Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model.
The mammalian multifunctional protein-2 (MFP-2, also called multifunctional enzyme 2, D-bifunctional enzyme or 17-beta-estradiol dehydrogenase type IV) was identified by several groups about a decade ago. It plays a central role in peroxisomal beta-oxidation as it handles most, if not all, peroxisomal beta-oxidation substrates. Deficiency of this enzyme in man causes a severe developmental syndrome with abnormalities in several organs but in particular in the brain, leading to death within the first year of life. Accumulation of branched-long-chain fatty acids and very-long-chain fatty acids and a disturbed synthesis of bile acids were documented in these patients. A mouse model with MFP-2 deficiency only partly phenocopies the human disease. Although the expected metabolic abnormalities are present, no neurodevelopmental aberrations are observed. However, the survival of these mice into adulthood allowed to document the importance of this enzyme for the normal functioning of the brain, eyes and testis. In the present review, the identification and biochemical characteristics of MFP-2, and the consequences of MFP-2 dysfunction in humans and in mice will be discussed.
Huyghe
Steven
S
Laboratory of Cell Metabolism, Department of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs en Navorsing II, bus 823, Herestraat 49, B-3000 Leuven, Belgium.
Mannaerts
Guy P
GP
Baes
Myriam
M
Van Veldhoven
Paul P
PP
D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000172:deficiency / Q000502:physiology*; D000015:Abnormalities, Multiple / Q000201:enzymology / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000254:growth & development; D004746:Enoyl-CoA Hydratase / Q000737:chemistry / Q000172:deficiency / Q000502:physiology*; D005124:Eye Abnormalities / Q000201:enzymology / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000172:deficiency / Q000502:physiology*; D009928:Organ Specificity; D064029:Peroxisomal Multifunctional Protein-2; D020675:Peroxisomes / Q000201:enzymology*; D013737:Testis / Q000002:abnormalities / Q000254:growth & development
D005227:Fatty Acids; D009097:Multienzyme Complexes; D015067:17-Hydroxysteroid Dehydrogenases; C491288:Hsd17b4 protein, mouse; D064029:Peroxisomal Multifunctional Protein-2; D004746:Enoyl-CoA Hydratase