Glutamate carboxypeptidase II

Glutamate carboxypeptidase II (GCPII), also known as prostate-specific membrane antigen (PSMA), is an enzyme that in humans is encoded by the FOLH1 gene. This enzyme is a type II transmembrane glycoprotein and is involved in the hydrolysis of the neuropeptide N-acetylaspartylglutamate (NAAG) to N-acetylaspartate (NAA) and glutamate.

Function

Glutamate carboxypeptidase II plays a crucial role in the central nervous system by regulating the levels of the neurotransmitter glutamate. Glutamate is an important excitatory neurotransmitter, and its dysregulation is associated with various neurological disorders, including Alzheimer's disease, schizophrenia, and epilepsy. GCPII is also expressed in the prostate gland, where it is referred to as prostate-specific membrane antigen (PSMA). PSMA is a marker for prostate cancer and is used in diagnostic imaging and targeted therapy.

Structure

GCPII is a zinc-dependent metallopeptidase and belongs to the M28 family of peptidases. The enzyme consists of a large extracellular domain, a single transmembrane domain, and a short intracellular tail. The extracellular domain contains the active site, which binds to zinc ions essential for its enzymatic activity.

Clinical Significance

GCPII is a target for the diagnosis and treatment of prostate cancer. PSMA expression is significantly upregulated in prostate cancer cells compared to normal prostate tissue, making it a valuable biomarker. Radiolabeled PSMA inhibitors are used in positron emission tomography (PET) imaging to detect prostate cancer metastases. Additionally, PSMA-targeted therapies, such as PSMA-targeted radioligand therapy, are being developed to treat advanced prostate cancer.

Research

Research on GCPII is ongoing to better understand its role in neurological disorders and to develop new therapeutic strategies. Inhibitors of GCPII are being investigated for their potential to modulate glutamate levels in the brain and treat conditions like neuropathic pain and cognitive disorders.

See Also

• Prostate-specific antigen
• Neurotransmitter
• Metallopeptidase
• Prostate cancer