The GLUD1 Knockout Raji Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphocyte cell line, engineered to disrupt the GLUD1 gene. This loss-of-function model is generated through CRISPR/Cas9-mediated gene disruption, resulting in a heterogeneous pool of GLUD1-null cells that enables the study of glutamate dehydrogenase 1 function without clonal selection biases. The polyclonal format preserves genetic diversity inherent to the Raji background, facilitating robust investigation of glutamine metabolism and its role in B-cell lymphoma biology. Researchers can utilize this tool for a wide range of metabolic and oncological assays, including Western blotting, RT-qPCR, and glutamate dehydrogenase activity measurements, to confirm target disruption and downstream effects. The product is provided as a ready-to-expand population, ensuring immediate experimental deployment.
Raji cells are an Epstein-Barr virus (EBV)-positive human Burkitt’s lymphoma B lymphocyte line originally established from a Nigerian patient. These lymphoblastoid cells express canonical B-cell surface markers CD19 and CD20, and they serve as a well-characterized model for B-cell malignancies, immune signaling, and lymphomagenesis. The Raji cell line is extensively employed in cancer research to investigate mechanisms of B-cell transformation, apoptotic signaling, and response to chemotherapeutic agents. Its EBV-positive status further allows studies on viral oncogenesis and host-virus interactions. Within this context, the GLUD1 knockout provides a focused platform to dissect the contribution of glutamate dehydrogenase to the unique metabolic demands of aggressive B-cell lymphomas.
GLUD1 encodes glutamate dehydrogenase 1, a mitochondrial matrix enzyme that catalyzes the reversible oxidative deamination of glutamate to ??-ketoglutarate and ammonia, using NAD? or NADP? as cofactors. This reaction links amino acid metabolism to the tricarboxylic acid (TCA) cycle and ammonia homeostasis. GLUD1 activity is allosterically regulated by ADP and leucine as activators, and by GTP and SIRT4-mediated ADP-ribosylation as inhibitors; it is also influenced by AMPK signaling. Downstream, GLUD1 generates ??-ketoglutarate for TCA cycle anaplerosis, ammonia for biosynthetic pathways, and NADH/NADPH for redox balance. The enzyme operates within a pathway where glutamine is first deaminated by glutaminase (GLS) to glutamate, which GLUD1 then converts to ??-ketoglutarate, with glutamine synthetase (GLUL) providing the reverse flux. Interacting partners include SIRT4, GLUL, and GLS, forming a node in nitrogen and energy metabolism. GLUD1 thus sits at the intersection of glutaminolysis, TCA cycle replenishment, and redox control, making it critical for rapidly proliferating cells.
In the Raji B-lymphoma background, GLUD1 disruption is expected to severely impair glutamine-dependent metabolic pathways. Burkitt??s lymphoma cells often display glutamine addiction, relying on glutaminolysis for energy production, biosynthesis, and maintenance of redox homeostasis. Knockout of GLUD1 in these cells likely blocks the conversion of glutamate to ??-ketoglutarate, leading to reduced TCA cycle flux, accumulation of glutamate, and diminished production of ammonia and NAD(P)H. This metabolic perturbation can impact cell proliferation, survival under stress, and sensitivity to apoptotic stimuli. The polyclonal GLUD1 knockout Raji model thus offers a physiologically relevant system to examine how B-cell lymphomas adapt to metabolic stress and to identify vulnerabilities that can be therapeutically exploited.
This GLUD1 knockout product is suited for diverse research applications in cancer metabolism, particularly for studying glutamine addiction, metabolic reprogramming, and drug resistance in B-cell malignancies. It enables detailed metabolic flux analyses using techniques like Seahorse extracellular flux assays, liquid chromatography-mass spectrometry-based metabolomics, and glutamine/glutamate quantification. Typical functional readouts include MTT or CellTiter-Glo proliferation assays, Annexin V apoptosis assays, and flow cytometric analysis of cell cycle and apoptotic markers. The model supports B-cell lymphoma disease modeling and drug sensitivity screens targeting metabolic enzymes or signaling nodes such as AMPK and SIRT4. Investigators can also explore the interplay between GLUD1 and glutamate-glutamine cycle components GLS and GLUL, providing insights into compensatory mechanisms upon GLUD1 loss. For further technical details and ordering information, please contact Ascent Research.
