pituitrin and Metabolism--Inborn-Errors

Topics: Adrenal Cortex Hormones; Adrenal Gland Diseases; Adrenal Hyperplasia, Congenital; Child; Dwarfism, Pituitary; Endocrine System Diseases; Humans; Metabolism, Inborn Errors; Mixed Function Oxygenases; Pedigree; Pituitary Hormones, Anterior; Thyroid Diseases; Thyroid Hormones; Vasopressins

A transition of G to A at nucleotide position 279 in exon 1 of the vasopressin gene has been identified in patients with familial central diabetes insipidus. The mutation predicts an amino acid substitution of Thr (ACG) for Ala (GCG) at the COOH terminus of the signal peptide in preprovasopression (preproVP). Translation in vitro of wild-type and mutant mRNAs produced 19-kD preproVPs. When translated in the presence of canine pancreatic rough microsomes, wild-type preproVP was converted to a 21-kD protein, whereas the mutant mRNA produced proteins of 21 kD and 23 kD. NH2-terminal amino acid sequence analysis revealed that the 21-kD proteins from the wild-type and the mutants were proVPs generated by the proteolytic cleavage of the 19-residue signal peptide and the addition of carbohydrate. Accordingly, mutant preproVP was cleaved at the correct site after Thr-19, but the efficiency of cleavage by signal peptidase was < 25% that observed for the wild-type preproVP, resulting in the formation of a predominant glycosylated but uncleaved 23-kD product. These data suggest that inefficient processing of preproVP produced by the mutant allele is possibly involved in the pathogenesis of diabetes insipidus in the affected individuals.

Topics: Amino Acid Sequence; Amino Acids; Asian People; Base Sequence; Cloning, Molecular; Diabetes Insipidus; Endopeptidases; Exons; Female; Genome; Humans; Japan; Male; Membrane Proteins; Metabolism, Inborn Errors; Molecular Sequence Data; Mutation; Pedigree; Protein Biosynthesis; Protein Precursors; Protein Sorting Signals; RNA, Messenger; Sequence Analysis, DNA; Serine Endopeptidases; Transcription, Genetic; Vasopressins

Topics: Amino Acid Metabolism, Inborn Errors; Aspartic Acid; Bipolar Disorder; Catatonia; Circadian Rhythm; Cysteine; Humans; Intellectual Disability; Lithium; Mass Spectrometry; Mental Disorders; Metabolism, Inborn Errors; Periodicity; Phenylketonurias; Sleep; Vasopressins

Topics: Adenosine Triphosphate; Age Factors; Cell Division; Cells, Cultured; Cybernetics; Ethanol; Glucose; Glucose Oxidase; Glycolysis; Metabolism, Inborn Errors; Models, Biological; Mutation; Oxygen Consumption; Saccharomyces; Saccharomyces cerevisiae; Vasopressins

Topics: Analysis of Variance; Animals; Diabetes Insipidus; Female; Heterozygote; Hypothalamo-Hypophyseal System; Male; Metabolism, Inborn Errors; Osmolar Concentration; Pituitary Gland, Posterior; Plasma; Rats; Urine; Vasopressins; Water Deprivation

Topics: Animals; Biological Assay; Diabetes Insipidus; Female; Hypothalamus; In Vitro Techniques; Metabolism, Inborn Errors; Muscle, Smooth; Oxytocin; Pituitary Gland, Posterior; Rats; Rodent Diseases; Urine; Uterus; Vasopressins; Water-Electrolyte Balance