Pyruvate cycling

Pyruvate cycling commonly refers to an intracellular loop of spatial movements and chemical transformations involving pyruvate. Spatial movements occur between mitochondria and cytosol and chemical transformations create various Krebs cycle intermediates. In all variants, pyruvate is imported into the mitochnodrion for processing through part of the Krebb's cycle. In addition to pyruvate, alpha-ketoglutarate may also be imported. At various points, the intermediate product is exported to the cytosol for additional transformations and then re-imported. Three specific pyruvate cycles are generally considered,[1] each named for the principal molecule exported from the mitochondrion: malate, citrate, and iso-citrate.Other variants may exist, such as dissipative or "futile" pyruvate cycles.[2][3]

This cycle is usually studied in relation to Glucose Stimulated Insulin Secretion ( or GSIS ) and there is thought to be a relationship between the insulin response and NADPH produced from this cycle[4][5] but the specifics are not clear and particular confusion exists about the role of malic enzymes.[6][7] It has been observed in various cell types including islet cells.

The pyruvate-malate cycle was described in liver and kidney preparations as early as 1971.[8]


References

  1. Ronnebaum SM, Ilkayeva O, Burgess SC, et al. (October 2006). "A pyruvate cycling pathway involving cytosolic NADP-dependent isocitrate dehydrogenase regulates glucose-stimulated insulin secretion". The Journal of Biological Chemistry. 281 (41): 30593–602. doi:10.1074/jbc.M511908200. PMID 16912049.
  2. Gregory RB, Berry MN (May 1992). "Stimulation by thyroid hormone of coupled respiration and of respiration apparently not coupled to the synthesis of ATP in rat hepatocytes". The Journal of Biological Chemistry. 267 (13): 8903–8. PMID 1577728.
  3. Agius L, Tosh D, Peak M (January 1993). "The contribution of pyruvate cycling to loss of 6-3Hglucose during conversion of glucose to glycogen in hepatocytes: effects of insulin, glucose and acinar origin of hepatocytes". The Biochemical Journal. 289 (Pt 1): 255–62. PMC 1132158Freely accessible. PMID 8380985.
  4. Pongratz RL, Kibbey RG, Cline GW (2009). "Investigating the roles of mitochondrial and cytosolic malic enzyme in insulin secretion". Methods in Enzymology. Methods in Enzymology. 457: 425–50. doi:10.1016/S0076-6879(09)05024-1. ISBN 978-0-12-374622-1. PMID 19426882.
  5. Guay C, Madiraju SR, Aumais A, Joly E, Prentki M (December 2007). "A role for ATP-citrate lyase, malic enzyme, and pyruvate/citrate cycling in glucose-induced insulin secretion". The Journal of Biological Chemistry. 282 (49): 35657–65. doi:10.1074/jbc.M707294200. PMID 17928289.
  6. Ronnebaum SM, Jensen MV, Hohmeier HE, et al. (October 2008). "Silencing of Cytosolic or Mitochondrial Isoforms of Malic Enzyme Has No Effect on Glucose-stimulated Insulin Secretion from Rodent Islets". The Journal of Biological Chemistry. 283 (43): 28909–17. doi:10.1074/jbc.M804665200. PMC 2570884Freely accessible. PMID 18755687.
  7. Heart E, Cline GW, Collis LP, Pongratz RL, Gray JP, Smith PJ (June 2009). "Role for malic enzyme, pyruvate carboxylation, and mitochondrial malate import in glucose-stimulated insulin secretion". American Journal of Physiology. Endocrinology and Metabolism. 296 (6): E1354–62. doi:10.1152/ajpendo.90836.2008. PMC 2692397Freely accessible. PMID 19293334.
  8. Scaduto RC, Davis EJ (August 1986). "The involvement of pyruvate cycling in the metabolism of aspartate and glycerate by the perfused rat kidney". The Biochemical Journal. 237 (3): 691–8. PMC 1147046Freely accessible. PMID 3800911.

Further reading

External links

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