title: Activity modulation of the fast and slow isozymes of human cytosolic low-molecular-weight acid phosphatase (ACP1) by purines.
abstract: The activity modulation of homogeneous isozymes of the human cytosolic M(r) 18,000 acid phosphatase (ACP1) by purines has been investigated. A pronounced difference in the response of fast and slow isozymes of the same genetic type was observed, while identical properties were found for fast isozymes encoded by different alleles (ACP1 X A, B and C), as well as for the corresponding slow isozymes. The catalytic rate constant (kc) of the fast isozymes was increased 5.1-fold by hypoxanthine and decreased 40% by adenine, while the kc of the slow isozymes was unaffected by hypoxanthine but increased 4.6-fold by adenine. This finding and the genetically-determined differences in the relative quantities of the fast and slow isozymes account for the well-known phenotypic differences in activity modulation. The kinetic results strongly indicate that the effector binds to the free enzyme, as well as to the enzyme-substrate complex. Activating effectors showed a higher affinity for the free enzyme than for the enzyme-substrate complex, while the reverse was true with the inhibitor. The results exclude the possibility that effector and substrate bind to the same site of the enzyme; parasteric binding to adjacent sites is suggested.
authors.affiliation: Institute of Forensic Genetics, University of Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Dissing
authors.forename: B
authors.initials: B
authors.lastname: Rangaard
authors.forename: U
authors.initials: U
authors.lastname: Christensen
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism*; D000225:Adenine / Q000378:metabolism; D000483:Alleles; D002384:Catalysis; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008970:Molecular Weight; D011687:Purines / Q000378:metabolism*
chemical_list: D007042:Hypoxanthines; D007527:Isoenzymes; D011687:Purines; D019271:Hypoxanthine; D000135:Acid Phosphatase; D000225:Adenine