Showing papers in "Annual Review of Biochemistry in 1976"

Biological Applications of Ionophores

Abstract: FEATURES ..... 504 CLASSIFICATION OF lONOPHORES BY TRANSPORT MODES 506 Neutral Ionophores 506 Carboxylic Ionophores 506 Channel-Forming Quasi-Ionophores 508

1,4-Diaminobutane (Putrescine), Spermidine, and Spermine

Abstract: As is evident from the above summary of the recent literature, plus many other papers not cited here, there is an extensive literature indicating the physiological significance of these amines. The most important studies can be summarized as follows. (a) Polyamines and their biosynthetic enzymes are ubiquitous. (b) Microbiological mutants have been described in which there is a definite requirement of polyamines for growth. (c) The concentration of polyamines and their biosynthesis enzymes increase when the growth rate increases. These increases usually precede or are simultaneous with increases in RNA, DNA, and protein levels. (d) Ornithine decarboxylase has a remarkably fast turnover rate in animal cells, and the level of this enzyme rapidly changes after a variety of growth stimuli. (e) Polyamines have a high affinity for nucleic acids and stabilize their secondary structure. They are found associated with DNA in bacteriophages and have a variety of stimulatory effects on DNA and RNA biosynthesis in vitro. (f) Polyamines stimulate protein synthesis in vivo and in vitro. (g) Polyamines protect spheroplasts and halophilic organisms for lysis, indicating their ability to stabilize membranes. Despite these observations, no specific mechanism has been firmly established for the action of the polyamines in vivo. It is clear that these compounds are physiologically important, however, and further work is necessary to establish the mechanism of their action.

Comparative Aspects of Glycoprotein Structure

Abstract: Glycoproteins have a wide distribution in nature and serve a vast number of functions. There are glycoprotein enzymes and hormones; glycoproteins are found in blood and secretions, in cell membranes, and in connective tissue. Of all the biologically occurring macromolecules the glycoproteins, which consist of carbohydrate moieties convalently linked to a polypeptide backbone, represent the most diverse group, ranging from substances in which the carbohydrate component represents less than 1% of the total weight to those in which it represents over 80% of the total. The proteoglycans, which are classified separately from other glycoproteins and include the chondroitin sulfates, dermatan sulfates, and heparin primarily carbohydrate in the form of numerous heteropolysaccharide chains attached to a polypeptide chain at closely spaced intervals. The sugars that commonly occur in glycoproteins include galactose, mannose, glucose. N-acetylglucosamine, N-acetylgalactosamine, sialic acids, fucose, and xylose. The proteoglycans also contain various uronic and sulfated amino sugars.

The role of polyprenol-linked sugars in glycoprotein synthesis.

Abstract: PERSPECTIVES AND SUMMARY .... 95 MONOSACCHARIDE DERIVATIVES OF DOLICHOL .... ........ ..... ..... ......... 97 Biosynthesis and Structure 97 Other Lipid-Linked Monosaccharides 102 OLIGOSACCHARIDE-LIPIDS 103 Glucose-Containing Oligosaccharide-Lipids 103 Mannose-Containing Oligosaccharide-Lipids "'''''''''''''''''''''''''''''''''''''''''''''''''''''''''' 104

Steroid Receptors: Elements for Modulation of Eukaryotic Transcription

Abstract: PROKARYOTIC ANALOGS FOR STEROID RECEPTOR ACTION 723 Selective Promotor Activation by DNA-Binding Factors 723 Specific Antiterminator Effects 724 Gene Regulation by Protein Factors Bound to RNA Polymerase 724 DNA-Binding Specificities of Prokaryotic Gene Regulators 725 DNA· BINDING STUDIES ON STEROID RECEPTORS 726 Ability of Receptor Aggregation to Mimic DNA Binding 726 Methods for Quantitating Binding 726 Artifactual Saturation of DNA Binding 726 Biological Relevance of DNA Binding 727 BIOLOGICAL CHARACTERISTICS OF STEROID RECEPTOR ACTION 727 Receptor·Nucleus Interaction In Vivo 727 Dose·Response Relationships 728 The Detection of the Primary Response 728 Biologically Specific and Nonspecific Interactions 730

Metabolism and mechanism of action of vitamin D.

Abstract: Progress in the definition of mechanism of action of Vitamin D indicates that the vitamin functions as a prohormone giving rise to at least one hormone that plays a central role in the metabolism of calcium and phosphorus. Vitamin D3 is converted to 25-hydroxyvitamin D3 (25-OH-D3) in the liver. This compound, which can be regarded as the major circulating metabolite of Vitamin D does not act directly at physiologic concentrations but is altered in the kidney to I alpha, 25-dihydroxy-vitamin D3. It is this form of Vitamin D which is then transferred to the intestine, bone, and kidney where it or a further metabolite stimulates intestinal calcium transport, intestinal phosphate transport, the mobilization of calcium from bones, and renal absorption of calcium. Evidence has been presented for the existence of a receptor protein in intestinal mucosa that binds specifically I alpha, 25-dihydroxyvitamin in D3 and that may function in the nucleus to initiate transcription of genomes that code for proteins involved in the transport phenomenon. The discovery of this new endocrine system has brought with it many implications for the understanding and treatment of metabolic bone disease. (MFB)

Transfer RNA: Molecular Structure, Sequence, and Properties

Abstract: INTRODUCTION THE MULTIPLE BIOLOGICAL FUNCTIONS OF tRNA . tRNA Cycle in Protein Synthesis . tRNA and the Regulation of Enzyme Synthesis . Aminoacyl-tRNA Transferases . tRNA Participation in Polynucleotide Synthesis . tRNA as an Enzyme Inhibitor . tRNA Changes in Cells .

The Red Cell Membrane

Abstract: PERSPECTIVES AND SUMMARy 667 INTRODUCTION 668 POLYPEPTIDES OF THE HUMAN RED CELL MEMBRANE 669 A Provisional Model for the Arrangement of the Major Proteins . . 671 Location 0/ extrinsic membrane proteins 672 The integral membrane proteins 676 The sialoglycopeptides (PAS-I, PAS-2, glycophorin A) 677 PAS-3 and the minor glycopeptides 684

Translational Control of Protein Synthesis

Abstract: TRANSCRIPTIONAL CONTROL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 REGULATION OF mRNA TRANSLATION AT THE INITIATION STEP 41 INITIATION OF PROTEIN SYNTHESIS ...... 41 TRANSLATIONAL CONTROL OF PROTEIN SYNTHESIS . . ........ ..... 43 MODEL FOR PROTEIN SYNTHESIS ..... 44 SPECIFICITY IN TRANSLATION OF BACTERIAL mRNA . ... .... . ... 1 46 SEQUENCES ON mRNA-SPECIFYING CHAIN INITIATION 47 TRANSLATIONAL CONTROL IN THE RNA BACTERIOPHAGES ... 49 TRANSLATION OF POLYGENIC mRNAs .. ........ .... .... . ..... 50 VIRUS-MEDIATED PERTURBATIONS OF THE BACTERIAL TRANSLATION APPARATUS 5 1 MESSENGER RNA IN EUKARYOTIC CELLS ........ . 53 MODIFICATIONS AT THE ENDS OF EUKARYOTIC mRNA . . . . . . . . . .. . . .. . . . . . . . . . . . . . . . . . . . . . . . . 5 5 REGULATION O F THE OVERALL RATE O F POLYPEPTIDE CHAIN INITIATION .... 56 RELATIVE RATES OF INITIATION OF TRANSLATION OF DIFFERENT EUKARYOTIC mRNAs ...... ..... ...... ... . 58 SPECIFICITY IN TRANSLATION OF EUKARYOTIC mRNA 58 MESSAGE-S1?,ECIFIC FACTORS 60 VIRUS-MEDIATED PERTURBATION OF EUKARYOTIC CELL PROTEIN SYNTHESIS . .... .... ... ....... ... ... ........ 62 CONCLUSION ...... ... . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .. ... . . .. . .. . . ........ ..... ... . .. . ... .. ... . . . . . . . . . . 63

Processing of RNA.

Abstract: CONTENTS PERSPECTIVES AND SUMMARY tRNA . Prokaryotes , . Eukaryotes . rRNA . Prokaryotes , , , ... .

The Biochemistry of Mutagenesis

Abstract: Mutagenesis has remained an intriguing aspect of genetics since the beginning of this century, and its analysis has proceeded hand in hand with the elucidation of gene replication and expression. Interest in this area has further heightened with the growing awareness that numerous environmental agents may cause mutations in humans. These mutations may lead to metabolic as well as neoplastic diseases. Advances during the past 15 years have revealed two major classes of mutagenic mechanisms: directly induced base mispairing, and misrepair. Alkylating agents for instance, generate many different reaction products in DNA, but only two of these (O6-alkylguanine and O4-alkylthymine) are likely candidates for directly induced mispairing. He has also turned out to be an important mutagen, one that presents a particular serious challenge to large genomes; it converts cytosine to uracil and guanine to an analogue of cytosine. DNA lesions that interrupt DNA chain elongation, including many of other products of alkylation, often trigger an error-prone postreplication repair process. Current evidence suggests that this process involves in incorrect insertion of bases into gaps in progeny-strand DNA opposite such a lesion. Mutagenic mechanisms are subject to powerful genetic controls that include the activities of DNA polymerases in the selection of deoxynucleoside triphosphates and the removal of incorrectly inserted nucleotides.

Peroxidase-Catalyzed Halogenation

Abstract: Peroxidase-catalyzed halogenation reactions have been established as being important in the biosynthesis of the hormone thyroxine and in biological defense mechanisms. Recently these reactions have been recognized as valuable tools for the study of proteins as well as their arrangement in macromolecular structures. The pathways of peroxidase catalyses can be accommodated within the framework of the classical Chance-George mechanism. This implies that the initial steps of the reaction invariably involve oxidation of peroxidases by peroxides--and that the resulting derivative, compound I, is the oxidant of the halide ions. Such reactions may result either in the formation of hypohalous acids, or in halogenation of the enzyme apoprotein, followed by transhalogenation to substrate for halogenation. Chloro- and myeloperoxidases catalyze oxidation of all halide ions, except F-; oxidation of bromide and iodide is mediated by lactoperoxidase, but horseradish peroxidase only oxidizes iodide. All of the above enzymes except horseradish will oxidize the pseudo halide thiocyanate. The origins of this differentiation remain to be defined, but they presumably reflect significant variation in oxidation potential of different peroxidase-peroxide derivatives, rather than constraints on the peroxidase-donor interactions. As pointed out above, halogenation of the amino acids tyrosine and histidine or these residues in proteins can take place on the enzyme. This makes lactoperoxidase-catalyzed iodination selective. The amino acid residues in proteins that are iodinated depend not only on reactivity of the amino acid residue but also on its geometric location. Thus lactoperoxidase-catalyzed iodination can be a useful tool in the study of protein structure and function. It is also useful in establishing the geometric position of proteins within macromolecular structures. Thyroid peroxidase catalyzes iodination of thyroglobulin and is involved in a second important step, the coupling of the iodotyrosines to form thyroxine or triiodothyronine. A proposed mechanism for this reaction suggests that the oxidation is mediated by the iodoenzyme derivative mentioned above followed by a prototropic rearrangement and scission to form the ether bound of thyronine and a serine residue on thyroglobulin.

Biochemistry and Physiology of Microtubules

Abstract: PERSPECTIVES AND SUMMARY TUBULIN BIOCHEMISTRY . Subunit Structure . Interaction of Tubulin with Small Molecules """""""'",,'''''',,''''''',''''''''''''''''''''''' Binding to Other Macromolecules .

Soluble factors required for eukaryotic protein synthesis.

Abstract: INTRODUCTION ...... ...... ....... .... ........ 191 INITIA nON . . ......... ...... ..... ........ ..... 192 Initiation Factors 192 Mechanism of Formation of the Initiation Complex 198 Other Factors Affecting Initiation 201 Messenger Selection and Recognition of Initiation Sequences by Ribosomes ........ 202

Biochemistry of Polyisoprenoid Biosynthesis

Abstract: CONTENTS PERSPECTIVES AND SUMMARy 113 INTRODUCTION ...... 114 BIOSYNTHESIS OF MEV ALONATE . ... . . . . ..... .... liS Mevalonate Biosynthesis by a Soluble Enzyme System 116 Mevalonate Biosynthesis by a Microsomal Plus Soluble Enzyme System ...... 116 BIOSYNTHESIS OF PRENYL PYROPHOSPHATES 120 Biosynthesis o/Isopentenyl Pyrophosphate 120 Biosynthesis 0/ Ally/ic Pyrophosphates 123 CwSpecijic Prenyl Trans/erases 125 C}O-Specijic Prenyl Trans/erases 126 Long-Chain Prenyl Trans/erases 127 Biosynthesis 0/ Dolichols . . . . . ......... ........ .. .. .. 127 BIOSYNTHESIS OF SQUALENE 128 BIOSYNTHESIS OF CAROTENES ..... ...... . . . .. ..... 132 Formation 0/ Phytoene .. .

Some Pertinent Aspects of Mechanism as Determined with Small Molecules

Abstract: CONTENTS INTRODUCTION CONCERTEDNESS-THE METHOD OF ALTERNATE ROUTES . Heavy-Atom and Proton Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Glycoside and acetal hydrolysis . General catalysis in acyl transfer reactions . Push-pull catalysis and the enolization of aldehydes and ketones . Electron and Proton Transfer . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . Charge Relays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PROPINQUITY-THE COMMON SENSE PHENOMENON .. STERIC RECOGNITION . FUNCTIONALITIES-PROSTHETiC GROUPS . Pyridoxal Transamination .. Dihydronicotinamides . Flavins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . Biotin ........ . Iron-Sulfur Cluster Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

The Reovirus Replicative Cycle

Abstract: Soon after entry into their host cells ssRNA viruses form doule-stranded replicative intermediates. Most RNA viruses exist only transiently in this double-stranded form. Double-strand formation occurs irrespective of whether the genome is of the same or complementary polarity to viral mRNA. In contrast, reoviruses contain dsRNAs from the outset. Single, and not double, strands are the intracellular intermediates through which genetic information is transferred from parental to progeny reoviruses. Double strands are the repositories in which the information is stored. We emphasize this distinction because it permits dsRNA-containing viruses to replicate conservatively, a mode of replication that is not shared by any other viruses. One important consequence of the conservative mode of replication is that cellular enzymes never gain access to the reovirus genome but only to its ssRNA precursors.

Photoregulation of Biologically Active Macromolecules

Abstract: A broad view is given of photoregulated processes as they occur in algae, fungi, halophilic bacteria, higher plants, invertebrates, and higher animals. Emphasis is on the following: the organs, tissues, and organelles that participate; the nature of the photoreceptor pigments; the light-induced structural changes that occur in the photopigments; and the way in which the photochemical events are believed to be translated into the physiological response. An attempt is made to show that there exist common biochemical attributes in all systems. In particular, they depend upon the ability of a low-molecular-weight to regulate a biologically active macromolecule, which may or may not be incorporated into a membrane. This is a common type of biochemical regulation and is, for example, the basis of allosterism. The additional refinement in photosensitive systems is the ability of light to alter the stereochemistry of the low-molecular-weight effector molecule and thus to modify its effect on the macromolecule. Model photosensitive systems are examined that incorporate control mechanisms that function in natural systems. For example, there are systems in which enzymes, normally insensitive to light, are made subject to photoregulation. In others, membrane permeability is rendered photoresponsive. A comparison of the model systems was processes found in nature permits the formulation of an hypothesis to explain how naturally occurring photoresponsive systems might have evolved.

Recognition mechanisms of DNA-specific enzymes.

Abstract: CONTENTS PERSPECTIVES AND SUMMARY . . . . . . . . ... . . . ... . ...... . .... 889 STRUCTURAL FEATURES OF DNA AND FUNCTIONAL IMPLICATIONS ... . .. 891 Helical Conformations 891 Interactions with Solvent and Solute ....... 892 Local Structural Fluctuations Involved in Recognition and Probes ..... ..... ... . 894 Specific Sequences and Symmetry 897 FEATURES OF PROTEIN (ENZYME)--NUCLEIC ACID INTERACTIONS . .. . . . . . 899 Protein Structure and Environmental Influences 899 Binding Equilibria . ... . . ........ ... .... ...... . . ........ ... .... . . .. . . . . . . . . . . ... ... . . . . . . . . . . . . . 900 Binding Kinetics 901 PROPERTIES OF SELECTED SYSTEMS ...... 904 DNA Polymerases 905 E. coli DNA Unwinding Protein . . . . . . . .. . ..... .. ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 907 DNA-Dependent A TPases 908 DNA Relaxing Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . 909 Repressor-Operator and RNA Polymerase-Promoter Interactions 9 1 1 CONCLUSION .. . ... . .. .. . ... . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 913

The biological origin of antibody diversity.

Abstract: Antibody diversity has a compelling fascination for many scientists and over the years speculations have sometimes seemed more numerous than facts. Now the structural basis of antibody specificity is well defined. Amino acid sequences and recently three-dimensional structures of various immunoglobulins provide the most solid basis for discussing the origin of diversity. The novel pattern of variable (V) and Constant (C) regions of amino acid sequence has been resolved further to show the functional pattern of variability. Inheritance of separate V and C genes is accepted, but attempts to define more than one gene coding for each V region are considered here to be unnecessary. The pattern of variability is still best understood in terms of mutation and the presence or absence of various selective pressures. The major area of debate still hinges around the extent to which mutation and selection operate during evolution or somatically. Sequence data have now been generally interpreted to require multiple V genes carried in the germ line. A few individual VH genes have been mapped in close linkage to CH genes in the mouse. The apparent existence of three VH alleles in rabbits was a strong argument against multiple V genes. Now the three phenotypes have been shown to be due to alleles controlling the expression of three sets of VH genes all present on the same chromosome. That V-gene expression requires rejoining of V and C genes at the DNA level is now almost certain. Models for the joining process can draw on the precedents of transposable genetic elements, which are widespread in Nature. The total extent of antibody diversity remains a philosophical point. Estimates of the number of antibody molecules required for observed diversity are reduced by two recently documented proposals. Each antibody combining site apparently has many (estimated at 100) different specificities and most combinations of VH and VL regions probably form a viable site. A given combining site can be defined by its pattern of shared specificities. Several specific antibody repertoires have been measured and the size in each case is consistent with the stringency with which the specificity is selected. Repertoire size appears to be under genetic control, but there are problems in viewing the genotype through the veil of clonal selection. Molecular hybridization has been used recently in an attempt to count V and C genes directly. C genes are seen in DNA having nonreiterated sequences, as formal genetics predicts. Each V-region probe hybridizes at a similar rate to C-region probes. Interpretation of this result depends on the extent to which one V-region probe will reveal nonhomologous V genes. Previous estimates that many cross-hybridizing genes should have been seen if present are possibly exaggerated. It is argued here that the data are compatible with a germ-line gene for each probe studied. Maximum estimates for the number of germ-line genes are sufficient to account for antibody diversity...

Concepts and perspectives in enzyme stereochemistry

Abstract: CONCEPTS Examination for Equivalence and Symmetry . Factorization .. . . . ..... . . . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ . Stereoheterotopic Faces .: .... ......... . . . . . CORRELATION NETWORKS . Lirerature Management . Key Intermediates .