Principles of Applied Clinical Chemistry

A Plasma Protein Properties and Metabolism.- Section I. Nature of the Plasma Proteins.- 1 Introduction.- 1.1 Historical Background.- 1.2 Selected Reading.- 1.3 References.- 2 Protein Composition and Properties.- 2.1 Chemical Composition of Proteins.- 2.2 Primary, Secondary, Tertiary, and Quaternary Structure.- 2.3 Proteins in Solution.- 2.4 Recapitulation.- 2.5 Selected Reading.- 3 Plasma Protein Survey.- 3.1 Classification.- 3.2 Protein Fractionation.- 3.2.1 The Serum Electrophoretic Pattern.- 3.2.2 Moving-Boundary Electrophoresis.- 3.2.3 Zone Electrophoresis.- 3.2.4 The Ultracentrifuge.- 3.3 References.- Section II. Plasma Protein Metabolism.- 4 Albumin in Nutrition and Transport.- 4.1 Physical and Chemical Properties of Albumin.- 4.2 Microheterogeneity of Serum Albumin.- 4.3 Normal Distribution and Origin.- 4.4 Albumin Function in the Healthy Human.- 4.4.1 Albumin as a Transport Protein.- 4.4.2 Albumin in Nutrition and Osmotic Regulation.- 4.4.2.1 Hormonal Effects on Albumin Synthesis.- 4.4.2.2 Albumin in Cell Nutrition.- 4.5 Albumin Variants.- 4.5.1 Bisalbuminemia.- 4.5.2 Analbuminemia.- 4.6 Serum Albumin Changes in Disease.- 4.7 I.V. Albumin Therapy.- 4.8 Serum Albumin Assay.- 4.9 Recapitulation.- 4.10 Selected Reading.- 4.11 References.- 5 Glycoproteins and Proteoglycans.- 5.1 Isolation of the Plasma Glycoproteins.- 5.2 The Nature of the Carbohydrate Protein Linkage.- 5.3 Studies of the Structure of the Heterosaccharides.- 5.4 Heterosaccharide Synthesis.- 5.5 Glycoprotein Heterosaccharide Structure.- 5.5.1 Heterosaccharide Structure of the Blood Group Glycoproteins.- 5.5.2 Mucin Heterosaccharides.- 5.5.3 Collagen Heterosaccharides.- 5.6 Function of the Oligosaccharides of Glycoproteins.- 5.7 Acute-Phase Reactants.- 5.7.1 C-Reactive Protein.- 5.7.2 ?l Acid Glycoprotein.- 5.7.3 Low-Concentration Acute-Phase Glycoproteins.- 5.7.3.1 Pregnancy-Associated Glycoprotein.- 5.7.3.2 Zinc-?2 Glycoprotein.- 5.7.3.3 Seromucoid Proteins.- 5.8 Glycoprotein Catabolism.- 5.8.1 Abnormal Glycoprotein Catabolism.- 5.8.2 Mannosidosis.- 5.8.3 Fucosidosis.- 5.9 Glycosaminoglycans: The Mucopolysaccharides.- 5.10 Genetic Glycosaminoglycan Storage Diseases.- 5.10.1 Hurler’s Syndrome (Type I H).- 5.10.2 Scheie’s Syndrome (Type I S).- 5.10.3 Hunter’s Syndrome (Type II).- 5.10.4 Sanfilippo Syndromes A and B (Type III).- 5.10.5 Morquio’s Syndrome (Type IV).- 5.10.6 Maroteaux—Lamy Syndrome (Type VI).- 5.10.7 Sly Syndrome: ?-Glucuronidase Deficiency (Type VII).- 5.10.8 Glycosaminoglycan Lysosomal Storage Diseases.- 5.10.8.1 Aspartylglucosaminuria.- 5.10.8.2 The Mucolipidoses (ML): Neuraminidase Deficiency.- 5.11 Proteoglycans.- 5.11.1 Proteoglycan Aggregates.- 5.11.2 Proteoglycan Synthesis.- 5.11.3 Function of Proteoglycans in Health and Disease.- 5.12 Recapitulation.- 5.13 Selected Reading.- 5.14 References.- 6 Lipoproteins in Nutrition and Transport.- 6.1 Plasma Lipids: Composition.- 6.1.1 Serum Cholesterol.- 6.1.2 Plasma Free Fatty Acids.- 6.1.3 Neutral Plasma Glycerides.- 6.1.4 Phospholipids.- 6.2 Lipoproteins.- 6.2.1 The Major Lipoprotein Groups.- 6.2.2 Composition of the Lipoprotein Classes.- 6.2.3 The Apolipoproteins.- 6.2.3.1 Apolipoprotein A (apoA).- 6.2.3.2 Apolipoprotein B (apoB).- 6.2.3.3 Apolipoprotein C (apoC).- 6.2.3.4 Apolipoprotein D (apoD).- 6.2.3.5 Apolipoprotein E (apoE).- 6.2.3.6 Minor Apolipoproteins.- 6.3 Lipoprotein Formation.- 6.4 Normal Lipoprotein Metabolism.- 6.5 Abnormal Lipoprotein Metabolism.- 6.5.1 Genetic Defects in the Plasma Lipoproteins.- 6.5.2 Hypo- and A-?-lipoproteinemia.- 6.5.3 Hypo-?-lipoproteinemia, Tangier Disease.- 6.5.4 The Hyperlipoproteinemias.- 6.5.4.1 Familial Fat-Induced Hyperlipemia (Type I).- 6.5.4.2 Familial Hyper-?-lipoproteinemia (Type II).- 6.5.4.3 Mutations Affecting LDL Metabolism.- 6.5.4.4 Dys-?-lipoproteinemia, Broad-? Disease (Type III).- 6.5.4.5 Hyper-pre-?-lipoproteinemia (Type IV).- 6.5.4.6 Familial Mixed Hypertriglyceridemia, Type V Disease.- 6.5.4.7 The Hyperlipoproteinemia Types: Summary.- 6.5.5 Familial Lecithin-Cholesterol Acyltransferase (LCAT) Deficiency.- 6.6 Acquired Hyperlipemias.- 6.7 High-Density Lipoprotein; Hyper-?-lipoproteinemia.- 6.8 Hyperlipemia and Nutrition.- 6.9 Hypolipidemic Drugs.- 6.10 Lipid and Lipoprotein Assay.- 6.11 Recapitulation.- 6.12 Selected Reading.- 6.13 References.- B Plasma Proteins in Transport of Intermediates, Minerals, and Hormones.- Section III. Plasma Transport Proteins.- 7 Transferrin: Iron Metabolism.- 7.1 Transport Proteins.- 7.2 Transferrin.- 7.2.1 Transferrin Variants.- 7.2.2 Transferrin Function.- 7.2.3 Transferrin and Iron Metabolism.- 7.3 Ferritin and Iron Storage.- 7.4 Aberrant Iron Metabolism.- 7.4.1 Increased Iron Losses due to Hemorrhage.- 7.4.2 Inadequate Iron Intake and Nutrition.- 7.4.3 Defective Iron Reutilization.- 7.4.4 Congenital Atransferrinemia.- 7.4.5 Iron Overload.- 7.4.6 Hemochromatosis.- 7.4.7 Iron-Loading Anemias.- 7.4.8 Laboratory Findings with Aberrant Iron Metabolism.- 7.5 Management of the Patient with Abnormal Iron Metabolism.- 7.6 Assay for Transferrin and Iron.- 7.7 Recapitulation.- 7.8 Selected Reading.- 7.9 References.- 8 Ceruloplasmin: Copper Metabolism.- 8.1 Ceruloplasmin.- 8.2 Ceruloplasmin Copper.- 8.3 Preparation of Ceruloplasmin.- 8.4 Nature of the Ceruloplasmin Chain.- 8.5 Genetic Variants.- 8.6 Ceruloplasmin Function and the Tissue Oxidases.- 8.7 Ceruloplasmin and Copper in Disease.- 8.7.1 Copper Deficiency and Ceruloplasmin.- 8.7.2 Normal Copper Content in the Human.- 8.7.3 Copper Overload.- 8.7.4 Ceruloplasmin, Copper, and Liver Disease.- 8.7.5 Wilson’s Disease.- 8.7.6 Management of the Patient with Aberrant Copper Metabolism.- 8.8 Ceruloplasmin and Copper Assay.- 8.9 Recapitulation.- 8.10 Selected Reading.- 8.11 References.- 9 Haptoglobins: Hemoglobin Binding.- 9.1 Survey.- 9.2 Haptoglobin Composition.- 9.3 Haptoglobin Electrophoresis.- 9.4 Gene Frequency of the Haptoglobins.- 9.5 The Haptoglobin Chains.- 9.5.1 Haptoglobin ? Chains.- 9.5.2 Haptoglobin ? Chains.- 9.6 Haptoglobin Carbohydrate.- 9.7 Hemoglobin Binding to Haptoglobin.- 9.8 Haptoglobin Variants.- 9.9 Quantitative Haptoglobin Variants.- 9.10 Anhaptoglobinemia.- 9.11 Serum Haptoglobin Concentration.- 9.12 Haptoglobin Function.- 9.13 Medical Applications.- 9.14 Haptoglobin Assay.- 9.15 Recapitulation.- 9.16 Selected Reading.- 9.17 References.- 10 Hemopexin: Iron Recycling.- 10.1 Hemopexin (? Haptoglobin).- 10.2 Hemopexin Composition.- 10.3 Heme Binding to Hemopexin.- 10.4 Hemopexin Function.- 10.5 Serum Hemopexin.- 10.6 Hemopexin in Iron Reutilization.- 10.7 Serum Hemopexin in Disease.- 10.8 Hemopexin Preparation.- 10.9 Hemopexin Assay.- 10.10 Recapitulation.- 10.11 Selected Reading.- 10.12 References.- 11 Prealbumin I: Iodothyronine-Binding Proteins.- 11.1 Prealbumin.- 11.2 Thyroxine-Binding Proteins.- 11.3 Thyroxine-Binding Prealbumin (TBPA).- 11.4 Thyroxine-Binding Globulin (TBG).- 11.5 Plasma Thyroxine-Binding Proteins and Thyroid Function.- 11.6 Assay for Thyroid Function.- 11.7 Abnormal Serum TBG Levels.- 11.8 Recapitulation.- 11.9 Selected Reading.- 11.10 References.- 12 Prealbumin II: Vitamin A(Retinol)-Binding Protein.- 12.1 Retinol-Binding Protein.- 12.2 Retinol-Binding Protein and Vitamin A Transport.- 12.3 Retinol-Binding Protein in Disease.- 12.4 Retinol and Vision.- 12.5 Recapitulation.- 12.6 Selected Reading.- 12.7 References.- 13 Vitamin D Transport: Gc Globulins.- 13.1 Vitamin D and Hydroxy-Vitamin D.- 13.2 Group-Specific Component of Plasma, Gc Globulin.- 13.3 Gc Globulin Variants.- 13.4 Vitamin-D-Binding Protein and Disease.- 13.5 Recapitulation.- 13.6 Selected Reading.- 13.7 References.- 14 Steroid Hormone-Binding Proteins.- 14.1 Corticosteroid-Binding Globulin (CBG): Transcortin.- 14.2 Steroid Binding to Transcortin.- 14.3 Plasma Transcortin.- 14.4 Transcortin Plasma Concentration in Disease.- 14.5 Transcortin Function.- 14.6 Transcortin Assay.- 14.7 Recapitulation: Transcortin (CBG).- 14.8 Testosterone-Binding Globulin (TeBG).- 14.9 Characteristics of TeBG.- 14.10 Steroid Binding to TeBG.- 14.11 Plasma TeBG.- 14.11.1 Depressed Plasma TeBG Levels.- 14.11.2 Elevated TeBG Binding Capacity.- 14.12 Further Steroid Hormone-Binding Globulin Problems.- 14.13 Recapitulation: Testosterone-Binding Globulin.- 14.14 Selected Reading.- 14.15 References.- 15 Transcobalamins: Vitamin B12 Transport.- 15.1 Plasma Transcobalamins.- 15.2 Properties of the Transcobalamins.- 15.3 Transcobalamin Function.- 15.4 The Transcobalamins in Disease.- 15.5 Recapitulation.- 15.6 Selected Reading.- 15.7 References.- Section IV. Appendix.- A.1 Steroid Nomenclature.- A.1.1 Progesterone and the Corticosteroids.- A.1.2 The Steroid Sex Hormones.- A.1.3 The Bile Acids.- A.2 Mechanism of Cholesterol Formation.- A.3 Neutral and Phosphorylated Glyceride Structures.- A.3.1 Diglyceride Pathway for Glyceride Synthesis.- A.3.2 Monoglyceride Pathway for Glyceride Synthesis.- A.4 Nature of the Lipases.- A.4.1 Pancreatic Lipase.- A.4.2 Lipoprotein Lipase.- A.4.3 Hormone-Sensitive Lipase (HSL).- A.4.4 Other Tissue Lipases.- A.4.5 Phospholipases.- A.4.5.3 Lysophospholipase.- A.4.5.4 Phospholipase B.- A.4.5.5 Phospholipase C.- A.4.5.6 Phospholipase D.- A.5 Protein Parameters.- A.5.1 Absorptivity of the Plasma Proteins.- A.5.2 Partial Specific Volume of Proteins.- A.5.3 Viscosity and Frictional Resistance of Protein Molecules.- A.5.4 Plasma Protein Diffusion Coefficient.- A.5.5 Osmotic Pressure and Molecular Weight of Proteins.- A.5.6 Molecular Weight of Proteins by Diffusion.- A.5.7 Molecular Weight of Proteins by Sedimentation in the Ultracentrifuge.- A.5.8 Electrophoretic Mobility.- A.5.9 Selected Reading.