The human peroxisomal multifunctional protein involved in bile acid synthesis: activity measurement, deficiency in Zellweger syndrome and chromosome mapping

AbstractThe 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. ©1997 Elsevier Science B.V. All rights reserved