concept

α-ketoglutarate

Also known as: α-KG, αKG, alpha-ketoglutarate

Facts (18)

Sources

Dietary interventions as regulators of stem cell behavior in ... genesdev.cshlp.org Genes & Development 9 facts

claimα-ketoglutarate (αKG) acts as a cosubstrate for αKG-dependent dioxygenases, a class of enzymes that serve as histone and DNA demethylases and can enact changes in nuclear gene expression.

claimSuccinate, which is the immediate downstream metabolite of alpha-ketoglutarate (αKG) in the TCA cycle, can competitively inhibit αKG-dependent dioxygenases and antagonize the effects of αKG.

claimThe accumulation or reduction of alpha-ketoglutarate (αKG) in the nucleocytosolic compartment is potentially mediated by transaminases or the mitochondrial alpha-ketoglutarate/malate carrier protein (SLC25A11).

claimMaintenance of increased total alpha-ketoglutarate (αKG):succinate pools maintains pluripotency in mouse embryonic stem cells.

claimThe enzyme branched chain amino transaminase 1 (BCAT1) modulates stem cell function by converting branched-chain amino acids (BCAAs) to branched-chain ketoacids through the transamination of α-ketoglutarate (αKG) to glutamate.

claimActivation or suppression of the serine biosynthesis pathway alters alpha-ketoglutarate (αKG) levels by modulating the activity of phosphoserine aminotransferase (PSAT1).

claimLeukemia cells up-regulate the enzyme BCAT1, which depletes alpha-ketoglutarate (αKG), resulting in the inhibition of ten-eleven translocation (Tet) DNA demethylases and subsequent DNA hypermethylation.

claimTransaminases including phosphoserine aminotransferase (PSAT1), alanine aminotransferase (GPT1/2), and aspartate aminotransferase (GOT1/2) contribute to the cytosolic accumulation or depletion of alpha-ketoglutarate (αKG).

claimAlpha-ketoglutarate (αKG) accumulation acts as a prodifferentiation factor in several tissue types, including premalignant epidermal stem cells, intestinal stem cells, and pancreatic cancer cells.

Mitochondria and the dynamic control of stem cell homeostasis link.springer.com Springer Apr 16, 2018 9 facts

claimTricarboxylic intermediates can be derived from both glucose and glutamine, with glutamine being converted into glutamate and subsequently into alpha-ketoglutarate (aKG) in the cytoplasm.

referenceHwang I-Y et al. reported in 2016 that Psat1-dependent fluctuations in α-ketoglutarate affect the timing of embryonic stem cell (ESC) differentiation.

referenceTeSlaa T et al. found in 2016 that α-ketoglutarate accelerates the initial differentiation of primed human pluripotent stem cells.

claimAlpha-ketoglutarate (aKG) enters the nucleus to serve as a substrate for ten-eleven translocation (TET) proteins for DNA methylation and for Jumonji C domain demethylase (JHDMs) for histone demethylation.

claimIn primed pluripotent stem cells (PSCs), alpha-ketoglutarate (aKG) has been found to both accelerate differentiation and support the undifferentiated state, suggesting it exerts opposite effects depending on the cellular context.

claimAlpha-ketoglutarate (aKG)-dependent DNA and histone methylation may promote naïve pluripotency.

claimAlpha-ketoglutarate (aKG) is transported into the cytosol via the aKG-malate shuttle, which also facilitates the transfer of NAD+/NADH between the mitochondria and the cytosol.

referenceCarey BW et al. demonstrated in 2014 that intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells.

claimAlpha-ketoglutarate (aKG) can function in the cytoplasm or be transferred into the mitochondria.