ABSTRACT
Charcot-Marie-Tooth (CMT) with autosomal recessive (AR) inheritance is a heterogeneous group of inherited motor and sensory neuropathies. Six genes and five additional loci have been identified that are responsible for either demyelinating or axonal forms of the disease. The gene encoding the ganglioside-induced-differentiation-associated protein 1 (GDAP1) has been associated with both demyelinating and axonal phenotypes. We report a detailed clinical, electrophysiological, and genetic study of two siblings from a Moroccan ARCMT family who are compound heterozygotes for the already described S194X and a new R310Q mutation in the GDAP1 gene. The electrophysiological data are compatible with an axonal form of the disease. The phenotype included hoarse voice and paralysis of the diaphragm. This study shows the variability of the phenotype associated with mutations in GDAP1 gene in terms of associated signs and severity.
Subject(s)
Charcot-Marie-Tooth Disease/genetics , Mutation , Nerve Tissue Proteins/genetics , Adult , Arginine/genetics , DNA Mutational Analysis , Disease Progression , Electrophysiology , Family , Female , Genes, Recessive , Glutamine/genetics , Humans , Male , Pedigree , Phenotype , Serine/geneticsABSTRACT
The far ultraviolet circular dichroism spectra of sheep beta-lipotropic hormone (beta-LPH) were recorded under different conditions of pH, temperature, salt concentration, and solvent composition. Results confirm the stability of the hormone in strong basic or acidic solutions; moreover, temperatures up to 50 degrees C do not seem to affect noticeably the conformation of beta-LPH. However, increasing the NaC1 concentration or addition of dioxane in the solution brings about a conformational transition of the chain, interpreted as an increase in the helical content. The method of Yang (Chen, Y.H., Yang, J. T. & Martinez, H. M. (1972) Biochemistry 11, 4120-4131) was used to compute the proportion of helical, beta, and unordered forms of the hormone chain. The proportions are compared with those obtained from Fasman's predictive method (Chou, P. Y & Fasman, G. D. (1974) Biochemistry 13, 211-221 and Chou, P. Y. & Fasman, G. D. (1974) Biochemistry 13, 222-245) based on the known amino acid sequence of beta-LPH.
Subject(s)
beta-Lipotropin , Amino Acid Sequence , Animals , Circular Dichroism , Dioxanes , Hydrogen-Ion Concentration , Osmolar Concentration , Protein Binding , Protein Conformation , Sheep , Spectrophotometry, Ultraviolet , TemperatureSubject(s)
Pituitary Gland/analysis , beta-Lipotropin , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Adrenal Glands/drug effects , Adrenal Glands/metabolism , Adrenocorticotropic Hormone/pharmacology , Amino Acid Sequence , Amino Acids/analysis , Animals , Biological Assay , Carboxypeptidases , Corticosterone/metabolism , Humans , Lipid Mobilization/drug effects , Peptide Fragments/analysis , beta-Lipotropin/pharmacologyABSTRACT
A new peptide having both lipolytic and melanotropic properties has been isolated from human pituitary glands. It has a molecular weight around 11,000, an amino acid composition different from the known lipolytic-melanotropic hormones, and an isoelectric point of 8.5. Although it is not entirely pure, there is no doubt that it differs from other known lipolytic-melanotropic substances in its total lack of methionine and tryptophan and its unusually high content of lysine and histidine. It has a melanocyte-stimulating hormone activity of 19 units/mug. As a lipolytic agent it is active with rabbit adipocytes, only slightly active with human cells and inactive with adipocytes from the rat.
Subject(s)
Lipid Metabolism , Peptides/isolation & purification , Pituitary Gland, Anterior/analysis , Pituitary Gland/analysis , Pituitary Hormones, Anterior/isolation & purification , Skin Pigmentation , Alanine , Biological Assay , Chromatography , Chromatography, Gel , Electrophoresis, Polyacrylamide Gel , Humans , Isoelectric Focusing , Peptides/analysis , Pituitary Hormones, Anterior/analysis , Radioimmunoassay , Tryptophan/analysisABSTRACT
Sheep gamma-lipotropic hormone (gamma-LPH) is a pituitary polypeptide made of 58 amino acids and is formed of the first 58 residues of beta-lipotropic hormone (beta-LPH). The C-terminal portion (41-58) of gamma-LPH is identical with the structure of beta-melanophore-stimulating hormone (beta-MSH). We hypothetized in 1967 that beta-LPH could be the biological precursor of beta-MSH and that gamma-LPH could be an intermediate compound. We demonstrated in 1974 that beta-LPH is actively synthesized in the bovine pituitaries. We now studied the biosynthesis of gamma-LPH by monitoring the incorporation of radioactive amino acids in beef pituitary slices. We separated gamma-LPH from the other radioactive proteins with a method previously described. We characterized the radioactive proteins by ion-exchange chromatography, gel filtration and polyacrylamide gel electrophoresis. Our results show that radioactive gamma-LPH was actively synthesized. This gamma-LPH has all the chemical characteristics of nonradioactive gamma-LPH. However, in the conditions used, we were unable to demonstrate biosynthesis of beta-MSH. These results suggest that gamma-LPH is biosynthesized more slowly than beta-LPH and that the conversion into beta-MSH, if it exists, is a slow or subactive process in the species studied.
