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Showing papers in "Annual Review of Biochemistry in 1977"


Journal ArticleDOI
TL;DR: The LDL Pathway is a Vehicle for Normal Human PhySIOLOGY and the PATHOGENESIS of ATHEROSCLEROSIS and its implications for normal human physiology and the pathogenesis of AtherOSCLerosis are discussed.
Abstract: PERSPECTIVES AND SUMMARY 898 LDL, THE MAJOR CHOLESTEROL-CARRYING LIPOPROTEIN OF HUMAN PLASMA . 901 Structure of Plasma LDL .. ... .... 901 Origin of Plasma LDL 902 Catabolism of Plasma LDL 902 THE LDL PATHWAY IN HUMAN FIBROBLASTS ..... ...... 903 The LDL Receptor 903 Endocytosis of Receptor-bound LDL .... 908 Lysosomal Hydrolysis of LDL-Protein and LDL-Cholesteryl Esters 910 Regulation of Cholesterol Synthesis and Cholesteryl Ester Formation .... .. 911 REGULATION OF THE LDL RECEPTOR . 912 MUTATIONS AFFECTING THE LDL PATHWAy 915 THE LDL PATHWAY IN CULTURED HUMAN LYMPHOID CELLS AND AORTIC SMOOTH MUSCLE CELLS ... . ..... ........ .... 918 THE LDL PATHWAY IN HUMAN CELLS IN VIVO 919 IMPLICATIONS OF THE LDL PATHWAY FOR NORMAL HUMAN PHYSIOLOGY AND THE PATHOGENESIS OF ATHEROSCLEROSIS ........ ....... 923

2,384 citations


Journal ArticleDOI
TL;DR: The Reactive Serine and the Charge Relay System are studied as well as polypeptide binding sites and the Tetrahedral Binding and the Oxyanion Binding Site are studied.
Abstract: PERSPECTIVES AND SUMMARY .... 331 THE REACTION SEQUENCE AND INTERMEDIATES .... . .. . ..... 333 TRANSITION-STATE STABILIZATION .... .. . . . ... .. . 338 STRUCTURAL FEATURES PARTICIPATING IN CATALYSIS ........ 341 Polypeptide Binding on the Acyl-Group Side 342 Side-Chain Specificity Sites 344 Polypeptide Binding on the Leaving-Group Side 346 Tetrahedral Binding and the Oxyanion Binding Site 348 The Reactive Serine and the Charge Relay System . . . . . . . . . . . . . . . . . . . . . . 351

1,228 citations


Journal ArticleDOI
TL;DR: This chapter discusses major advances in prostaglandin chemistry and biological activity and indicates the extent to which research has progressed towards the realization of earlier hopes of the discovery of new therapeutic agents.
Abstract: Publisher Summary This chapter discusses prostaglandins and thromboxanes. The prostaglandins are C 20 acids formed from polyunsaturated fatty acids by oxygenation and cyclization. The thromboxanes, which were originally found in platelets, have now been identified in a variety of tissues. Rapid progress is being made in understanding their biological roles. Earlier studies on vascular and airway smooth muscle demonstrated that endoperoxides had unique effects that could not be attributed to conversion into the stable prostaglandins. Because aspirin, an inhibitor of endoperoxide formation, inhibits the second wave of aggregation, it was suggested that the endoperoxides play a role in the release reaction. The potency of the endoperoxides in causing contractions of the isolated rabbit aorta was of particular interest. However, the occurrence of thromboxanes is not limited to platelets. The transformation of arachidonic acid into thromboxane B 2 has also been observed in lung tissue, spleen, kidney, leukocytes, umbilical artery, and brain.

1,223 citations


Journal ArticleDOI
TL;DR: The structure of nucleus and linker is described and the path followed by the DNA is described, revealing the arrangement of Histones and their role in theogenesis.
Abstract: STRUCTURE OF NUCLEOSOMES 940 Core and Linker 940 Arrangement of Histones 942 Path Followed by the DNA 944 Conformation of Histones 948

1,156 citations


Journal ArticleDOI
TL;DR: In this paper, a proper assay of fully activated Enzyme was performed and the relationship between Carboxylase and Oxygenase activity was investigated in the Chloroplast.
Abstract: INTRODUCTION 379 Role in Photosynthesis 379 Enzyme Reaction 380 MOLECULAR PROPERTIES .... . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . ... . . . .. 381 Native Enzyme 381 Subunit Structure 382 Is Bound Capper Involved? 384 CATALYTIC PROPERTIES .... . ..... 384 Identification of Enzyme Activation 384 Oxygenase Activity 388 Relationship Between Carboxylase and Oxygenase 389 Kinetics of the Activated Enzyme ........ 390 Proper Assay of Fully Activated Enzyme ... ..... . ... 393 SUMMARY OF KINETIC PARAMETERS ........ . . . ... . . . . ... 393 CONCLUSIONS ... .. . ....... .. . .. ..... . .. .. . .. .. . . . . . . .. . . .. ... ... . .. . . . . . . ... . .. . . . . .. . . ....... 394 Physiological Control of CO2 Fixation in the Chloroplast 394 Future Research Aspects 395

758 citations


Journal ArticleDOI
TL;DR: The ultimate goal is to correlate the biological properties of these peptides with their effects on the physical properties of membranes and to rationalize these events in terms of lipid-peptide interactions.
Abstract: The general mechanism for the antibiotic activities of the polymyxins and octapeptins has been elucidated by research using a broad range of experimental techniques. However, this phenomenon has not been described in detailed molecular terms, and this must be one of the major goals for future research in this area. Since 1947, when polymyxin was first isolated, there have been tremendous advances in our knowledge of membrane structure. The application of biophysical technology such as NMR, ESR, fluorescence spectroscopy, differential scanning calorimetry, and electron microscopy has been particularly valuable for studying model and biological membrane structures. It is these techniques which will provide a detailed molecular mechanism for the effects of these peptide antibiotics on membrane structure. In addition, the large number of antibiotic derivatives available should be exploited more extensively for structure-function correlations. The ultimate goal is to correlate the biological properties of these peptides with their effects on the physical properties of membranes and to rationalize these events in terms of lipid-peptide interactions.

724 citations



Journal ArticleDOI
TL;DR: This paper presents a meta-analyses of cyclic GMP-dependent protein kinase and its role in energy-providing catalysis, and its applications in regenerative medicine and cell reprograming.
Abstract: PERSPECTIVES AND SUMMARY 824 INTRODUCTION ...... 825 GUANYLATE CYCLASE 826 Occurrence ,'.... 827 Physical Characteristics 829 Kinetic Characteristics ,.... 830 Modulators " "... 833 Hormones , " 834 Lipids 834 Oxidation and reduction ... . 837 CYCLIC GMP PHOSPHODIESTERASE ........ . .. ....... . . . . ....... . . . . . . .. . . 840 Occurrence 841 Kinetic Characteristics 843 Modulators 843 General 843 Calcium-dependent regulator 844 A TP-dependent activator in retina 847 Retinal dystrophies 848 Possible utility as an energy-providing catalysis 849 CYCLIC GMP INTERACTIONS WITH CELLULAR COMPONENTS 851 Binding Components and Enzyme-Catalyzed Processes 852 CycliC GMP-dependent Protein Kinase 856 Modulator(s) of cyclic GMP-dependent protein kinase 859 Cyclic GMP-promoted endogenous phosphorylations of cellular proteins ........ 862

595 citations


Journal ArticleDOI
Osamu Hayaishi1, K Ueda1
TL;DR: This chapter analyzes poly(ADp-ribose) and ADP-ribosylation of proteins, a novel type of covalent modification of proteins that is implicated in the regulation of cell proliferation, protein synthesis, and DNA as well as RNA metabolism.
Abstract: Publisher Summary This chapter analyzes poly(ADP-ribose) and ADP-ribosylation of proteins. Poly(ADP-ribose) and the ADP-ribosylation of proteins constitute a novel type of covalent modification of proteins. They are ubiquitously distributed in nature and are implicated in the regulation of cell proliferation, protein synthesis, and DNA as well as RNA metabolism. This type of post-translational modification is unique because NAD, nicotinamide adenine dinucleotide, whose primary function is an electron carrier in biological oxidation, invariably provides the ADP-ribosyl moiety, which is transferred on to a protein molecule. The ADP-ribosyl unit thus, covalently attached to a protein acceptor is present as either a monomer or a polymer as in the case of the nuclear system. This chapter also summarizes developments in this field of research and some experimental results. It reviews briefly, mono ADP-ribosylation of proteins, in which only a single ADP-ribosyl moiety is transferred to a protein acceptor. It also covers a more complex reaction, poly(ADP-ribose) in nuclei, in which the ADP-ribosyl units are polymerized.

581 citations


Journal ArticleDOI
TL;DR: The obtained results allowed us to assess the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals, not necessarily belonging to the same breeds.
Abstract: INTRODUCTION AND PERSPECTIVE ....... 524 THE PROCEDURE AND THE PROBLEMS. . . . . .... ...... . . .. . ... . . .... .... . 525 CHEMISTRY OF SELECTED REAGENTS 527 Alkyl Imidates (lmidoesters} 527 Synthesis 528 Reaction paths and mechanisms 528 Use as modifYing reagents 531 Acyl Azides 532 Sulfhydryl Reagents 532 Nitrenes 534 Glutaraldehyde 537 Cross-linking Reversal-Cleavable Reagents 539 APPLICATIONS IN A FEW SELECTED SYSTEMS 540 Ribosomes ,. 540 Histones 542 Red Cells 542 Mitochondria 545 Escherichia coli .... ... ..... ....... ..... ....... .... ... ...... ...... ....... .... ... ... ......... ..... ... ..... ... 545 Sarcoplasmic Reticulum 546 Other Preparations 547 PROGNOSIS 549

573 citations


Journal ArticleDOI
TL;DR: This poster discusses the phytochemical properties of actin and myosin, and some of the properties of these properties have been reported to be attractive to the immune system and promote wound healing.
Abstract: PERSPECTIVES AND SUMMARY ..... 797 INTRODUCTION ....... 799 PROPERTIES OF ACTIN AND MYOSIN . 800 Actin 800 Myosin . 802


Journal ArticleDOI
TL;DR: The structure of the Membrane and its components, including the respiratory chain, ATPase, and related energy-transducing systems, are studied in detail.
Abstract: PERSPECTIVES AND SUMMARY 202 INTRODUCTION 203 Contemporary Concepts of Membrane Structure 204 Methodology for Studying the Topology of Membranes ... ........ 205 Enzyme topology in the lateral plane ...... 205 Enzyme topology in the transverse plane ........ 206 Lipid topology .... ..... ....... ...... ........ 206 Other methods ......... ......... ....... ... ... ... ..... ... 207 MITOCHONDRIA 207 Morphology 207 The Outer Membrane ......... 207 The Inner Membrane 209 General features ...... ...... ... ...... ... ..... ..... ........ 209 General aspects of lateral topology ...... ........ ...... 210 General aspects of transverse topology ........ ........ ........ 212 The respiratory chain, ATPase, and related energy-transducing systems 214 General features 214 NADH-Q reductase (Camp/ex I) 215 Succinate-Q reductase (Complex II) 217 Ubiquinone ... ..... ....... ...... ..... 218 QHrcytochrome c reductase (Complex III) .... 220 Cytochrome c .... ..... ....... ....... ...... 221 Cytochrome c oxidase (Comp/ex IV) 222 Transhydrogenase .. ..... ..... ..... .... ... ......... ... ... ....... ... ... ........ .... 226 ATPase 227 Ion trans/ocators ... ... ... ........ ... ... ..... 229 Other enzymes . ........ ..... ... ......... ... ... ... ...... .... 230

Journal ArticleDOI
TL;DR: An attempt is made to evaluate the phytochemical properties of the fruit extract of citric acid and its application in the treatment of neurological disorders.
Abstract: PERSPECTIVES AND SUMMARy 157 INACTIVE PLASMA PROTHROMBIN INDUCED BY COUMARIN: ANTICOAGULANTS 159 CHARACTERIZATION OF y-CARBOXYGLUTAMIC ACID 162 FUNCTIONAL SIGNIFICANCE OF THE VITAMIN K-DEPENDENT CARBOXYLATIONS 164 HEPATIC PRECURSORS OF PROTHROMBIN 165 VITAMIN K-DEPENDENT CARBOXYLATION 166 y-CARBOXYGLUTAMIC ACID IN OTHER TISSUES 168 VITAMIN K EPOXIDE 168 CONCLUDING REMARKS 169

Journal ArticleDOI
TL;DR: The present study focuses on the development of a novel and scalable approaches to integrate mitochondria into the food chain through a number of simple and efficient mechanisms.
Abstract: PERSPECTIVES AND SUMMARY ................ ................... .... ... ....................... ....... ... . 264 CHEMICAL MECHANISM OF FATTY ACID SYNTHESIS ........... ...... ........ . ..... . 266 Primer Studies ........................................................................................................ 266 ACETYL-CoA CARBOXYLASE (IN VITRO) .............. ............ ... ............................. 267 Escherichia coli ...................................................................................................... 267 Eukaryotes................................................................................................................ 268 FATTY ACID SYNTHETASES (TYPE II) ........................................ .......... .............. 270 SUBUNIT STRUCTURE OF FATTY ACID SYNTHETASES (TYPE I) ......... .. ... 272 FATTY ACID SYNTHETASE OF MYCOBACTERIUM SMEGMATIS .............. 277 MEMBRANE-ASSOCIATED ELONGATION SySTEMS........................................ 280 Microsomal Systems .............................................................................................. 280 Mitochondrial Systems ............................ ..................................................... ......... 281


Journal ArticleDOI
TL;DR: A comparison study of DNA Polymerase Activities and DNA Synthesis in Vivo and Template Studies reveals a lack of interrelationship between the Enzymes and Polymerases.
Abstract: PERSPECTIVES A ND SU MMARY ......... 25 IN TR ODUCTION ........ ... 27 CE LLU LAR DNA POL YMERASES ....... . 28 DNA Polymerase a ......... 28 DNA Polymerase /3 31 DNA Polymerase 'Y •.....• • 33 Mitochondrial DNA Polymerase .... ......... 34 VIR US-INDUCED DNA POL YMERASES ......... .... 35 DNA Polymerases Induced by Herpesvirus 35 DNA Polymerase Activities of Parvoviruses and the Hepatitis B Particle.. 36 Changes Induced by Papovavirus and Adenovirus Infection 37 COMPARA TIVE STUDIES OF THE DNA POLYMERASES 37 Lack of Interrelationship of the Enzymes 37 DNA Polymerase Activities and DNA Synthesis in Vivo 39 DNA Polymerases during Development 41 Template Studies 42 Other DNA Polymerases 43 CONCLUSION 43

Journal ArticleDOI
TL;DR: A Hypothetical Model for a Protein Electron-Transfer Complex and Implications for Oxidoreduction Mechanisms in Cytochromes are presented.
Abstract: PERSPECTIVES AND SUMMARY .. ...... ...... .... ... ... ... ... ... ... .. ... .. ....... .. .. ... .... 299 OCCURRENCE AND STRUCTURAL FEATURES OF HIGH-POTENTIAL CYTOCHROMES C 302 OXIDATION-REDUCTION MECHANISMS 310 General Considerations 310 Proposals for Oxidoreduction Mechanisms in Cytochromes c 314 INTERACTIONS WITH PHYSIOLOGICAL OXIDOREDUCTASES 31B Comparative Structural Studies .... .... .... ..... .... ... ... .... ... ... .... .. ... ... .. .. ... ... ... ..... .. ... .. 31B A Hypothetical Model for a Protein Electron-Transfer Complex .. ..... .. .... .. . 319 OXIDATION STATE-COUPLED STRUCTURAL CHANGES 324 CONCLUDING REMARKS . ..... ... .... ..... ... ... .. ..... .. ... .... ......... ....... ... ........ ..... ..... 326

Journal ArticleDOI
TL;DR: A Comparative Study of Coupling Hypotheses for Chemiosmotic versus Nonosmotic Reaction Mechanisms and the Foundations of Stoichiometry, Thermodynamics, and Kinetics.
Abstract: RESEARCH STRATEGY: A CALCULATED GAME OF CHANCE 996 Coupling Hypotheses: Chemiosmotic versus Nonosmotic 996 Chemiosmotic Reaction Mechanisms: Direct and Indirect .... ..... .... .... .... ..... 999 PROTON MOTIVE CHEMIOSMOTIC SYSTEMS .... 1000 Reversible Proton motive ATPase ... 1000 Proton motive Cytochrome Systems and Q Cycles 1001 Protonmotive NADH Dehydrogenase and NAD(P) Transhydrogenase ...... 1002 Bacterial Proton motive Cytochrome Systems, Photoredox Systems, and Redox Loops 1002 Stoichiometry, Thermodynamics, and Kinetics 0/ Coupled Systems .... ...... 1002 SOLUTE PORTER SySTEMS 1003 CONCLUSION 1004


Journal ArticleDOI
TL;DR: This paper presents a meta-analysis of SV40 and Polyoma viruses using a probabilistic approach to estimate the number of replication events and the importance of these events to the structure of the virus itself.
Abstract: PERSPECTIVES AND SUMMARY 472 POLYOMA VIRUSES 475 PROTEINS OF POLYOMA VIRUS AND SV40 476 GENOMES OF PAPOVAVIRUSES 477 Properties of SV40 and Polyoma DNAs 477 Physical Mapping of SV40 and Polyoma DNAs 481 Comparison of Virus Strains 481 REPLICATION OF SV40 AND POLYOMA DNAs 482 Initiation 483 Polynucleotide Chain Propagation and Unwinding of Template Strands.. 484 Termination 484 VIRAL NUCLEOPROTEIN COMPLEXES 485 TRANSCRIPTION OF SV40 AND POLyOMA 485 Early Transcription 486 Late Transcription 486 Comparison of SV40 and Polyoma 487 HUMAN PAPOVAVIRUSES 489 DAR Virus 490 JC and BK Viruses 490

Journal ArticleDOI
TL;DR: This paper presents a meta-analyses of humoral Immunity (Antibody Formation) and Cell-Mediated Immunity (Delayed Hypersensitivity Reactions) and its applications in Lysis and Liposomes with Multiple Determinants.
Abstract: PERSPECTIVES AND SUMMARY 49 EFFERENT RESPONSES 50 Humoral (Complement-Mediated) Lysis 50 Classical pathway 50 Alternative pathway; reactive lysis 54 Mechanism 55 Electron microscopic observations; hole formation 57 Additional applications 59 Cell-Mediated Lysis 60 AFFERENT RESPONSES 60 Humoral Immunity (Antibody Formation) 61 Cell-Mediated Immunity (Delayed Hypersensitivity Reactions) 62 Liposomes with Multiple Determinants 63


Journal ArticleDOI
TL;DR: This paper presents a meta-anatomy of the web of elements that makes up the internet, and some of the elements that make up the web are substances such as carbon dioxide, nitrogen, and phosphorous.
Abstract: NATURE AND SCOPE 967 THE RESPIRATORY CHAIN ... . . . . .. . .. . ... ......... . ........ . . . ..... .. 968 ENERGY-COUPLING COMPONENTS 970 COUPLING OF ELECTRON FLOW TO ION TRANSPORT 973 MEMBRANE POTENTIALS 975 CONTROL OF ELECTRON FLOW 976


Journal ArticleDOI
TL;DR: The results show that proton Uptake and Proton Gradients are higher in the presence of ATP than in the absence of ATP, and the total number of proton-proton collisions in the H2O–O2 mixture is higher than the other ways around.
Abstract: PERSPECTIVES AND SUMMARy 143 ENERGY CONSERVATION ALONG THE ELECTRON-TRANSPORT PATH 144 ATP to Electron Ratios 144 Electron Donors, Acceptors, and Inhibitors 145 THE HIGH ENERGY STATE 146 Postillumination and Acid-Base ATP Synthesis 146 Proton Uptake and Proton Gradients 147 Membrane Potentials 148 Energy-Dependent Reverse Reactions ... 149 Exchange Reactions 150 THE ATP-SYNTHESIZING COMPLEX 151 The Coupling Factor ........ ...... 151 Nucleotide Interactions 152

Journal ArticleDOI
TL;DR: The results obtained allowed us to assess the importance of knowing the carrier and removal status of the gas molecule as a source of energy and their applications in the context of an integrated energy system.
Abstract: INTRODUCTION 981 SOME BASIC CONCEPTS AND QUESTIONS 982 MECHANISMS OF PROTON TRANSLOCATION BY ENERGY-TRANSDUCING UNITS ... . . . . . . . ...... . . . . . . . . ....... . . . . . 984 ENERGIZED CONFORMATIONAL STATES . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . .. . . . . . . . . ... 988 ENERGY-TRANSFER DOMAINS 990 CONCLUSIONS 992

Journal ArticleDOI
TL;DR: A holistic view of RECEPTOR-MEDIATED ELECTRICAL CHANGES is presented, which considers the role of receptors, ligand Binding and Receptor Functioning, and theoretical models.
Abstract: PERSPECTIVES AND SUMMARY 117 ELECTROPHYSIOLOGICAL PR PERTIES 119 Time Constants and Noise Analysis 119 Gating Concept 120 GATING THEORIES 121 Cooperativity 121 Theoretical Models. 122 CHEMICAL G TING PROCESSES 123 THE ACETYLCHOLINE RECEPTOR SYSTEM 125 Heterogeneity of Receptor Properties 127 Ligand Binding and Receptor Functioning 131 Structural Organization and Functional Role of Receptor Subunits 134 AN INTEGRAL VIEW OF RECEPTOR-MEDIATED ELECTRICAL CHANGES 136

Journal ArticleDOI
TL;DR: The invitation of the Editorial Committee to write a prefatory chapter deeply affirms the author's long commitment to biochemistry and she feels honored to be the first woman, the first in a long succession, to be chosen.
Abstract: The invitation of the Editorial Committee to write a prefatory chapter deeply affirms my long commitment to biochemistry. I feel honored to be the first woman, I trust the first in a long succession, to be so chosen. My preoccupations with the intermediary metabolism of amino acids and proteins began in 1937 when research laboratories in this country were occupied with the chemistry of amino acids and with nutritional studies. Major contributions were being made on the functional role of vitamins in nutrition and in elucidation of the chemical structure of vitamins. In the field of sterols, activity was reflected in major contributions to the nature of vitamin D and to the structure and action of the estrogenic hormones. Not until I became thoroughly immersed in research on amino acid metabolism did I catch up with the biochemical developments in European and English laboratories emerging from the elucidation of the function of vitamins as cofactors in enzymatic catalysis, thus stimulating and making poss...