Biochemical and Morphologic Aspects of Peroxisomes in the Human Rectal Mucosa: Diagnosis of Zellweger Syndrome Simplified by Rectal Biopsy

Abstract

ABSTRACT. Rectal mucosa biopsy specimens from five controls and three infants with Zellweger syndrome were investigated morphologically and biochemically to elucidate peroxisomal structure and functions in the human rectal mucosa and to develop a simple method for an early postnatal diagnosis of peroxisomal deficiency disorders. After the alkaline 3,3'-diaminobenzidine reaction, peroxisomes of the rectal mucosa from the controls could be identified, electron microscopically, but not light microscopically. However, they were strongly stained using an immunoenzyme technique applied to semi-thin Epon sections and then were clearly visible under the light microscope. However, no positive granules were observed in the specimens of infants with Zellweger syndrome, using either of the two staining techniques. On immunoblot analysis, immunoreactive proteins of peroxisomal acyl-CoA oxidase and 3-ketoacyl-CoA thiolase were present in rectal mucosae from the controls; however, these enzyme proteins were not detected in tissues from the patients. Activity of dihydroxyacetone phosphate acyltransferase was detectable in rectal mucosae from the controls, whereas in those from infants with Zellweger syndrome, the activity of this enzyme was greatly reduced. These observations indicate that the peroxisomal structure and multiple functions are present in the rectal mucosa and that rectal biopsy is of potential value for the early and less invasive detection of Zellweger syndrome and other peroxisomal disorders. (Pediatr Res 24: 723-727, 1988) Abbreviations ZS, Zellweger syndrome DHAP-AT, dihydroxyacetone phosphate acyltransferase DAB, 3,3'-diaminobenzidine BSA, bovine serum albumin HRP, horseradish peroxidase LM, light microscope SDS, sodium dodecyl sulfate PAGE, polyacrylamide gel electrophoresis

Peroxisomes and Peroxisomal Enzymes in the Human Fetal Small Intestine

“…Activities of peroxisomal P-oxidation en zymes have been detected in normal human colonic [7] and rectal [8] mucosa. In these intestinal segments, peroxisomes are impor tant for fatty acid metabolism.…”

“…The precise role that peroxisomes play in intestinal epithelial cells is not well defined. However, it has recently been demonstrated that they are involved in the p-oxidation of fatty acids [7][8][9][10] and in the biosynthesis of plasmalogens [8],…”

Temperature-Sensitive Mutation of PEX6 in Peroxisome Biogenesis Disorders in Complementation Group C (CG-C): Comparative Study of PEX6 and PEX1

“…Lignoceric acid (C24:0) oxidation (27) and DHAP-AT activities were measured using 14 C-labeled substrates as described previously (28).…”

Newly Identified Chinese Hamster Ovary Cell Mutants Are Defective in Biogenesis of Peroxisomal Membrane Vesicles (Peroxisomal Ghosts), Representing a Novel Complementation Group in Mammals

“…Peroxisomal DHAP-ATase was measured as described (60). Survival rate of P9OH/UV-and P12/UV-resistant cells was expressed as a percentage of the unselected control (12 peroxisomes in the wild-type cells but mostly stays in the cytosol, apparently rather degraded more rapidly in the ZP119.…”