ABSTRACT
After validating a superoxide dismutase (SOD) assay, this enzyme was measured together with a large series of cell age sensitive marker enzymes, in the erythrocytes of 24 persons with the 24 persons without Down syndrome. In addition to the expected elevation of SOD-1, significant elevations of erythrocyte glutathione peroxidase (GSHPxase) and phosphofructokinase activities were found in Down syndrome. None of these changes could be accounted for by a decreased mean red cell age. The elevation of GSHPxase was also found in lymphoid cells but does not represent a gene dose effect at this locus. Rather, the elevation of GSHPxase in Down syndrome may represent an adaptive metabolic response to the increased hydrogen peroxide produced by the triplicated SOD-1 gene dose in trisomy 21. Since tissue GSHPxase activity can be manipulated via the enzyme's obligatory selenium co-factor, our data suggest the need to establish blood and tissue levels of selenium in Down syndrome and to correlate selenium, GSHPxase and phenotypic dysfunction in this disorder.
Subject(s)
Down Syndrome/enzymology , Erythrocytes/enzymology , Glutathione Peroxidase/blood , Lymphocytes/enzymology , Peroxidases/blood , Superoxide Dismutase/blood , Adult , Animals , Cattle , Cells, Cultured , Fetal Blood/metabolism , Glutathione Peroxidase/genetics , Humans , Infant, Newborn , Intellectual Disability/enzymology , Kinetics , Reference Values , Superoxide Dismutase/geneticsABSTRACT
Porcine parathyroid gland slices were incubated with 3H-labeled amino acids in order to label tissue proteins. After incubation a crude hormonal extract was prepared and analyzed by chromatography on carboxymethylcellulose. Among the three radioactive peaks which were detected in the eluate, two were identified as parathyroid hormone and proparathyroid hormone. Based on thin layer gel filtration in the presence of 6 M guanidine-HCl, the proparathyroid hormone had a molecular weight of 11,500 compared to about 9600 for parathyroid hormone. Radioisotope sequence analysis of the proparathyroid hormone revealed a partial sequence of: Lys1-Pro2-Ile3-Lys4-Lys5-Arg6-Ser7-Val8-Ser9--Ile11--Met14--Gly18--Ser22--Ser23---. Thus, from position 7 onward the relative position of each amino acid tested in this molecule corresponded exactly to that in the porcine parathyroid hormone sequence. The conservation of a similar, though not identical, basic hexapeptide grouping Lys-X-Y-Lys-Lys-Arg- at the amino terminal region of the prohormone in all species examined thus far (porcine, human, and bovine) suggests that this segment of the molecule may play an important role in the conversion of the prohormone to the hormone.
