α-Ketoglutarate Family Related Drug Discovery Products
Creative Biolabs has the assays you can rely on for high throughput screening, lead optimization, characterizing and discovering targets, and uncovering the complexity of disease pathways. We can offer membrane protein in vitro assay kits that save valuable laboratory time and is ideal for high throughput screening.
Membrane protein stable cell lines are widely used in many areas of biomedical research. Creative Biolabs can offer membrane protein stable cell lines to stablish in vitro models for High Throughput Screening.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
The mitochondrial matrix's tricarboxylic acids (TCA) cycle continues a series of metabolic oxidative processes using carbon obtained from carbs to make the reducing equivalents NADH and FADH2, which are required by the mitochondrial electron transport chain to produce the energetic molecule ATP. The metabolite α-ketoglutarate (αKG), which is involved in a variety of physiological processes besides cellular metabolism, is known to have pleiotropic activity. Two weakly acidic carboxylic groups and a ketone group in the α-position, which affects the compound's reactivity, are present in the αKG molecule. This ketoacid is the end product of the reversible isocitrate decarboxylation reaction catalyzed by the mitochondrial and cytoplasmic isoforms of NADP-dependent isocitrate dehydrogenase (IDH1/2), respectively.
Fig.1. αKG biosynthetic pathways. (Abla, 2020)
Creative Biolabs is proud to offer a series of α-ketoglutarate family drug discovery tools with the best quality:
Overview of α-Ketoglutarate Family
The natural ligand for GPR99 is α-ketoglutartate (oxaloglutarate), which led to the receptor's renaming to Oxaloglutrate Receptor-1 (OXGR1). α-Ketoglutarate stimulates the Gq-coupled OXGR1 receptor. It is only found on the apical membrane of PPICs in the CNT and CCD, where it is primarily expressed in adult kidneys. The synthesis and secretion processes in the proximal tubule tightly control the levels of the OXGR1 ligand, α-ketoglutarate, in the urine. As a result, urinary α-ketoglutarate is several orders of magnitude higher than the plasma concentration. The glomeruli easily filter α-ketoglutarate, which the proximal tubule normally reabsorbs. The best way to understand α-ketoglutarate is as a Kreb's cycle intermediate. However, the proximal tubule also produces α-ketoglutarate de novo as a byproduct of the ammoniagenesis pathway, which is brought about by the deamination of glutamine and glutamate. α-Ketoglutarate is either catabolized or released into the tubular lumen after synthesis in the proximal tubule.
Fig.2. Signal transduction pathway of OXGR1. (Lazo-Fernandez, 2018)
α-Ketoglutarate Family Drug Discovery
αKG is engaged in numerous physiological functions as well as various cell processes. Studies on metabolomics have revealed that αKG plays a crucial role in the metabolic reprogramming necessary for the survival and growth of cancer cells. Furthermore, as an allosteric activator of PHDs, αKG plays a crucial role in controlling the hypoxia response and epigenetic changes, two important factors in neoplastic transformation. This situation presents a chance to take advantage of αKG's complex influence on metabolic rewiring and hypoxic adaptations as a potential adjuvant therapeutic approach to slow the growth of tumors.
References
- Abla, H.; et al. The multifaceted contribution of α-ketoglutarate to tumor progression: An opportunity to exploit? Seminars in cell & developmental biology. 2020, 98: 26-33.
- Lazo-Fernandez, Y.; et al.α-Ketoglutarate stimulates pendrin-dependent Cl− absorption in the mouse CCD through protein kinase C. American Journal of Physiology-Renal Physiology. 2018, 315(1): F7-F15.
