Glutamate Carboxypeptidase II - Discovery

Discovery

GCPII is expressed in many tissues, including the prostate, kidney, the small intestine, and the central and peripheral nervous system.

Indeed the initial cloning of the cDNA encoding the gene expressing PSMA was accomplished with RNA from a prostate tumor cell line, LNCaP. PSMA shares homology with the transferrin receptor and undergoes endcytosis but the ligand for inducing internalization has not been identified. It was found that PSMA was the same as the membrane protein in the small intestine responsible for removal of gamma-linked glutamates from polygammaglutamate folate. This enables the freeing of folic acid, which then can be transported into the body for use as a vitamin. This resulted in the cloned genomic designation of PSMA as FOLH1 for folate hydrolase.

PSMA(FOLH1)+ folate polygammaglutamate(n 1-7)---> PSMA (FOLH1) + folate(poly)gammaglutamate(n-1) + glutamate continuing until releasing folate.

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