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Characterization of the enzymatic activity of PSM: Comparison with brain NAALADase
Author(s) -
Tiffany Carol W.,
Lapidus Rena G.,
Merion Aviva,
Calvin David C.,
Slusher Barbara S.
Publication year - 1999
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19990401)39:1<28::aid-pros5>3.0.co;2-a
Subject(s) - glutamate carboxypeptidase ii , lncap , enzyme , dipeptidase , biochemistry , prostate , peptide , prostate cancer , chemistry , enzyme kinetics , enzyme assay , biology , active site , cancer , genetics
BACKGROUND The prostate cancer marker prostate‐specific membrane antigen (PSM) is highly homologous to the brain enzyme N‐acetylated alpha‐linked acidic dipeptidase (NAALADase). NAALADase is known to cleave terminal carboxy glutamates from both the neuronal peptide N‐acetylaspartylglutamate (NAAG) and folate polyglutamate. In this report, we compare the NAAG hydrolyzing activity of NAALADase and the prostate enzyme PSM. METHODS Using a NAAG hydrolytic radioenzymatic assay, we compared the pharmacological and kinetic properties of the brain and prostate enzymes. RESULTS Eight normal prostate tissues from different species exhibited NAAG hydrolyzing activity. Among 14 cancer cell lines examined, activity was observed in human LNCaP, PC‐82, and rat Dunning G and AT‐1 cells. Brain exhibited membrane‐localized activity exclusively, while the prostate enzyme had activity in both membrane and cytosolic fractions. The only observed pharmacological difference was the sensitivity to their putative substrates, folate polyglutamate and NAAG. Kinetically, the soluble form of the prostate enzyme had two catalytic sites, while the membrane‐bound form exhibited single site kinetics with a lower V max than the brain enzyme, which may suggest a less active hydrolase in the prostate. CONCLUSIONS The brain enzyme NAALADase and the prostate enzyme PSM are remarkably similar. The importance of the differences in substrate specificities and kinetic parameters remains to be elucidated. Prostate 39:28–35, 1999. © 1999 Wiley‐Liss, Inc.