1. ADENQ 5 Steps 2. RPH Carbamoyl-phosphate synthetase oxidase Ornithine transcarbamylase one-carbon metabolism Arginino-succinate synthetase THF Arginino-succinase SAM Arginase 3. GSC Energetics PLP uses Urea Bi-cycle 4. MT – one carbon metabolism 5. FY – oxidases Amino Acid Catabolism: Urea Cycle The Urea Bi-Cycle Two issues: 1) What to do with the fumarate? 2) What are the sources of the free ammonia? a-ketoglutarate a-amino acid Aspartate transaminase transaminase a-keto acid Glutamate 1 Amino Acid Catabolism: Urea Cycle The Glucose-Alanine Cycle • Vigorously working muscles operate nearly anaerobically and rely on glycolysis for energy. a-Keto acids • Glycolysis yields pyruvate. – If not eliminated (converted to acetyl- CoA), lactic acid will build up. • If amino acids have become a fuel source, this lactate is converted back to pyruvate, then converted to alanine for transport into the liver. Excess Glutamate is Metabolized in the Mitochondria of Hepatocytes Amino Acid Catabolism: Urea Cycle Excess glutamine is processed in the intestines, kidneys, and liver. (deaminating) (N,Q,H,S,T,G,M,W) OAA à Asp Glutamine Synthetase This costs another ATP, bringing it closer to 5 (N,Q,H,S,T,G,M,W) 29 N 2 Amino Acid Catabolism: Urea Cycle Excess glutamine is processed in the intestines, kidneys, and liver. -
Lecture 9: Citric Acid Cycle/Fatty Acid Catabolism
Metabolism Lecture 9 — CITRIC ACID CYCLE/FATTY ACID CATABOLISM — Restricted for students enrolled in MCB102, UC Berkeley, Spring 2008 ONLY Bryan Krantz: University of California, Berkeley MCB 102, Spring 2008, Metabolism Lecture 9 Reading: Ch. 16 & 17 of Principles of Biochemistry, “The Citric Acid Cycle” & “Fatty Acid Catabolism.” Symmetric Citrate. The left and right half are the same, having mirror image acetyl groups (-CH2COOH). Radio-label Experiment. The Krebs Cycle was tested by 14C radio- labeling experiments. In 1941, 14C-Acetyl-CoA was used with normal oxaloacetate, labeling only the right side of drawing. But none of the label was released as CO2. Always the left carboxyl group is instead released as CO2, i.e., that from oxaloacetate. This was interpreted as proof that citrate is not in the 14 cycle at all the labels would have been scrambled, and half of the CO2 would have been C. Prochiral Citrate. In a two-minute thought experiment, Alexander Ogston in 1948 (Nature, 162: 963) argued that citrate has the potential to be treated as chiral. In chemistry, prochiral molecules can be converted from achiral to chiral in a single step. The trick is an asymmetric enzyme surface (i.e. aconitase) can act on citrate as through it were chiral. As a consequence the left and right acetyl groups are not treated equivalently. “On the contrary, it is possible that an asymmetric enzyme which attacks a symmetrical compound can distinguish between its identical groups.” Metabolism Lecture 9 — CITRIC ACID CYCLE/FATTY ACID CATABOLISM — Restricted for students enrolled in MCB102, UC Berkeley, Spring 2008 ONLY [STEP 4] α-Keto Glutarate Dehydrogenase.