Review on PEPCK for the month of August, 2011 Phosphoenolpyruvate carboxykinase (PEPCK) activity and mRNA levels in Rubratoxin

B (a mycotoxin)- treated mice were reduced, indicating that Rubratoxin B causes hepatic glycogen depletion by inhibiting PEPCK (Iwashita et al, 2011). Reduced protein expression of PEPCK and HNF4 was demonstrated in rat hepatoma H4IIE cells incubated in the presence of oolong tea (Yasui et al, 2011). In hepatocyte, FGF-21 up-regulation reduces PEPCK mRNA expression, whereas down-regulation has the opposite effects (Li et al, 2011). Molecular studies showed a specific upregulation of the glutamine transporter SN1 is correlated with the upregulation of PEPCK. These effects were seen in potassium deficient diets (Abu et al, 2011). Onset of metabolic acidosis leads to a rapid and pronounced increase in expression of PEPCK in rat renal proximal convoluted tubules (Mufti et al, 2011). Though Tamoxifen (a selective estrogen receptor modulator) inhibits gluconeogenesis from both lactate and fructose at very low concentrations, it does not affect the most important key-enzymes of gluconeogenesis PEPCK (Marek et al, 2011). OATP1B (organic anion transporting polypeptides)-mediated hepatic thyroid hormone entry is a key determinant of cholesterol and glucose homeostasis. Loss of liver-specific Oatp1b2-mediated hepatocellular thyroid hormone entry, leads to reduced transcriptional activation PEPCK (Schwabedissen et al, 2011).

References: Iwashita K, Nagashima H. 2011. Rubratoxin B induces signs of fatty acid oxidation disorders (FAODs) in mice. Toxicol Lett. Yasui, K., Miyoshi, N., Tababe, H., Ishigami, Y., Fukutomi, R., Imai, S., Isemura, M. 2011. Effects of Oolong Tea on Gene Expression of Gluconeogenic Enzymes in the Mouse Liver and in Rat Hepatoma H4IIE Cells. J Med Food. Li, K., Li, L., Yang, M., Liu, H., Boden, G., Yang, G.2011. The effects of fibroblast growth factor-21 knockdown and over-expression on its signaling pathway and glucose-lipid metabolism in vitro. Mol Cell Endocrinol

Abu, H, S., Chaudhry, F, A., Zahedi, K, A., Siddiqui, F., Amlal, H.2011. Cellular and Molecular Basis of Increased Ammoniagenesis in Potassium Deprivation. Am J Physiol Renal Physiol. Mufti, J., Hajarnis, S., Shepardson, K., Gummadi, L., Taylor, L., Curthoys, N, P. 2011. Role of AUF1 and HuR in the pH-responsive stabilization of phosphoenolpyruvate

carboxykinase mRNA in LLC-PK1-F+ cells. Am J Physiol Renal Physiol. Marek, C, B., Peralta, R, M., Itinose, A, M., Bracht, A. 2011. Influence of tamoxifen on gluconeogenesis and glycolysis in the perfused rat liver. Chem Biol Interact. 193; 22-33. Schwabedissen, H, E., Ware, J, A., Finkelstein, D., Chaudhry, A, S., Mansell, S., Leon-Ponte, M., Strom, S, C., Zaher, H., Schwarz, U, I., Freeman, D, J., Schuetz, E, G., Tirona, R, G., Kim, R, B. 2011. Hepatic organic anion transporting polypeptide transporter and thyroid hormone receptor interplay determines cholesterol and glucose homeostasis. Hepatology. 54:644-54.