Activation of PPAR[alpha] suppresses anaplerosis from glutamine, by repressing the expression of glutaminase and glutamate dehydrogenase, thus potentially counteracting c-myc-dependent activation of glutaminolysis in tumor [97].
Therefore, the transrepression activity of PPAR[alpha] on lipid biosynthesis and anaplerosis is just as relevant as its transactivation activity on FAO genes.
AMPD deficiency does not seem to affect either TCA or glycolysis by anaplerosis upon exercise invivo.
However, a similar production of intermediates of the TCA during incremental cycle ergometry exercise upon exhaustion was found in homozygotes (TT), heterozygotes (CT), and wildtype (CC) for the c.34C>T mutation [6] suggesting that AMPD does not affect TCA anaplerosis. In addition, N[H.sub.3] has been proposed in in-vitro studies as a positive effector of glycogenolysis [1].
This results in an increased conversion of glutamate to a ketoglutarate and, thus, an increased flux of oxidative substrate into the mitochondria (
anaplerosis).
As for anaplerosis propagating the TCA cycle, it is a role typically filled by conversion of pyruvate to oxaloacetate (major reaction involving formation of HC[O.sub.3.sup.-]) and the reversible transamination of aspartate to form oxaloacetate (including generation of glutamate and depletion of aKG) coupled with the oxidation of glutamate back to aKG (glutamate + NA[D.sup.+] + [H.sub.2]O [right arrow] N[H.sub.4.sup.+] + aKG + NADH + [H.sup.+]) or the conversion of propionyl-CoA to succinyl-CoA (propionyl-CoA + ATP + HC[O.sub.3.sup.-] [right arrow] succinyl-CoA + ADP + [P.sub.i]) in the [beta]-oxidation of fatty acids [36].
If true, as will be discussed in a subsequent section of the paper, serine biosynthesis would play an important role in anaplerosis of glutamine-derived carbon to the TCA.
Prentki, "Glucose-regulated
anaplerosis and cataplerosis in pancreatic [beta] cells: possible implication of a pyruvate/citrate shuttle in insulin secretion," Diabetes, vol.
Other highly proliferative cell types, including tumour cells, use glutaminolysis to recycle NADPH for antioxidant reduction, fatty acid and nucleotide biosynthesis, and
anaplerosis (synthesis of TCA cycle intermediates), while glucose-derived carbon is used for macromolecule synthesis [92].
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anaplerosis o ampliacion del exiguo cuerpo civico con nuevos ciudadanos (Plb.
Tumor cells frequently show increased uptake of glutamine that provides nitrogen for protein and nucleotide synthesis, activate the regulator of protein translation mammalian target of rapamycin (mTOR), and provide intermediates of the tricarboxylic acid (TCA) cycle through
anaplerosis for biosynthetic pathways [76].
