heparitin-sulfate and Metabolism--Inborn-Errors

A number of genetic disorders are caused by mutations in the genes encoding glycosyltransferases and sulfotransferases, enzymes responsible for the synthesis of sulfated glycosaminoglycan (GAG) side chains of proteoglycans, including chondroitin sulfate, dermatan sulfate, and heparan sulfate. The phenotypes of these genetic disorders reflect disturbances in crucial biological functions of GAGs in human. Recent studies have revealed that mutations in genes encoding chondroitin sulfate and dermatan sulfate biosynthetic enzymes cause various disorders of connective tissues. This minireview focuses on growing glycobiological studies of recently described genetic diseases caused by disturbances in biosynthetic enzymes for sulfated GAGs.

Topics: Chondroitin Sulfates; Connective Tissue Diseases; Dermatan Sulfate; Glycosaminoglycans; Heparitin Sulfate; Humans; Metabolism, Inborn Errors

Topics: Animals; Carbohydrate Sequence; Evolution, Molecular; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Metabolism, Inborn Errors; Models, Chemical; Models, Molecular; Molecular Sequence Data

Topics: alpha-Galactosidase; Arylsulfatases; beta-Galactosidase; Cystine; Fabry Disease; G(M1) Ganglioside; G(M2) Ganglioside; Galactosylceramidase; Gangliosidoses; Genetic Carrier Screening; Glycoproteins; Heparitin Sulfate; Humans; Hydrolases; Isoelectric Focusing; Isoenzymes; Kinetics; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Lipid Metabolism, Inborn Errors; Lysosomes; Metabolism, Inborn Errors; Molecular Weight; Mucolipidoses; Niemann-Pick Diseases; Sphingolipidoses; Sphingomyelin Phosphodiesterase

Lysosomal hydrolases participate substantially in the degradation of all classes of biological macromolecules. They act physiologically within the lysosome. The enzymes are either primarily included within primary lysosomes or are transported to these cell organelles after secretion and subsequent adsorptive pinocytosis. The involvement of these enzymes in a variety of pathological conditions can be understood on the basis of the known functions of lysosomal hydrolases. Inactivity of one or several of the enzymes causes lysosomal storage disorders. Similar metabolic consequences are found when the enzymes are unable to be concentrated within the lysosome. Lysosomal hydrolases participate, furthermore, in the pathogenesis of numerous diseases. A distinction can be made between lysosomal overload, pathologically-increased enzyme secretion into the extracellular space, and a release of lysosomal enzymes into the cytosol.

Topics: Acid Phosphatase; Cytosol; Extracellular Space; Genes; Glycoproteins; Heparitin Sulfate; Humans; Hydrolases; Lysosomes; Metabolism, Inborn Errors; Mucopolysaccharidoses; Mutation; Pinocytosis; Sphingolipidoses