title: Molecular analysis of peroxisomal beta-oxidation enzymes in infants with peroxisomal disorders indicates heterogeneity of the primary defect.
abstract: Immunoblot analysis of peroxisomal beta-oxidation enzymes proteins was carried on liver samples from 15 patients with peroxisomal disorders in which accumulation of very long chain fatty acids was always observed in plasma. In 11 cases including 4 cerebro-hepatorenal syndrome (CHRS), 4 neonatal adrenoleukodystrophy (NALD) and 3 infantile Refsum's disease, the liver peroxisomes could not be detected by electron microscopy. Immunoblot analysis revealed the absence, or presence in weak amounts, of the 72-kDa subunit of acyl-CoA oxidase, and the complete absence of the 52-kDa and 21-kDa subunits which are processed from the 72-kDa. The bifunctional protein (78-kDa) was absent or very reduced, as was the mature form of peroxisomal 3-ketoacyl-CoA thiolase (41-kDa). Multiple defects of peroxisomal beta-oxidation enzymes may be caused by an absence of synthesis or an inability to import proteins into peroxisomes in these patients. One patient, diagnosed as NALD, had no detectable liver peroxisomes but the presence, in normal amounts, of the three peroxisomal beta-oxidation enzyme proteins suggests that the transport of these enzymes into "peroxisomal ghosts" was still intact. The last 3 patients, clinically diagnosed as NALD, had normal liver peroxisomes. One patient had an isolated deficiency of the bifunctional protein and the 2 others had normal amounts of the 3 peroxisomal beta-oxidation enzymes, as shown by immunoblotting. This suggests that import and translocation of some peroxisomal proteins had occurred and that a mechanism is therefore required to explain the defect in these patients.
authors: INSERM U 56, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
authors: S
authors: S
authors: Guerroui
authors: P
authors: P
authors: Aubourg
authors: W W
authors: WW
authors: Chen
authors: T
authors: T
authors: Hashimoto
authors: J
authors: J
authors: Scotto
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics* / Q000302:isolation & purification; D000326:Adrenoleukodystrophy / Q000201:enzymology / Q000235:genetics; D002374:Catalase; D004746:Enoyl-CoA Hydratase / Q000235:genetics* / Q000302:isolation & purification; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics*; D015151:Immunoblotting; D007223:Infant; D007535:Isomerases; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure; D008830:Microbodies / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000235:genetics* / Q000302:isolation & purification; D010084:Oxidation-Reduction; D063994:Peroxisomal Bifunctional Enzyme; D012035:Refsum Disease / Q000201:enzymology / Q000235:genetics; D015211:Zellweger Syndrome / Q000201:enzymology / Q000235:genetics
chemical_list: D005227:Fatty Acids; D009097:Multienzyme Complexes; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002374:Catalase; D006836:Hydro-Lyases; C576253:EHHADH protein, human; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases