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Cold Spring Harbor Perspectives in... Sep 2019Protein synthesis involves a complex machinery comprising numerous proteins and RNAs joined by noncovalent interactions. Its function is to link long chains of amino... (Review)
Review
Protein synthesis involves a complex machinery comprising numerous proteins and RNAs joined by noncovalent interactions. Its function is to link long chains of amino acids into proteins with precise sequences as encoded by the genome. Regulation of protein synthesis, called translational control, occurs both at a global level and at specific messenger RNAs (mRNAs). To understand how translation is regulated, knowledge of the molecular structures and kinetic interactions of its components is needed. This review focuses on the targets of translational control and the mechanisms employed.
Topics: 5' Untranslated Regions; Codon; Cytoplasm; Gene Expression Regulation; Genome; Kinetics; Phosphorylation; Protein Biosynthesis; Protein Conformation; Protein Processing, Post-Translational; Proteins; RNA; RNA, Messenger; Ribosomes
PubMed: 29959195
DOI: 10.1101/cshperspect.a032607 -
The Journal of Biological Chemistry Nov 2015Emerging evidence indicates that protein synthesis and degradation are necessary for the remodeling of synapses. These two processes govern cellular protein turnover,... (Review)
Review
Emerging evidence indicates that protein synthesis and degradation are necessary for the remodeling of synapses. These two processes govern cellular protein turnover, are tightly regulated, and are modulated by neuronal activity in time and space. The anisotropic anatomy of the neurons presents a challenge for the study of protein turnover, but the understanding of protein turnover in neurons and its modulation in response to activity can help us to unravel the fine-tuned changes that occur at synapses in response to activity. Here we review the key experimental evidence demonstrating the role of protein synthesis and degradation in synaptic plasticity, as well as the turnover rates of specific neuronal proteins.
Topics: Animals; Humans; Nerve Tissue Proteins; Neurons; Protein Biosynthesis; Proteolysis; Synapses
PubMed: 26453306
DOI: 10.1074/jbc.R115.657130 -
Molecules (Basel, Switzerland) Aug 2017The many advances in glycoscience have more and more brought to light the crucial role of glycosides and glycoconjugates in biological processes. Their major influence... (Review)
Review
The many advances in glycoscience have more and more brought to light the crucial role of glycosides and glycoconjugates in biological processes. Their major influence on the functionality and stability of peptides, cell recognition, health and immunity and many other processes throughout biology has increased the demand for simple synthetic methods allowing the defined syntheses of target glycosides. Additional interest in glycoside synthesis has arisen with the prospect of producing sustainable materials from these abundant polymers. Enzymatic synthesis has proven itself to be a promising alternative to the laborious chemical synthesis of glycosides by avoiding the necessity of numerous protecting group strategies. Among the biocatalytic strategies, glycosynthases, genetically engineered glycosidases void of hydrolytic activity, have gained much interest in recent years, enabling not only the selective synthesis of small glycosides and glycoconjugates, but also the production of highly functionalized polysaccharides. This review provides a detailed overview over the glycosylation possibilities of the variety of glycosynthases produced until now, focusing on the transfer of the most common glucosyl-, galactosyl-, xylosyl-, mannosyl-, fucosyl-residues and of whole glycan blocks by the different glycosynthase enzyme variants.
Topics: Animals; Biocatalysis; Glycoside Hydrolases; Glycosides; Glycosylation; Humans
PubMed: 28867807
DOI: 10.3390/molecules22091434 -
Nature Chemistry Nov 2020All living organisms synthesize phospholipids as the primary constituent of their cell membranes. Enzymatic synthesis of diacylphospholipids requires preexisting...
All living organisms synthesize phospholipids as the primary constituent of their cell membranes. Enzymatic synthesis of diacylphospholipids requires preexisting membrane-embedded enzymes. This limitation has led to models of early life in which the first cells used simpler types of membrane building blocks and has hampered integration of phospholipid synthesis into artificial cells. Here we demonstrate an enzyme-free synthesis of natural diacylphospholipids by transacylation in water, which is enabled by a combination of ion pairing and self-assembly between lysophospholipids and acyl donors. A variety of membrane-forming cellular phospholipids have been obtained in high yields. Membrane formation takes place in water from natural alkaline sources such as soda lakes and hydrothermal oceanic vents. When formed vesicles are transferred to more acidic solutions, electrochemical proton gradients are spontaneously established and maintained. This high-yielding non-enzymatic synthesis of natural phospholipids in water opens up new routes for lipid synthesis in artificial cells and sheds light on the origin and evolution of cellular membranes.
Topics: Acylation; Artificial Cells; Cell Membrane; Phospholipids; Protein Biosynthesis; Water
PubMed: 33046841
DOI: 10.1038/s41557-020-00559-0 -
Scientific Reports Feb 2022The aims of the current study, therefore, were to compare (1) free-living MPS and (2) muscle and metabolic adaptations to resistance exercise in South Asian and white...
The aims of the current study, therefore, were to compare (1) free-living MPS and (2) muscle and metabolic adaptations to resistance exercise in South Asian and white European adults. Eighteen South Asian and 16 White European men were enrolled in the study. Free-living muscle protein synthesis was measured at baseline. Muscle strength, body composition, resting metabolic rate, VO and metabolic responses (insulin sensitivity) to a mixed meal were measured at baseline and following 12 weeks of resistance exercise training. Free-living muscle protein synthesis was not different between South Asians (1.48 ± 0.09%/day) and White Europeans (1.59 ± 0.15%/day) (p = 0.522). In response to resistance exercise training there were no differences, between South Asians and White Europeans, muscle mass, lower body strength or insulin sensitivity. However, there were differences between the ethnicities in response to resistance exercise training in body fat, resting carbohydrate and fat metabolism, blood pressure, VO and upper body strength with responses less favourable in South Asians. In this exploratory study there were no differences in muscle protein synthesis or anabolic and metabolic responses to resistance exercise, yet there were less favourable responses in several outcomes. These findings require further investigation.
Topics: Adipose Tissue; Adult; Asia, Southeastern; Asian People; Body Composition; Carbohydrate Metabolism; Europe; Exercise; Humans; Insulin Resistance; Lipid Metabolism; Male; Muscle Proteins; Muscle Strength; Muscle, Skeletal; Resistance Training; White People; Young Adult
PubMed: 35169204
DOI: 10.1038/s41598-022-06446-7 -
PloS One 2021Heme is an essential cofactor for enzymes of the electron transport chain (ETC) and ATP synthesis in mitochondrial oxidative phosphorylation (OXPHOS). Heme also binds to...
Heme is an essential cofactor for enzymes of the electron transport chain (ETC) and ATP synthesis in mitochondrial oxidative phosphorylation (OXPHOS). Heme also binds to and destabilizes Bach1, a transcription regulator that controls expression of several groups of genes important for glycolysis, ETC, and metastasis of cancer cells. Heme synthesis can thus affect pathways through which cells generate energy and precursors for anabolism. In addition, increased heme synthesis may trigger oxidative stress. Since many cancers are characterized by a high glycolytic rate regardless of oxygen availability, targeting glycolysis, ETC, and OXPHOS have emerged as a potential therapeutic strategy. Here, we report that enhancing heme synthesis through exogenous supplementation of heme precursor 5-aminolevulinic acid (ALA) suppresses oxidative metabolism as well as glycolysis and significantly reduces proliferation of both ovarian and breast cancer cells. ALA supplementation also destabilizes Bach1 and inhibits migration of both cell types. Our data indicate that the underlying mechanisms differ in ovarian and breast cancer cells, but involve destabilization of Bach1, AMPK activation, and induction of oxidative stress. In addition, there appears to be an inverse correlation between the activity of oxidative metabolism and ALA sensitivity. Promoting heme synthesis by ALA supplementation may thus represent a promising new anti-cancer strategy, particularly in cancers that are sensitive to altered redox signaling, or in combination with strategies that target the antioxidant systems or metabolic weaknesses of cancer cells.
Topics: Biosynthetic Pathways; Breast Neoplasms; Cell Line, Tumor; Female; Glycolysis; Heme; Humans; Ovarian Neoplasms; Oxidative Stress; Warburg Effect, Oncologic
PubMed: 34807950
DOI: 10.1371/journal.pone.0260400 -
Current Opinion in Microbiology Jun 2016Microbial growth can be characterized by a limited set of macroscopic parameters such as growth rate, biomass yield and substrate affinity. Different culturing protocols... (Review)
Review
Microbial growth can be characterized by a limited set of macroscopic parameters such as growth rate, biomass yield and substrate affinity. Different culturing protocols for laboratory evolution have been developed to select mutant strains that have one specific macroscopic growth parameter improved. Some of those mutant strains display tradeoffs between growth parameters and changed metabolic strategies, for example, a shift from respiration to fermentation. Here we discuss recent studies suggesting that metabolic strategies and growth parameter tradeoffs originate from a common set of physicochemical and cellular constraints, associated with the allocation of intracellular resources over biosynthetic processes, mostly protein synthesis. This knowledge will give insight in ecological and biological concepts and can be used for metabolic and evolutionary engineering strategies.
Topics: Adaptation, Physiological; Bacteria; Biomass; Fermentation; Protein Biosynthesis
PubMed: 27054480
DOI: 10.1016/j.mib.2016.03.007 -
Trends in Molecular Medicine Jan 2020Mitochondria have emerged as important pharmacological targets because of their key role in cellular proliferation and death. In tumor tissues, mitochondria can switch... (Review)
Review
Mitochondria have emerged as important pharmacological targets because of their key role in cellular proliferation and death. In tumor tissues, mitochondria can switch metabolic phenotypes to meet the challenges of high energy demand and macromolecular synthesis. Furthermore, mitochondria can engage in crosstalk with the tumor microenvironment, and signals from cancer-associated fibroblasts can impinge on mitochondria. Cancer cells can also acquire a hybrid phenotype in which both glycolysis and oxidative phosphorylation (OXPHOS) can be utilized. This hybrid phenotype can facilitate metabolic plasticity of cancer cells more specifically in metastasis and therapy-resistance. In light of the metabolic heterogeneity and plasticity of cancer cells that had until recently remained unappreciated, strategies targeting cancer metabolic dependency appear to be promising in the development of novel and effective cancer therapeutics.
Topics: Animals; Energy Metabolism; Glycolysis; Humans; Mitochondria; Neoplasms; Oxidative Phosphorylation; Tumor Microenvironment
PubMed: 31327706
DOI: 10.1016/j.molmed.2019.06.009 -
IUBMB Life Mar 2013In nonphotosynthetic organisms, mitochondria are the power plant of the cell, emphasizing their great potentiality for adenosine triphosphate (ATP) synthesis from the... (Review)
Review
In nonphotosynthetic organisms, mitochondria are the power plant of the cell, emphasizing their great potentiality for adenosine triphosphate (ATP) synthesis from the redox span between nutrients and oxygen. Also of great importance is their role in the maintenance of the cell redox balance. Even though crystallographic structures of respiratory complexes, ATP synthase, and ATP/adenosine diphosphate (ADP) carrier are now quite well known, the coupling between ATP synthesis and cell redox state remains a controversial issue. In this review, we will present some of the processes that allow a modular coupling between ATP synthesis and redox state. Furthermore, we will present some theoretical approaches of this highly integrated system.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Biological Transport; Electron Transport; Energy Metabolism; Fungi; Humans; Kinetics; Mitochondria; Models, Chemical; Oxidation-Reduction; Oxidative Phosphorylation; Oxygen; Thermodynamics
PubMed: 23441039
DOI: 10.1002/iub.1138 -
Plant Physiology Sep 2013The plant cuticle is an extracellular hydrophobic layer that covers the aerial epidermis of all land plants, providing protection against desiccation and external... (Review)
Review
The plant cuticle is an extracellular hydrophobic layer that covers the aerial epidermis of all land plants, providing protection against desiccation and external environmental stresses. The past decade has seen considerable progress in assembling models for the biosynthesis of its two major components, the polymer cutin and cuticular waxes. Most recently, two breakthroughs in the long-sought molecular bases of alkane formation and polyester synthesis have allowed construction of nearly complete biosynthetic pathways for both waxes and cutin. Concurrently, a complex regulatory network controlling the synthesis of the cuticle is emerging. It has also become clear that the physiological role of the cuticle extends well beyond its primary function as a transpiration barrier, playing important roles in processes ranging from development to interaction with microbes. Here, we review recent progress in the biochemistry and molecular biology of cuticle synthesis and function and highlight some of the major questions that will drive future research in this field.
Topics: Acyltransferases; Biological Transport; Biosynthetic Pathways; Gene Expression Regulation, Plant; Genes, Plant; Lipid Metabolism; Membrane Lipids; Mixed Function Oxygenases; Plants; Polymerization; Waxes
PubMed: 23893170
DOI: 10.1104/pp.113.222737