Ciclo do piruvato

O ciclo do piruvato xeralmente refírese aos movementos entre distintos compartimentos celulares e transformacións químicas que sofre o piruvato. Os movementos espaciais dentro da célula do piruvato ocorren entre as mitocondrias e o citosol e as transformacións químicas orixinan varios intermediarios do ciclo de Krebs. En todas as variantes, o piruvato impórtase á mitocondria para ser procesado introducindo os seus carbonos (en forma de acetil-CoA) no ciclo de Krebs. Ademais do piruvato, pode importarse tamén alfa-cetoglutarato. En varios puntos, o produto intermediario é exportado ao citosol para que sufra alí transformacións adicionais e despois reimportado. Xeralmente considéranse tres ciclos do piruvato específicos,^[1] cada un denominado pola principal molécula exportada desde a mitocondria: malato, citrato, e isocitrato. Poden existir outras variantes, como os ciclos fútiles ou disipativos do piruvato.^[2]^[3]

Este ciclo estúdase xeralmente en relación á secreción de insulina estimulada por glicosa (ou GSIS) e crese que hai unha relación entre a resposta á insulina e o NADPH producido neste ciclo,^[4]^[5] pero os detalles específicos non están claros e existe unha certa confusión sobre o papel dos encimas málicos.^[6]^[7] O fenómeno foi obsevada nas células dos illotes pancreáticos.

O ciclo do piruvato-malato foi descrito no fígado e preparacións de ril xa en 1971.^[8]

Notas

↑ Ronnebaum SM, Ilkayeva O, Burgess SC; et al. (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. PMID 16912049. doi:10.1074/jbc.M511908200.
↑ Gregory RB, Berry MN (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. Arquivado dende o orixinal o 28 de maio de 2020. Consultado o 09 de xaneiro de 2014.
↑ Agius L, Tosh D, Peak M (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 1132158. PMID 8380985.
↑ 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. ISBN 978-0-12-374622-1. PMID 19426882. doi:10.1016/S0076-6879(09)05024-1.
↑ Guay C, Madiraju SR, Aumais A, Joly E, Prentki M (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. PMID 17928289. doi:10.1074/jbc.M707294200.
↑ Ronnebaum SM, Jensen MV, Hohmeier HE; et al. (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. PMC 2570884. PMID 18755687. doi:10.1074/jbc.M804665200.
↑ Heart E, Cline GW, Collis LP, Pongratz RL, Gray JP, Smith PJ (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. PMC 2692397. PMID 19293334. doi:10.1152/ajpendo.90836.2008.
↑ Scaduto RC, Davis EJ (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 1147046. PMID 3800911.

Véxase tamén

Bibliografía

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Ligazóns externas

"FIGURE 2: Biochemical mechanisms of glucose-stimulated insulin secretion, including roles of the pyrvuate cycling pathways of the β-cell". from Muoio, Deborah M.; Newgard, Christopher B. (2008). "Mechanisms of disease: Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes". Nature Reviews Molecular Cell Biology 9 (3): 193–205. PMID 18200017. doi:10.1038/nrm2327.

[1] Ronnebaum SM, Ilkayeva O, Burgess SC; et al. (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. PMID 16912049. doi:10.1074/jbc.M511908200.

[2] Gregory RB, Berry MN (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. Arquivado dende o orixinal o 28 de maio de 2020. Consultado o 09 de xaneiro de 2014.

[3] Agius L, Tosh D, Peak M (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 1132158. 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. ISBN 978-0-12-374622-1. PMID 19426882. doi:10.1016/S0076-6879(09)05024-1.

[5] Guay C, Madiraju SR, Aumais A, Joly E, Prentki M (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. PMID 17928289. doi:10.1074/jbc.M707294200.

[6] Ronnebaum SM, Jensen MV, Hohmeier HE; et al. (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. PMC 2570884. PMID 18755687. doi:10.1074/jbc.M804665200.

[7] Heart E, Cline GW, Collis LP, Pongratz RL, Gray JP, Smith PJ (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. PMC 2692397. PMID 19293334. doi:10.1152/ajpendo.90836.2008.

[8] Scaduto RC, Davis EJ (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 1147046. PMID 3800911.

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