The Collagens: Biochemistry and Pathophysiology

1 Introduction: Historical Outline.- 2 Structure, Heterogeneity, and Distribution.- 2.1 Basic Nomenclature.- 2.2 Triple-Chain Helical Structure.- 2.3 Distribution.- 2.4 Classification and General Structural Features of the Collagens.- 2.5 Type I, Type II, Type III Collagens, and Type I-Trimer Collagen.- 2.6 Type IV Collagen.- 2.7 Type V Collagen.- 2.8 Type VI Collagen.- 2.9 Type VII Collagen.- 2.10 Type VIII Collagen.- 2.11 Type IX Collagen.- 2.12 Type X Collagen.- 2.13 Type XI Collagen.- 2.14 Type XII Collagen.- 2.15 Type XIII Collagen.- 2.16 Proteins Containing a Collagenlike Sequence.- 2.16.1 Acetylcholinesterase.- 2.16.2 Mammalian Lectins.- 2.16.2.1 Complement Component C1q.- 2.16.2.2 Conglutinin.- 2.16.2.3 Mannan-Binding Protein.- 2.16.2.4 Lung Surfactant Protein.- 3 Biosynthesis of Collagen.- 3.1 Introduction.- 3.2 Procollagen Genes.- 3.3 Cleavage of the Signal Peptide.- 3.4 Hydroxylation of Proline and Lysine Residues.- 3.5 Glycosylation of Hydroxylysine Residues.- 3.6 Glycosylation of Asparagine Residues.- 3.7 Chain Association, Disulfide Bonding, and Formation of the Helical Structure.- 3.8 Conversion of Procollagen to Collagen.- 3.9 Formation of the Supramolecular Structures.- 3.10 Cross-Linking of Collagen.- 3.11 Interaction of Collagen with Components of the Extracellular Matrix.- 3.11.1 General Remarks.- 3.11.2 Collagen-Proteoglycan Interactions.- 3.11.3 Structural Glycoproteins.- 3.11.3.1 Fibronectin.- 3.11.3.2 Laminin.- 3.11.3.3 Entactin and Nitogen.- 3.11.3.4 Chondrionectin.- 3.11.3.5 Fibromodulin.- 4 Degradation.- 4.1 Introduction.- 4.2 General Pathways of Collagen Degradation.- 4.3 Depolymerization.- 4.4 Tissue Collagenases.- 4.5 Collagenolytic Cathepsins.- 4.6 Gelatinases and Collagen Peptidase.- 4.7 Collagenolytic Enzymes of Microbial Origin.- 5 Turnover and Regulation of Collagen Metabolism.- 5.1 Introduction.- 5.2 Transcriptional and Translational Control of Collagen Synthesis.- 5.3 Regulation of Collagen Synthesis at the Intracellular Posttranslational Level.- 5.4 Intracellular Degradation of Procollagen.- 5.5 Feedback Inhibition of Biosynthesis of Collagen by Aminoterminal Propeptides.- 5.6 Role of the Free Proline Pool in the Regulation of Collagen Synthesis.- 5.7 Turnover of Collagen.- 6 Collagen in Development, Aging, and Phylogeny.- 6.1 Collagen and Development.- 6.2 Collagen and Aging.- 6.3 Phylogenetic Aspects of Collagen.- 6.3.1 Collagen and Animal Phylogeny.- 6.3.2 Plants and Unicellular Organisms.- 6.3.3 Porifera.- 6.3.4 Coelenterata.- 6.3.5 Platyhelmintha.- 6.3.6 Aschelminthes.- 6.3.7 Annelida.- 6.3.8 Arthropoda.- 6.3.9 Mollusca.- 6.3.10 Echinodermata.- 6.3.11 Chordata.- 7 Hormonal Regulation of Collagen Metabolism.- 7.1 Introduction.- 7.2 Thyroxine, Triiodothyronine, and Thyrotropic Hormone.- 7.3 Glucocorticoids.- 7.4 Growth Hormone.- 7.5 Insulin and Glucagon.- 7.6 Prolactin.- 7.7 Histamine.- 8 Immunobiology of Collagen.- 8.1 Introduction.- 8.2 Antigenicity of Collagen and Procollagen.- 8.3 Immune Response to Collagens and Procollagens.- 8.4 Effect of Cytokines on Collagen Metabolism.- 9 Hereditary Disorders of Collagen.- 9.1 Introduction.- 9.2 The Ehlers-Danlos Syndrome.- 9.3 The Marfan Syndrome.- 9.4 Osteogenesis Imperfecta.- 9.4.1 Osteogenesis Imperfecta Type I.- 9.4.2 Osteogenesis Imperfecta Type II.- 9.4.3 Osteogenesis Imperfecta Type III.- 9.4.4 Osteogenesis Imperfecta Type IV.- 9.5 Epidermolysis Bullosa.- 9.6 Chondrodysplasias.- 9.7 Congenital Dislocation of the Hip.- 9.8 The Nail-Patella Syndrome.- 9.9 Hereditary Progressive Glomerulopathy (Alport's Syndrome).- 9.10 Homocystinuria.- 9.11Alkaptonuria.- 9.12 Aspartylglycosaminuria.- 9.13 Familial Cutaneous Collagenoma.- 9.14 Focal Dermal Hypoplasia.- 9.15 Hyalinosis Cutis et Mucosae.- 9.16 Fibrodysplasia Ossificans Progressiva.- 9.17 Hereditary Disorders of Collagen Metabolism in Animals.- 10 Collagen Diseases.- 10.1 Introduction.- 10.2 Scleroderma and Related Conditions.- 10.3 Other Collagen Diseases.- 10.4 Drug-Induced Lupus-Like Syndrome.- 11 Musculoskeletal System.- 11.1 Introduction.- 11.2 Bone.- 11.2.1 Structure and Function.- 11.2.2 Collagen in Bone.- 11.2.3 Collagen in Pathology of Bone.- 11.2.3.1 Disturbed Regulation of Calcium and Phosphorus Metabolism.- 11.2.3.2 Osteoporosis.- 11.2.3.3 Paget's Disease.- 11.3 Cartilage.- 11.3.1 Structure and Function.- 11.3.2 Collagens of the Cartilage.- 11.4 Intervertebral Disc.- 11.4.1 Structure and Function.- 11.4.2 Collagen in the Intervertebral Disc.- 11.4.3 Collagen in Pathology of the Intervertebral Disc.- 11.4.3.1 Age-Related Degeneration.- 11.4.3.2 Chemonucleolysis.- 11.4.3.3 Scoliosis.- 11.5 Tendons and Related Structures.- 11.5.1 Structure and Function.- 11.5.2 Collagen in Tendinous Pathology.- 11.5.2.1 Dupuytren's Contracture.- 11.5.2.2 Carpal Tunnel Syndrome.- 11.6 Joints.- 11.6.1 Role of Collagen in the Structure and Function.- 11.7 Skeletal Muscle.- 11.7.1 Role of Collagen in the Structure and Function.- 11.7.2 Collagen in the Pathology.- 11.8 Collagen in Rheumatic Disorders.- 11.8.1 Rheumatoid Arthritis.- 11.8.2 Osteoarthrosis.- 11.8.3 Animal Models of Rheumatic Disorders.- 12 Cardiovascular System.- 12.1 Introduction.- 12.2 The Heart.- 12.2.1 General Structural Features.- 12.2.2 Collagen in the Normal Heart Muscle.- 12.2.3 Collagen in Myocardial Hypertrophy.- 12.2.4 Collagen in Myocardial Infarction.- 12.2.5 Collagen in the Valves inHealth and Disease.- 12.3 Vessels.- 12.3.1 General Characteristics.- 12.3.2 Collagen in the Normal Vessel Wall.- 12.3.3 Atherosclerosis.- 12.3.4 Hypertension.- 13 Respiratory System.- 13.1 General Structural Features.- 13.2 Collagen Content in the Lungs.- 13.3 Cells Involved in Collagen Production.- 13.4 Collagen and Lung Disease.- 13.4.1 Introduction.- 13.4.2 Fibrotic Lung Disorders.- 13.4.3 Destructive Lung Disorders.- 14 The Liver.- 14.1 Introduction.- 14.2 Collagen Content in the Liver.- 14.3 Collagen Synthesizing Cells.- 14.4 Fibrosis as a Response of the Liver Bioecosystem.- 14.5 Collagen Content in the Fibrotic Liver.- 14.6 Metabolism of Collagen in the Liver.- 14.7 Regulation of Collagen Metabolism and Development of Fibrosis.- 14.8 Collagen in Liver Regeneration.- 14.9 Collagen Metabolism in Diseases of the Bile Ducts.- 14.10 Indices of Collagen Metabolism in Hepatic Disorders.- 15 The Teeth and Periodontal Tissues.- 15.1 Structure and Collagen Content in Normal Teeth.- 15.1.1 Dentin.- 15.1.2 Cementum.- 15.1.3 Enamel.- 15.1.4 Dental Pulp.- 15.1.5 Periodontium.- 15.2 The Role of Collagen in Development of Teeth.- 15.3 Collagen and Dental and Periodontal Pathology.- 15.3.1 Periodontal Disease.- 15.3.2 Hydantoin-Induced Gingival Hyperplasia.- 16 The Skin and Wound Healing.- 16.1 Collagen in the Skin.- 16.2 Collagen in Cutaneous Diseases.- 16.3 Collagen in Keloids.- 16.4 Wound Healing.- 17 The Eye and The Ear.- 17.1 The Eye.- 17.1.1 General Structural Features.- 17.1.2 The Cornea and the Sclera.- 17.1.3 The Uvea.- 17.1.4 The Lens.- 17.1.5 The Vitreous Body.- 17.1.6 The Retina.- 17.1.7 Collagen in Ocular Pathology.- 17.2 The Ear.- 18 Urinary and Reproductive Systems.- 18.1 Introduction.- 18.2 The Urinary System.- 18.3 The Ovary.- 18.4 The Uterus and Pregnancy.- 18.5 Placenta.- 19 Collagen in the Nervous System.- 20 Collagen in Hematology.- 20.1 Collagen and Hematostasis.- 20.2 Collagen in the Bone Marrow.- 20.3 Collagen in the Lymph Nodes.- 21 Collagen and Neoplasia.- 21.1 Introduction.- 21.2 Collagen in the Stroma of Neoplasms.- 21.3 Collagenolysis and Tumor Invasion.- 22 Effect of Nutrition.- 22.1 Malnutrition and Overnutrition.- 22.2 Scurvy.- 23 Effect of Ionizing Radiation.- 24 Pharmacological Control of Collagen Metabolism.- 24.1 Introduction.- 24.2 Direct Inhibitors of Collagen Synthesis.- 24.2.1 Pharmacological Control of Hydroxylation of Proline and Lysine Residues.- 24.2.1.1 Structural Analogues of Proline.- 24.2.1.2 Cosubstrates and Cofactors of Hydroxylation.- 24.2.1.3 Fibrostatins.- 24.2.2 Pharmacological Control of Collagen Secretion.- 24.2.3 Pharmacological Control of the Conversion of Procollagen to Collagen.- 24.2.4 Pharmacological Control of Extracellular Processing of Collagen.- 24.2.4.1 Lathyrism.- 24.2.4.2 Penicillamine.- 24 2 4 3 Inhibitors of Lysyl Oxidase with Respect to Pyridoxal.- 24.2.5 Antifibroblast Serum.- 24.3 Pharmacological Control of Collagen Degradation.- 24.3.1 Induction of Collagenolysis.- 24.3.2 Inhibitors of Collagenase Secretion.- 24.3.3 Inhibitors of Mammalian Collagenases.- 24.4 Drugs That Indirectly Affect Collagen Metabolism.- 24.4.1 Nonsteroidal Antiinflammatory Drugs.- 24.4.2 Tissue Extracts.- 24.4.3 Heavy Metals.- 24.4.4 Fluoride.- 24.4.5 Cytostatic Drugs.- 24.4.6 Immunomodulants.- 24.4.7 Antibiotics.- 25 Indices of Collagen Metabolism in Clinical Practice.- References.