GCH1 Antibody

Antigen Characteristics

GCH1 (GTP cyclohydrolase 1) catalyzes the conversion of GTP to dihydroneopterin triphosphate, initiating BH4 synthesis. Key features include:

• Isoforms: Functional GCH1 and enzymatically inactive splice variants.

• Subcellular Localization: Primarily cytoplasmic, with mitochondrial associations observed in some studies .

• Clinical Relevance: Mutations linked to dopa-responsive dystonia and malignant hyperphenylalaninemia .

Antibody Types and Applications

GCH1 antibodies are validated for diverse techniques. Below is a comparative analysis of commercially available antibodies:

Key Notes:

• Polyclonal vs. Monoclonal: Polyclonal antibodies (e.g., Proteintech, Boster Bio) offer broader epitope recognition, while monoclonal antibodies (e.g., Thermo Fisher) provide higher specificity .

• Cross-Reactivity: Most antibodies target conserved regions, enabling detection across species (human, mouse, rat) .

Research Findings

GCH1 antibodies have elucidated mechanisms in cancer, neurology, and immunology:

Cancer Biology

Glioblastoma: GCH1 overexpression reduces ROS, enabling tumor survival. Knockdown decreases self-renewal and CD44 expression .
TNBC: GCH1-driven IDO1 activation depletes tryptophan, suppressing antitumor immunity. Inhibition with DAHP (GCH1 inhibitor) enhances PD-1 blockade efficacy .

Neurological Disorders

• Dopa-Responsive Dystonia: Mutations reduce GCH1 activity by 80%, causing dopamine/serotonin deficiency. L-Dopa therapy alleviates symptoms .

• Pain Sensitivity: GCH1 modulates neuropathic pain pathways, though mechanisms remain under investigation .

Technical Considerations

• Antigen Retrieval: IHC protocols typically require citrate buffer (pH 6.0) or TE buffer (pH 9.0) .

• Storage: Most antibodies are stable at -20°C in PBS with 50% glycerol and 0.02% sodium azide .

• Validation: Protocols for WB and IHC are available for select antibodies (e.g., Proteintech 28501-1-AP, Thermo Fisher MA5-27278) .

Clinical and Therapeutic Implications

• Therapeutic Targeting: Inhibiting GCH1 in TNBC may synergize with immunotherapy by reducing IDO1-driven immunosuppression .

• Biomarker Potential: Elevated GCH1 correlates with poor prognosis in glioma and TNBC, suggesting utility in stratifying high-risk patients .