Selenium : Its Molecular Biology and Role in Human Health

Many health benefits have been attributed to selenium that include preventing various forms of cancer (e.g., colon cancer, prostate cancer, lung cancer and liver cancer), heart disease and other cardiovascular and muscle disorders, inhibiting viral expression, delaying the progression of acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-positive patients, slowing the aging process, and having roles in mammalian development, including male reproduction and immune function. The purpose of the book is the same as the first three volumes which is to bring an up to date status of current research in the rapidly developing selenium field centered around the health benefits attributed to this element and how this element makes its way into protein. Dedication......Page 6 Foreword......Page 10 Reference......Page 12 Preface......Page 14 Acknowledgements......Page 16 Contents......Page 18 Contributors......Page 24 Part I: The Machinery of Selenoprotein Biosynthesis......Page 33 Chapter 1: Selenocysteine tRNA[Ser]Sec: From Nonsense Suppressor tRNA to the Quintessential Constituent in Selenoprotein Biosynthesis......Page 34 1.2 Primary and Secondary Structures of Sec tRNA......Page 35 1.3 Um34 Addition to Sec tRNA[Ser]Sec, a Most Highly Specialized Modification......Page 36 1.4 Trsp, the Sec tRNA[Ser]Sec Gene......Page 38 1.5 Transcription of Trsp......Page 39 1.7 Crystallization of tRNA[Ser]Sec......Page 40 1.8 Concluding Remarks......Page 41 References......Page 42 2.1 Introduction......Page 44 2.2 UGA Recoding......Page 45 2.3 SECIS......Page 46 2.4 SECIS Binding Protein 2......Page 47 2.5 Sec-Specific Elongation Factor......Page 48 2.6 Other Factors......Page 49 2.8 Impact of In Vitro Translation Systems for Studying Sec Incorporation......Page 51 2.9 Concluding Remarks......Page 52 References......Page 53 3.1 Introduction......Page 56 3.2 Translational Control of Gene Expression Revealed by Ribosome Profiling......Page 58 3.3 Application of Ribosome Profiling to Investigate Selenoprotein Biosynthesis......Page 61 3.3.2 Ribosome Occupancy Near the UGA-Sec Codon and in the 5′ UTR......Page 64 3.4 Conclusion: Insights Gained, Limitations, and Future Directions......Page 65 References......Page 67 4.1 Introduction......Page 69 4.2 Sec Biosynthesis......Page 70 4.2.2 Step 1: Aminoacylation of tRNA[Ser]Sec......Page 71 4.2.5 Sec Synthesis......Page 72 4.3.2 In Vitro Studies......Page 73 4.4 Concluding Remarks......Page 74 References......Page 75 5.1 Introduction......Page 76 5.3.1 Sec Biosynthesis and Incorporation in E. coli......Page 77 5.3.2 Selenoprotein Synthesis in Other Bacteria......Page 79 5.4 Selenoprotein Synthesis in Archaea......Page 80 5.5 Selenoproteins of Prokaryotes......Page 81 5.5.2 Formate Dehydrogenase......Page 82 5.5.6 Methionine Sulfoxide Reductase......Page 83 5.5.10 HesB-Like Selenoprotein......Page 84 References......Page 85 6.1 Introduction......Page 88 6.2 Diet and Natural Selection......Page 89 6.3 Worldwide Availability of Se......Page 90 6.4 Genetic Variation in Human Se-Related Genes......Page 91 6.5 Human Adaptation to Dietary Se......Page 92 6.7 Genes That May Be Important for Adaptation to Se Deficiency......Page 95 6.8 Concluding Remarks......Page 98 References......Page 99 7.1 Selenocysteine in Chemical Protein Synthesis......Page 101 7.2 Selenocysteine in Oxidative Protein Folding......Page 105 7.3 SEP15 and SELM in In Vivo Protein Folding......Page 108 7.4 Concluding Remarks......Page 109 References......Page 110 Chapter 8: Evolution of Selenophosphate Synthetase......Page 112 8.1 Introduction......Page 113 8.2.1 Bacteria......Page 117 8.2.2 Archaea......Page 119 8.3.1 Emergence of SPS1 Genes in Metazoa......Page 120 References......Page 125 9.1 Introduction......Page 127 9.2 The Structure and Architecture of the Bacterial SelA......Page 130 9.3 The Structure of the Archaeal and Eukaryotic SepSecS......Page 132 9.4 Divergent Active Sites of Selenocysteine Synthases and a Conserved Catalytic Mechanism......Page 133 References......Page 136 10.1 Mammalian Selenium Metabolism......Page 139 10.2 Identification of SCLY in Mammals and Bacteria......Page 141 10.4 Homology to NifS-type Cysteine Desulfurases......Page 142 10.5 Structure and Open-Close Conformational Change......Page 143 10.6 Catalytic Mechanism......Page 144 10.7 Discrimination Between Selenium and Sulfur......Page 146 10.8 Biological Role......Page 147 References......Page 148 Part II: Selenoproteins, Their Occurrence and Function......Page 150 11.1 Introduction......Page 151 11.2 Computational Tools for Selenoprotein Identification......Page 152 11.3.1 Glutathione Peroxidases......Page 153 11.3.3 Thioredoxin Reductases......Page 154 11.3.6 Selenophosphate Synthetase 2 (SEPHS2)......Page 155 11.3.10 Selenoproteins O (SELO) and I (SELI)......Page 156 11.4 Additional Selenoproteins in Eukaryotes......Page 157 11.6 Selenoproteomes......Page 158 11.7.2 High-Throughput Identification of Catalytic Redox-­Active Cysteine Residues......Page 160 11.9 Concluding Remarks......Page 161 References......Page 162 12.1 Introduction......Page 164 12.2 Computational Identification of Selenoproteins in Prokaryotes......Page 165 12.3 Prokaryotic Selenoproteins......Page 167 12.4 Comparative Genomics of Selenoproteomes in Prokaryotes......Page 170 References......Page 172 13.1 Introduction......Page 174 13.2 Selenium Metabolism and Transport......Page 175 13.3 The Effects of SNPs on the Sec Incorporation Machinery......Page 189 13.4.1 Genetic Variants in GPX4......Page 190 13.4.2 Genetic Variants in GPX1......Page 191 13.5 Genetics of Endoplasmic Reticulum Selenoproteins......Page 192 13.6 Perspectives......Page 193 References......Page 194 14.1 Introduction......Page 197 14.2 Animal Models for Se Regulation of Selenoprotein Transcripts......Page 198 14.4 Se Regulation of Selenoprotein Transcripts in Rats......Page 199 14.6 Se Regulation of Selenoprotein Transcripts in Turkeys......Page 201 14.8 Se Regulation of Selenoprotein Transcripts in Caenorhabditis elegans......Page 202 14.9 Overall Selenoprotein Transcript Regulation......Page 203 14.10 Se Regulation of Non-selenoprotein Transcripts in Rodents......Page 204 14.12 Se Regulation of Non-selenoprotein Transcripts in Avian Species......Page 206 References......Page 207 15.1 NMR Spectroscopy of Biological Macromolecules......Page 209 15.2 Selenium’s NMR Properties......Page 210 15.3 77Se Isotopic Enrichment of Proteins for NMR Studies......Page 211 15.4 Identification of Chemical Species by 77Se NMR......Page 213 15.6 Measurements of Sec pKa in Selenoproteins and Selenopeptides......Page 215 15.8 77Se NMR Sensitivity to the Local Environment......Page 216 15.10 Concluding Remarks......Page 218 References......Page 219 16.1 Introduction......Page 221 16.3 The Interplay Between Thioredoxin Reductase and Nrf2......Page 222 16.4 Impact of Thioredoxin Reductase Targeting in Cancer and Its Potential for New Anticancer Therapy......Page 223 16.5.1 Nrf2 Activation, with Increased Detoxifying Protection Against Carcinogens and Inhibited Initiation or Transformation......Page 224 16.5.4 Impaired Angiogenesis upon TrxR1 Inhibition......Page 225 16.6 Potential Cancer-Promoting Effects of TrxR1 Drug Targeting......Page 226 16.6.2 Increased Cancer-Promoting Mutagenesis Due to Increased ROS Levels after TrxR1 Targeting......Page 227 16.6.4 Nrf2 Activation in Cancer Cells, with Increased Cancer Cell Robustness......Page 228 References......Page 229 17.1 Introduction......Page 232 17.2 The Glutathione Peroxidase Reaction......Page 233 17.3.1 Structure and Substrate Specificity......Page 236 17.3.2 Diversified Biological Roles......Page 237 17.4 Concluding Remarks......Page 240 References......Page 241 18.1 Introduction......Page 244 18.4 Enzymatic Activity......Page 245 18.6 Catalytic Mechanism......Page 246 18.8 Genetic Diseases and Polymorphisms......Page 248 18.9 Male Fertility......Page 249 18.11 Cell Death and Survival......Page 250 18.13 Viral Diseases......Page 252 18.14 Conclusions, Unresolved Questions, and Perspectives......Page 253 References......Page 254 19.1 Introduction......Page 256 19.2 SEP15 Structure and Function......Page 257 19.3 Biological Function of SEP15......Page 259 19.4 Human SEP15 Polymorphisms and Cancer......Page 261 References......Page 263 20.1 Introduction......Page 265 20.3 The Role of SELK-Dependent Palmitoylation in Regulating the Stability and Function of CD36......Page 267 20.4 The Role of SELK-Dependent Palmitoylation in Regulating the Function of the IP3R......Page 268 20.5 How Does SELK Contribute to Protein Palmitoylation?......Page 270 References......Page 271 21.1 Discovery and Structure......Page 273 21.2 Expression......Page 274 21.3 Role in Neuroprotection......Page 276 21.4 Characterization of the Selm Knockout Mouse......Page 277 21.5 Involvement in Cancer......Page 278 References......Page 279 Chapter 22: Selenoprotein P and Selenium Distribution in Mammals......Page 281 22.2 Selenoprotein P (Sepp) Is a Plasma Selenium Transport Protein......Page 282 22.3 Lipoprotein Receptor-Related Proteins as Endocytic Receptors Involved in Sepp Uptake......Page 283 22.4.1 Classical Gene Targeting......Page 284 22.4.2 Isoforms of Sepp......Page 285 22.4.3 Sepp in the Liver......Page 287 22.4.5 Sepp in the Kidney......Page 288 22.5 Regulation of Sepp Expression......Page 289 22.6 Comparison of Experimental Concepts with Clinical Data......Page 290 22.7 Concluding Remarks......Page 291 References......Page 292 23.1 Introduction......Page 295 23.2 Structure, Subcellular Localization and Activity......Page 296 23.3 Tissue-Distribution and Regulation of Gene Expression......Page 297 23.4 Function......Page 299 23.4.1 Role in Ca2+ Regulation and Cell Adhesion......Page 300 23.4.2 Role in Brain......Page 301 23.4.3 Role in Pancreas......Page 302 23.4.4 Role in Liver......Page 303 References......Page 305 Chapter 24: Biochemistry and Function of Methionine Sulfoxide Reductase......Page 307 24.2 Methionine Oxidation......Page 308 24.3 Methionine Sulfoxide Reductase Families......Page 309 24.4 Functions of Methionine Sulfoxide Reductase......Page 310 References......Page 312 Part III: Dietary Selenium and Its Impact on Human Health......Page 313 25.1 Introduction......Page 314 25.2 Geographic Distribution and Production......Page 315 25.3 Dietary Sources......Page 316 25.4 Human Se Requirements and Patterns of Consumption......Page 317 25.6 Se Intake and Se Status......Page 319 25.6.2 Se Deficiency......Page 320 25.6.3 Selenosis/Se Toxicity......Page 321 References......Page 322 26.1 Introduction......Page 325 26.2 Successful Prevention of Endemic Diseases Linked to Se Deficiency......Page 327 26.3 Clinical Trials for Biomarker Identification of Se Status......Page 329 26.4 Se and Cancer Prevention......Page 330 26.6 Se in Sepsis......Page 332 26.7 Se in Thyroid Disease......Page 333 26.9 Pregnancy......Page 334 References......Page 335 Chapter 27: Status of Dietary Selenium in Cancer Prevention......Page 338 27.1.2 Clinical Trial Results......Page 339 27.2.1 Roles of Selenocysteine-Containing Selenoproteins......Page 340 27.2.3 Roles of Selenium-Metabolites......Page 341 27.2.3.1 Effects of Selenium-Metabolites on Tumor Cells......Page 342 Modification of Protein-Thiols......Page 343 27.3 Evidence for Tumorigenic Actions of Selenoproteins......Page 344 27.5 Concluding Remarks......Page 345 References......Page 347 28.1 Introduction......Page 350 28.2 Se and Immunity......Page 351 28.3 HIV, Antiretroviral Treatment, Oxidative Stress and Se......Page 352 28.4 Observational Studies of Se Deficiency and HIV......Page 353 28.5 Se Supplementation in HIV......Page 355 28.6 Clinical Trials of Supplementation in HIV-Positive Patients that Included Se in the Experimental Formula......Page 356 References......Page 357 29.1 Introduction......Page 360 29.2 The Types of Genetic Variations to Consider......Page 361 29.3 Glutathione Peroxidase 1 (GPX1)......Page 362 29.4 The 15 kDa Selenoprotein (SEP15)......Page 364 29.6 Thioredoxin Reductases (TXNRD)......Page 365 29.8 Selenoprotein P (SEPP1) and Its Impact on Other Selenoproteins......Page 366 29.9 Concluding Remarks......Page 367 References......Page 368 30.1 Introduction......Page 370 30.2.1 Observational Studies of Se and Pre-eclampsia......Page 371 30.2.2 Se Supplementation in Pregnancy......Page 372 30.3 Miscarriage......Page 373 30.4.1 How Might Se Affect the Risk of Preterm Birth?......Page 375 30.5 Autoimmune Thyroid Disease......Page 376 30.5.1 How May Se Affect the Risk of Autoimmune Thyroid Disease in Pregnancy?......Page 377 30.6 Insulin Resistance......Page 378 References......Page 379 Chapter 31: The Epidemiology of Selenium and Human Health......Page 382 31.2 Cancer......Page 383 31.3 Cardiovascular Disease......Page 387 31.6 Neurological Disease......Page 388 31.7 Concluding Remarks......Page 390 References......Page 391 Chapter 32: Sex-Specific Differences in Biological Effects and Metabolism of Selenium......Page 394 32.1 Selenium Metabolism in Female and Male Animals......Page 395 32.2 Sex-Specific Regulation of Selenoprotein Expression......Page 396 32.3.1 Cancer......Page 398 32.3.2 Infectious Diseases and Sepsis......Page 399 32.3.3 Autoimmune Thyroid Disease......Page 400 32.3.4 Cardiovascular System......Page 401 32.5 Concluding Remarks......Page 402 References......Page 403 33.1 Introduction......Page 406 33.2 Hypothalamus–Pituitary-Feedback Axis, Selenium, and the Hormonal Regulation of Energy Metabolism......Page 407 33.3 Selenium in the Thyroid Gland and Thyroid Hormone Synthesis, Metabolism, and Action......Page 409 33.4 Selenium, Bone, and Calcium-Regulating Hormones......Page 412 33.5 The Effect of Se on Renal and Adrenal Hormones, Hypertension, and Steroid Biosynthesis......Page 413 33.6 Selenium, Glucoregulatory Hormones, and Diabetes......Page 414 References......Page 415 Chapter 34: Selenium Antagonism with Mercury and Arsenic: From Chemistry to Population Health and Demography......Page 418 34.2 Oxidative Crossroad Between Se, As and Hg......Page 419 34.3 Inflammatory Crossroads Between Se, As and Hg......Page 420 34.5 Clinical Outcome of the Hg–Se Interaction: Neurotoxicity and Neurodegeneration......Page 421 34.7 Clinical Outcome of the As–Se Interaction: Cancer......Page 423 34.9 Se-Hg Interaction and Population Health and Demography in Russia......Page 424 References......Page 427 35.1 Introduction: Interest in Selenium (Se) Speciation Analysis in Biology......Page 430 35.2.2 Selenoproteins and Se-Containing Proteins......Page 431 35.2.4 Nanoparticles and Selenodrugs......Page 432 35.4 Speciation of Protein-Bound Se and Selenoproteomics......Page 434 35.4.2.1 Bottom-Up Approach......Page 435 35.4.2.3 Top-Down Approaches and Structural Studies......Page 436 35.5 Speciation Analysis of Selenometabolites......Page 437 35.7 Concluding Remarks......Page 439 References......Page 440 Part IV: Selenoproteins in Human Health......Page 442 36.1 Reduced Brain Selenium Availability Impairs Brain Function......Page 443 36.2.1.1 Transfer RNA[Ser]Sec......Page 445 36.2.2.1 Glutatione Peroxidase 4......Page 448 36.2.2.3 Deiodinases......Page 450 36.3.1 Progressive Cerebello-Cerebral Atrophy (SEPSECS-Mutations)......Page 451 36.3.3 Deficiencies in Thioredoxin Reductases......Page 452 36.3.5 tRNA[Ser]Sec (TRNAU) Mutation in Humans......Page 453 References......Page 454 Chapter 37: Interplay of Selenoproteins and Different Antioxidant Systems in Various Cancers......Page 456 37.1 Introduction......Page 457 37.3 Selenoprotein Roles in Normal and Malignant Lung and Liver Tissues......Page 458 37.3.1 Selenoprotein Roles in Mouse Normal and Malignant Tissues......Page 459 37.3.2 Selenoprotein Roles in Human Normal and Malignant Lung and Liver Tissues......Page 460 37.5 Concluding Remarks......Page 462 References......Page 463 38.1 Introduction......Page 465 38.3 Localization......Page 466 38.4.1 Nrf2......Page 467 38.4.3 STATs......Page 468 38.5.1 Reduction of Hydroperoxides and DNA Damage......Page 469 38.5.2 Inhibition of Apoptosis......Page 470 38.5.3 Role of GPx2 in Inflammation-Driven Carcinogenesis......Page 471 38.5.4 Role of GPx2 in Neoplasia and Tumor Proliferation......Page 472 38.5.5 Metastasis......Page 473 38.6 Concluding Remarks......Page 474 References......Page 475 39.1 Introduction......Page 477 39.2 The Role of Selenoproteins in Regulating Vascular Tone......Page 478 39.3 The Role of Selenoproteins in Inflammation and Atherogenesis......Page 479 39.4 The Role of Selenoproteins in Vascular Remodeling and Angiogenesis......Page 481 39.5 The Role of Selenoproteins in Stroke and Thrombosis......Page 482 39.6 Cardiovascular Development and Selenoproteins......Page 483 39.7 Cardioprotection and Selenoproteins......Page 484 39.8 Concluding Remarks......Page 485 References......Page 487 Chapter 40: What Do We Know About Selenium Contributions to Muscle Physiology?......Page 489 40.2 Se Sources and Forms in Muscles......Page 490 40.3 Muscular Dysfunction Associated with Se Deficiencies in Livestock......Page 491 40.4 Muscular Dysfunction Associated with Selenium Deficiencies in Humans......Page 492 40.5 Selenoproteins and Congenital Muscle Disorders......Page 493 40.6 SEPN1-Related Myopathy Pathophysiology: Translational Research and Therapeutic Implications......Page 494 40.7 Selenoprotein N Expression, Phylogeny and Predicted Functions......Page 496 References......Page 498 41.1 Introduction......Page 501 41.2 Deiodinases Are Integral Membrane Selenoproteins Containing a Thioredoxin- (TRX)-Fold that Are Regenerated by a Peroxiredoxin-Like Mechanism......Page 502 41.3 SECISBP2 Mutations Result in Altered Deiodination and Thyroid Hormone Profiles......Page 504 41.4 Local Control of Thyroid Hormone Concentrations by DIO2 and DIO3 Is Critical for Tissue Specific Regulation of Thyroid Hormone Action......Page 505 41.5 DIO2 and DIO3 Play Key Roles in Skeletal Muscle Regeneration During Injury......Page 507 References......Page 510 Chapter 42: The Role of Selenoproteins in Resolution of Inflammation......Page 513 42.1 Overview of Inflammation and Its Resolution......Page 514 42.2 Modulation of Arachidonic Acid Metabolism in Macrophages by Se......Page 515 42.3 Resolution of Gastrointestinal Inflammation During Helminth Infection......Page 516 42.4 Macrophage Regulation of Inflammation and Resolution in Leukemia......Page 519 42.5 Selenium and Selenoproteins Maintain Redox Status in Erythropoiesis......Page 521 42.6 Concluding Remarks......Page 522 References......Page 523 43.1 Introduction......Page 525 43.2 Gpx4: Beyond Apoptosis......Page 527 43.3 In Vivo Relevance of Ferroptosis......Page 531 References......Page 534 44.1 Introduction......Page 536 44.2 Human SECISBP2 Mutations......Page 537 44.3 TRU-TCA1-1 Mutation......Page 545 44.4 SEPSECS Mutations......Page 547 44.5 Concluding Remarks......Page 549 References......Page 550 Chapter 45: Alteration of Selenoprotein Expression During Stress and in Aging......Page 552 45.2.1.2 Longevity......Page 553 45.2.1.6 Reactive Nitrogen Species (RNS)......Page 554 45.2.3 Damage Theory of Aging......Page 555 45.3.1 Mechanism and Factors for Sec Insertion......Page 556 45.3.2 Translational Control of Selenoproteins......Page 558 45.3.3 Transcriptional Control of Selenoproteins......Page 559 45.4.1 Oxidative Stress......Page 560 45.5 Concluding Remarks......Page 561 References......Page 563 Part V: Biological Models for Elucidating the Role of Selenium and Selenoproteins in Biology and Medicine......Page 565 46.1 Introduction......Page 566 46.2 Transfer RNA[Ser]Sec Mouse Models to Elucidate Selenoprotein Function......Page 567 46.2.1 Mouse Models Involving only Trsp Transgenes......Page 568 46.2.2 Mouse Models Involving Trsp Knockout and Trsp Conditional Knockout Mice......Page 569 46.2.3 TrspΔ and TrspcΔ Mice Complemented with Transgenes......Page 573 46.3 Concluding Remarks......Page 575 References......Page 576 47.1 Introduction......Page 578 47.2 Studies On Mice With Mutations Interfering with General Selenoprotein Synthesis......Page 579 47.3 Glutathione Peroxidases......Page 581 47.4 Thioredoxin Reductases......Page 583 47.5 Deiodinases......Page 584 47.6 Other Selenoproteins......Page 585 47.7 Concluding Remarks......Page 586 References......Page 587 48.1 Introduction......Page 590 48.2.2 Resistance to Cancer......Page 591 48.2.5 Eusociality......Page 592 48.2.6 Hypoxia Tolerance......Page 593 48.4 Ionome and Selenoproteome......Page 594 48.6 Concluding Remarks......Page 595 References......Page 596 49.1 Introduction......Page 597 49.2 Gpx1 Transgenic Mouse Model......Page 598 49.3 Gpx1 Knockout Model......Page 599 49.4 Human Health Relevance of GPX1-Related Metabolic Disorders......Page 601 49.5 Concluding Remarks......Page 602 References......Page 603 50.1 Introduction......Page 605 50.2.1 Breeders......Page 606 50.2.3 Broilers......Page 607 50.3.1 Se for Swine Breeders: Boars and Sows......Page 608 50.3.2 Se in Newborn Piglets......Page 609 50.4 Se in Ruminant Nutrition......Page 610 50.5.1 Horses......Page 611 50.6 Organic Se Concept in Animal Nutrition......Page 612 50.7 Organic Se Sources: a Re-evaluation......Page 613 References......Page 615 Index......Page 617 In The Current Edition, Selenium: Its Molecular Biology And Role In Human Health Expands Extensively On The Previous Editions Providing Readers With The Most Significant Advances In The Rapidly Developing Selenium Field. Evidence From Epidemiology And Veterinary Science Supports The Essential Role Of Selenium In (human) Health, But Its Split Personality In Both Preventing And Supporting Cancer And Also In Promoting Insulin Resistance Has Become More Clearly Defined. The Pivotal Role Of Glutathione Peroxidase 4 In A New Process Of Programmed Cell Death, Ferroptosis, Brings New Impetus To The Field. Recently Defined Mutations In Selenoprotein And Biosynthesis Factor Genes Have Been Identified In Patients, And The Resulting Disorders Further Emphasize The Significance Of Selenoproteins In Human Health. The Mechanism Of Selenoprotein Biosynthesis, The Functions Of Selenoproteins, And The Roles Of Dietary Selenium Have Been Further Elucidated, And New Regulatory Mechanisms Involving Selenoproteins Discovered. The Book, Therefore, Covers The Breadth Of Current Selenium Research. With Up-to-date Chapters Written By Leaders In Their Fields, It Serves As An Invaluable Resource For Novices As Well As Specialists. Part I. The Machinery Of Selenoprotein Biosynthesis -- 1 Selenocysteine Trna[ser]sec: From Nonsense Suppressor Trna To The Quintessential Constituent In Selenoprotein Biosynthesis -- 2 Eukaryotic Mechanisms Of Selenocysteine Translation And Its Reconstitution In Vitro -- 3 Probing Selenoprotein Translation By Ribosome Profiling -- 4 Pathways In De Novo Biosynthesis Of Selenocysteine And Cysteine In Eukaryotes -- 5 Prokaryotic Selenoprotein Biosynthesis And Function -- 6 The Role Of Selenium In Human Evolution -- 7 The Chemistry Of Selenocysteine In Proteins -- 8 Evolution Of Selenophosphate Synthetase -- 9 Structure And Mechanism Of Selenocysteine Synthases. 10 Mechanism, Structure, And Biological Role Of Selenocysteine Lyase -- Part Ii. Selenoproteins, Their Occurrence And Function -- 11 Eukaryotic Selenoproteomes -- 12 Prokaryotic Selenoproteins And Selenoproteomes -- 13 Functional Genomics Of Selenoproteins And Se-responsive Pathways -- 14 Selenium Regulation Of The Selenoprotein And Non-selenoprotein Transcriptomes In A Variety Of Species -- 15 77se Nmr Spectroscopy Of Selenoproteins -- 16 Thioredoxin Reductase 1 As An Anticancer Drug Target -- 17 Basics And News On Glutathione Peroxidases -- 18 Glutathione Peroxidase 4 -- 19 The 15 Kda Selenoprotein: Insights Into Its Regulation And Function. 20 Selenoprotein K And Protein Palmitoylation In Regulating Immune Cell Functions -- 21 Selenoprotein M: Structure, Expression And Functional Relevance -- 22 Selenoprotein P And Selenium Distribution In Mammals -- 23 Selenoprotein T: From Discovery To Functional Studies Using Conditional Knockout Mice -- 24 Biochemistry And Function Of Methionine Sulfoxide Reductase -- Part Iii. Dietary Selenium And Its Impact On Human Health -- 25 Selenium: Dietary Sources, Human Nutritional Requirements And Intake Across Populations -- 26 Human Clinical Trials Involving Selenium -- 27 Status Of Dietary Selenium In Cancer Prevention -- 28 Selenium In Hiv/aids. 29 Genetic Variations In The Genes For Selenoproteins Implicate The Encoded Proteins In Cancer Etiology -- 30 Is Adequate Selenium Important For Healthy Human Pregnancy? -- 31 The Epidemiology Of Selenium And Human Health -- 32 Sex-specific Differences In Biological Effects And Metabolism Of Selenium -- 33 Selenium And Endocrine Tissues -- 34 Selenium Antagonism With Mercury And Arsenic: From Chemistry To Population Health And Demography -- 35 Biological Selenium Species And Selenium Speciation In Biological Samples -- 36 Selenoproteins In Nervous System Development, Function And Degeneration -- 37 Interplay Of Selenoproteins And Different Antioxidant Systems In Various Cancers. 38 Glutathione Peroxidase 2, A Selenoprotein Exhibiting A Dual Personality In Preventing And Promoting Cancer -- 39 Selenoproteins In Cardiovascular Redox Pathology -- 40 What Do We Know About Selenium Contributions To Muscle Physiology? -- 41 Tissue-specific Regulation Of Thyroid Status By Selenodeiodinases -- 42 The Role Of Selenoproteins In Resolution Of Inflammation -- 43 Glutathione Peroxidase 4 And Ferroptosis -- 44 Mutations In Humans That Adversely Affect The Selenoprotein Synthesis Pathway -- 45 Alteration Of Selenoprotein Expression During Stress And In Aging -- Part V. Biological Models For Elucidating The Role Of Selenium And Selenoproteins In Biology And Medicine. 46 Selenocysteine Trna[ser]sec Mouse Models For Elucidating Roles Of Selenoproteins In Health And Development -- 47 Mouse Models That Target Individual Selenoproteins -- 48 The Naked Mole Rat And Selenium -- 49 Glutathione Peroxidase 1: Models For Diabetes And Obesity -- 50 Selenium In Livestock And Other Domestic Animals. Dolph L. Hatfield, Ulrich Schweizer, Petra A. Tsuji, Vadim N. Gladyshev, Editors. Includes Bibliographical References And Index. As discussed in this book, a large body of evidence indicates that selenium is a cancer chemopreventive agent. Further evidence points to a role of this element in reducing viral expression, in preventing heart disease, and other cardiovascular and muscle disorders, and in delaying the progression of AIDS in HIV infected patients. Selenium may also have a role in mammalian development, in male fertility, in immune function and in slowing the aging process. The mechanism by which selenium exerts its beneficial effects on health may be through selenium-containing proteins. Selenium is incorporated into protein as the amino acid selenocysteine. Selenocysteine utilizes a specific tRNA, a specific elongation factor, a specific set of signals, and the codeword, UGA, for its cotranslational insertion into protein. It is indeed the 21st naturally occurring amino acid to be incorporated into protein and marks the first and only expansion of the genetic code since the code was deciphered in the mid 1960s.