Sulfate metabolism in brain

Abstract

The mammalian brain actively metabolizes inorganic sulfate to 3'-phosphoadenosine 5'-phosphosulfate and a number of sulfated compounds. There are enzymes which desulfate or dephosphorylate 3'-phosphoadenosine 5'-phosphosulfate in the brain. The sulfotransferases of brain catalyze the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to form sulfated compounds, such as the sulfated compounds, such as the sulfomucopolysaccharides, sulfatides, serotonin sulfate and other sulfated glycosphingolipids. Mucopolysaccharides which include hyaluronic acid, chondroitin sulfates, dermatan sulfate and heparan sulfate have been isolated from the brain of various species as well as from peripheral nerves and spinal cord. Heparan sulfate, dermatan sulfate or other types of mucopolysaccharides accumulate in the genetic diseases under the class of mucopolysaccharidoses. The defect appears to be faulty degradation of the mucopolysaccharides. A deficiency of the enzyme β-galactosidase in pseudo-Hurler disease (generalized gangliosidosis) has been demonstrated. The polyionic nature of the mucopolysaccharides, their presence in high concentrations in the synaptic vesicles, the variation in their concentration with age in the rat and human brain and their abnormal accumulation in genetic diseases associated with mental retardation would all suggest an important role for mucopolysaccharides in brain function. Sulfatide is primarily a myelin lipid, although its presence has been detected also in non-myelin structures of the brain. Excessive accumulation of sulfatides occurs in metachromatic leukodystrophy, a genetic disease characterized by extensive damage to myelin. The biochemical defect in this disease is a deficiency of the enzyme arylsulfatase A which is involved in the degradation of sulfatides. Globoid leukodystrophy is characterized by demyelination and a marked decrease in the concentration of sulfatides. A deficiency of cerebroside sulfotransferase in this disease has been indicated. Studies in the developing rat brain and in human brain of various age groups reveal a relationship between brain maturation and the synthesis of sulfatides and mucopolysaccharides. Malnutrition, when it coincides with the period of active myelination, affects the synthesis of various lipids including sulfatides in brain.