hymecromone and Ichthyosis

Arylsulphatase C (ASC) activity in leukocytes and fibroblasts measured with 4-methylumbelliferylsulphate, is caused by at least two genetically different sulphatases. One of these is steroid sulphatase (STS). Depending on the substrate concentration, about 10-50% of the ASC activity in leukocytes can be attributed to sulphatases other than STS. Steroid sulphatase can be measured specifically with 4-methylumbelliferylsulphate as the fraction of total ASC activity which is inhibitable by dehydroepiandrosterone sulphate. Using this assay, the adjusted ASC activity in leukocytes from patients with X-linked ichthyosis was 2% of normal. Obligate heterozygotes showed reduced activity.

Topics: Arylsulfatases; Dehydroepiandrosterone; Female; Fluorometry; Genetic Linkage; Humans; Hymecromone; Ichthyosis; Kinetics; Leukocytes; Male; Steryl-Sulfatase; Sulfatases; X Chromosome

Recessive X-linked ichthyosis (RXLI) has its biochemical basis in a defect of the enzyme steroid sulfatase. Since several studies have reported a simultaneous deficiency of arylsulfatase C and steroid sulfatase it has been hypothesized that both enzymes are identical. In human hair follicles, however, hydrolytic activity for 4-methylumbelliferone sulfate, the substrate for arylsulfatase C, is found, while dehydroepiandrosterone sulfate is not hydrolyzed at all. These findings suggested the possible existence of two different enzymes. In the present paper structure-activity studies and molecular energy calculations are used for the demonstration that the remaining sulfatase activity in hair follicles of RXLI patients can be explained on the basis of the assumption that the enzyme has not lost its total function but has become less efficient.

Topics: Adolescent; Adult; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Equilenin; Estrone; Female; Genetic Linkage; Hair; Humans; Hymecromone; Ichthyosis; Male; Middle Aged; Substrate Specificity; Sulfatases; X Chromosome