The biogenesis, assembly and import of the peroxisomal enzyme catalase
was studied in human skin fibroblasts from control persons and from p
atients with the Zellweger syndrome. For this purpose, two monoclonal
antibodies were generated which are able to discriminate between the m
onomeric or dimeric form and the tetrameric, enzymically active confor
mation of the enzyme. Metabolic labelling studies showed that catalase
is assembled to the tetrameric conformation within one hour after its
synthesis, while it is still in the cytosol of the cell. Subsequently
, the enzyme becomes particle-bound in the control cells, a process th
at is retarded by addition of the catalase inhibitor 3-amino-1,2,4-tri
azole. However, the tetramer remains in the cytosol in cells from Zell
weger patients. It is concluded that newly synthesized catalase can be
assembled to a tetramer in the cytosol in human skin fibroblasts. Unf
olding of this tetramer prior to import into peroxisomes is indicated.