A novel HPLC-based method to diagnose peroxisomal D-bifunctional protein enoyl-CoA hydratase deficiency.

D-bifunctional protein (D-BP) plays an indispensable role in peroxisomal beta-oxidation, and its inherited deficiency in humans is associated with severe clinical abnormalities. Three different subtypes of D-BP deficiency can be distinguished: 1) a complete deficiency of D-BP (type I), 2) an isolated D-BP enoyl-CoA hydratase deficiency (type II), and 3) an isolated D-BP 3-hydroxyacyl-CoA dehydrogenase deficiency (type III). In this study, we developed a method to measure D-BP dehydrogenase activity independent of D-BP hydratase (D-BP HY) activity to distinguish between D-BP deficiency type I and type II, which until now was only possible by mutation analysis.

Reinvestigation of peroxisomal 3-ketoacyl-CoA thiolase deficiency: identification of the true defect at the level of d-bifunctional protein.

In this report, we reinvestigate the only patient ever reported with a deficiency of peroxisomal 3-ketoacyl-CoA thiolase (THIO). At the time when they were described, the abnormalities in this patient, which included accumulation of very-long-chain fatty acids and the bile-acid intermediate trihydroxycholestanoic acid, were believed to be the logical consequence of a deficiency of the peroxisomal beta-oxidation enzyme THIO. In light of the current knowledge of the peroxisomal beta-oxidation system, however, the reported biochemical aberrations can no longer be explained by a deficiency of this thiolase.

Peroxisomal fatty acid alpha- and beta-oxidation in humans: enzymology, peroxisomal metabolite transporters and peroxisomal diseases.

Peroxisomes are subcellular organelles with an indispensable role in cellular metabolism. The importance of peroxisomes for humans is stressed by the existence of a group of genetic diseases in humans in which there is an impairment in one or more peroxisomal functions. Most of these functions have to do with lipid metabolism including the alpha- and beta-oxidation of fatty acids.

Molecular basis of D-bifunctional protein deficiency.

Peroxisomal disorders appear with a frequency of 1:5000 in newborns. They are caused either by peroxisomal assembly defects or by deficiencies of single peroxisomal enzymes. The phenotypes vary widely: affected humans may die very early in life within a few days to several months as a result of the impairment in essential peroxisomal functions as, for example, in Zellweger syndrome, or they may show only minor disabilities as is in acatalasemia.

Lipid metabolism in peroxisomes: enzymology, functions and dysfunctions of the fatty acid alpha- and beta-oxidation systems in humans.

Peroxisomes are subcellular organelles present in virtually all eukaryotic cells catalysing a number of indispensable functions in cellular metabolism. The importance of peroxisomes in man is stressed by the existence of an expanding group of genetic diseases in which there is an impairment in one or more peroxisomal functions. One of the major functions of peroxisomes concerns their role in lipid metabolism, which includes: (i) fatty acid betaoxidation; (ii) ether phospholipid synthesis; (iii) fatty acid alpha-oxidation; and (iv) isoprenoid biosynthesis.