The human peroxisomal multifunctional protein involved in bile acid synthesis: activity measurement, deficiency in Zellweger syndrome and chromosome mapping.
The dehydrogenation of 24R,25R-varanoyl-CoA, the physiological intermediate formed during the peroxisomal breakdown of the bile acid intermediate trihydroxycoprostanic acid, was studied in human liver. The reaction appeared to be catalyzed by two different enzymes. A first one, present in the cytosol, did not discriminate between the four possible varanoyl-CoA isomers and did not require the CoA moiety. The second enzymic activity was associated with peroxisomes and acted only on the 24R,25R-isomer, in which the 24-hydroxy group possesses the D-configuration. The D-specific dehydrogenase is part of a 79 kDa protein which represents the human counterpart of a recently discovered second multifunctional protein in rat liver peroxisomes, named multifunctional protein 2 (MFP-2). Human MFP-2, like its rat counterpart, is also responsible for the formation (by hydratation) of 24R,25R-varanoyl-CoA. A deficiency of MFP-2 in Zellweger liver could be demonstrated immunologically by using antibodies against the rat enzyme and enzymically -- after removal of the cytosol -- by using 24R,25R-varanoyl-CoA. The gene coding for MFP-2 was mapped to chromosome 5q2.3.
Novikov
D
D
Katholieke Universiteit Leuven, Campus Gasthuisberg, Departement Moleculaire Celbiologie, Afdeling Farmacologie, Belgium.
Dieuaide-Noubhani
M
M
Vermeesch
J R
JR
Fournier
B
B
Mannaerts
G P
GP
Van Veldhoven
P P
PP
D015094:3-Hydroxyacyl CoA Dehydrogenases; D000818:Animals; D001483:Base Sequence; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002852:Chromatography, Ion Exchange; D002874:Chromosome Mapping; D004746:Enoyl-CoA Hydratase; D006801:Humans; D007535:Isomerases; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D063994:Peroxisomal Bifunctional Enzyme; D051381:Rats; D013237:Stereoisomerism; D013347:Subcellular Fractions / Q000378:metabolism; D015211:Zellweger Syndrome / Q000235:genetics / Q000378:metabolism*
D001647:Bile Acids and Salts; D009097:Multienzyme Complexes; D015094:3-Hydroxyacyl CoA Dehydrogenases; C576253:EHHADH protein, human; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases