Transthyretin from Discovery to Now
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Jacob Robbins
Abstract
As introduction to the First International Congress on Transthyretin in Health and Disease, this lecture traces the origin of the subject from the discovery in the 1950s that a serum protein migrating ahead of albumin in an electrical field binds the thyroid hormone, thyroxine. Early work defined the molecular and biological properties of thyroxine-binding prealbumin (TBPA). Its tetrameric structure, first recognized from a polymorphism in monkeys, was later elaborated by crystallographic studies, and the very different affinity of its two identical thyroxine-binding sites was explained by an allosteric effect upon occupation of the first site. The far higher concentration of TBPA in cerebrospinal fluid compared to blood was explained by the discovery, 30 years later, that TBPA is synthesized by cells of the choroid plexus, and its rapid turnover in the body made TBPA a convenient marker of malnutrition and chronic disease. Late in the 1960s it was learned that TBPA also carries vitamin A in the circulation by interacting with retinol-binding protein (RBP). TBPA then was renamed transthyretin (TTR), in recognition of its dual transport function, and it was shown that retinol-RBP-TTR interactions are mutually enhancing. Investigation of the molecular genetics of TTR began in 1980 and a large number of inherited variants were discovered in the ensuing years. Some affect thyroxine and/or RBP binding but the majority are associated with familial amyloidotic polyneuropathy. Seizing on this discovery, structural biologists are now investigating why mutated TTR changes from a compact, soluble molecule into a fibrillar, insoluble polymer, and how this pathological transformation might be prevented.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Author Index
- Subject Index
- Contents
- Historical Aspects and Perspectives in Transthyretin Research
- Transthyretin from Discovery to Now
- The Evolution of Transthyretin Synthesis in Vertebrate Liver, in Primitive Eukaryotes and in Bacteria
- The Evolution of Transthyretin Synthesis in the Choroid Plexus
- Hepatic Synthesis, Maturation and Complex Formation between Retinol-Binding Protein and Transthyretin
- Synthesis and Structural Analysis of the N-Terminal Domain of the Thyroid Hormone-Binding Protein Transthyretin
- Three-Dimensional Structure of the Transthyretin-Retinol-Binding Protein Complex
- Mechanisms of Molecular Recognition: Crystal Structure Analysis of Human and Rat Transthyretin Inhibitor Complexes
- Transthyretin in Fish: State of the Art
- The Effects of Endocrine-Disrupting Chemicals on Thyroid Hormone Binding to Xenopus laevis Transthyretin and Thyroid Hormone Receptor
- Clinical Picture and Outcome of Transthyretin-Related Familial Amyloid Polyneuropathy (FAP) in Japanese Patients
- Laboratory Assessment of Transthyretin Amyloidosis
- Amyloid: Morphology and Toxicity
- Historical Overview of Analytical Methods for the Measurement of Transthyretin
- Nutritional Regulation of Visceral Markers in Rat Liver and Cultured Hepatoma Cells
- Significance of Transthyretin in Protein Metabolism
- Transthyretin as a Thyroid Hormone Carrier: Function Revisited
- The Molar Ratio of Retinol-Binding Protein to Transthyretin in the Assessment of Vitamin A Status in Adults. Proposal of a Cut-off Point
- Observations with Regard to the National Kidney Foundation K/DOQI Clinical Practice Guidelines Concerning Serum Transthyretin in Chronic Renal Failure
- Metabolism and Clinical Interest of Serum Transthyretin (Prealbumin) in Dialysis Patients
- Protein Status in Pancreatitis – Transthyretin Is a Sensitive Biomarker of Malnutrition in Acute and Chronic Pancreatitis
- Assessment of Nutritional Status in Organ Transplant: Is Transthyretin a Reliable Indicator?
- Body Composition and Nutritional Parameters in HIV and AIDS Patients
- C-Reactive Protein to Transthyretin Ratio for the Early Diagnosis and Follow-up of Postoperative Infection
- The Prognostic Value of Nutritional and Inflammatory Indices in Critically Ill Patients with Acute Respiratory Failure
- Transthyretin: Its Response to Malnutrition and Stress Injury. Clinical Usefulness and Economic Implications
- Transthyretin Measurement as a Screening Tool for Protein Calorie Malnutrition in Emergency Hospital Admissions
- Outcomes of Continuous Process Improvement of a Nutritional Care Program Incorporating TTR Measurement
- The Role of Visceral Protein Markers in Protein Calorie Malnutrition
- Acknowledgement
- Meetings
Articles in the same Issue
- Author Index
- Subject Index
- Contents
- Historical Aspects and Perspectives in Transthyretin Research
- Transthyretin from Discovery to Now
- The Evolution of Transthyretin Synthesis in Vertebrate Liver, in Primitive Eukaryotes and in Bacteria
- The Evolution of Transthyretin Synthesis in the Choroid Plexus
- Hepatic Synthesis, Maturation and Complex Formation between Retinol-Binding Protein and Transthyretin
- Synthesis and Structural Analysis of the N-Terminal Domain of the Thyroid Hormone-Binding Protein Transthyretin
- Three-Dimensional Structure of the Transthyretin-Retinol-Binding Protein Complex
- Mechanisms of Molecular Recognition: Crystal Structure Analysis of Human and Rat Transthyretin Inhibitor Complexes
- Transthyretin in Fish: State of the Art
- The Effects of Endocrine-Disrupting Chemicals on Thyroid Hormone Binding to Xenopus laevis Transthyretin and Thyroid Hormone Receptor
- Clinical Picture and Outcome of Transthyretin-Related Familial Amyloid Polyneuropathy (FAP) in Japanese Patients
- Laboratory Assessment of Transthyretin Amyloidosis
- Amyloid: Morphology and Toxicity
- Historical Overview of Analytical Methods for the Measurement of Transthyretin
- Nutritional Regulation of Visceral Markers in Rat Liver and Cultured Hepatoma Cells
- Significance of Transthyretin in Protein Metabolism
- Transthyretin as a Thyroid Hormone Carrier: Function Revisited
- The Molar Ratio of Retinol-Binding Protein to Transthyretin in the Assessment of Vitamin A Status in Adults. Proposal of a Cut-off Point
- Observations with Regard to the National Kidney Foundation K/DOQI Clinical Practice Guidelines Concerning Serum Transthyretin in Chronic Renal Failure
- Metabolism and Clinical Interest of Serum Transthyretin (Prealbumin) in Dialysis Patients
- Protein Status in Pancreatitis – Transthyretin Is a Sensitive Biomarker of Malnutrition in Acute and Chronic Pancreatitis
- Assessment of Nutritional Status in Organ Transplant: Is Transthyretin a Reliable Indicator?
- Body Composition and Nutritional Parameters in HIV and AIDS Patients
- C-Reactive Protein to Transthyretin Ratio for the Early Diagnosis and Follow-up of Postoperative Infection
- The Prognostic Value of Nutritional and Inflammatory Indices in Critically Ill Patients with Acute Respiratory Failure
- Transthyretin: Its Response to Malnutrition and Stress Injury. Clinical Usefulness and Economic Implications
- Transthyretin Measurement as a Screening Tool for Protein Calorie Malnutrition in Emergency Hospital Admissions
- Outcomes of Continuous Process Improvement of a Nutritional Care Program Incorporating TTR Measurement
- The Role of Visceral Protein Markers in Protein Calorie Malnutrition
- Acknowledgement
- Meetings
