title: Recent developments in the investigation of inherited metabolic disorders using cultured human cells.
abstract: Thepurpose of this paper is to share experience with our systems and review recent "in vitro" methods using intact cells (fibroblasts, amniocytes) in which entire metabolic pathways can be probed for inherited metabolic defects reflected by elevations of intermediates determined by tandem mass spectrometry, HPLC, or gas chromatography-mass spectrometry. Currently, one can explore the integrity of mitochondrial fat oxidation, peroxisomal degradation of methyl-branched fatty acids (e.g., pristanate), and the mitochondrial degradation of the branched chain amino acids (leucine, valine, and isoleucine). For many of the diseases, the specific defect can be recognized from the acylcarnitine profile resulting from incubation of the intact cells with stable-isotope-labeled precursors to the particular pathway. This approach has also been successful in identifying new inherited metabolic disorders, biochemical correlation with clinical phenotypes of individual defects, and sequential oxidation of fatty acids by peroxisomal-mitochondrial interaction.
authors.affiliation: Kimberly H. Courtwright & Joseph W. Summers Institute of Metabolic Disease, Baylor University Medical Center, Dallas, Texas, 75226, USA. cr.roe@baylordallas.edu
authors.forename: C R
authors.initials: CR
authors.lastname: Roe
authors.forename: D S
authors.initials: DS
authors.lastname: Roe
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency / Q000235:genetics; D002331:Carnitine / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency / Q000235:genetics; D002460:Cell Line; D044943:Fatty Acid Desaturases / Q000172:deficiency / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000172:deficiency / Q000235:genetics; D019308:Palmitic Acid / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D019308:Palmitic Acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; D044943:Fatty Acid Desaturases; D063991:Mitochondrial Trifunctional Protein; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine