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 mitochondrion for processing through part of the Krebs 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 isocitrate. 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]
^Pongratz RL, Kibbey RG, Cline GW (2009). "Chapter 24 Investigating the Roles of Mitochondrial and Cytosolic Malic Enzyme in Insulin Secretion". Mitochondrial Function, Part B: Mitochondrial Protein Kinases, Protein Phosphatases and Mitochondrial Diseases. Methods in Enzymology. Vol. 457. pp. 425–50.
doi:
10.1016/S0076-6879(09)05024-1.
ISBN978-0-12-374622-1.
PMC4422111.
PMID19426882.
Thompson SN (August 2004). "Dietary fat mediates hyperglycemia and the glucogenic response to increased protein consumption in an insect, Manduca sexta L". Biochimica et Biophysica Acta (BBA) - General Subjects. 1673 (3): 208–16.
doi:
10.1016/j.bbagen.2004.05.002.
PMID15279893.
Jin ES, Jones JG, Merritt M, Burgess SC, Malloy CR, Sherry AD (April 2004). "Glucose production, gluconeogenesis, and hepatic tricarboxylic acid cycle fluxes measured by nuclear magnetic resonance analysis of a single glucose derivative". Analytical Biochemistry. 327 (2): 149–55.
doi:
10.1016/j.ab.2003.12.036.
hdl:10316/3869.
PMID15051530.
She P, Burgess SC, Shiota M, et al. (July 2003). "Mechanisms by which liver-specific PEPCK knockout mice preserve euglycemia during starvation". Diabetes. 52 (7): 1649–54.
doi:
10.2337/diabetes.52.7.1649.
PMID12829628.
Thompson SN, Borchardt DB, Wang LW (March 2003). "Dietary nutrient levels regulate protein and carbohydrate intake, gluconeogenic/glycolytic flux and blood trehalose level in the insect Manduca sexta L". Journal of Comparative Physiology B. 173 (2): 149–63.
doi:
10.1007/s00360-002-0322-8.
PMID12624653.
S2CID21527819.
Thompson SN, Redak RA, Borchardt DB (June 2002). "The glucogenic response of a parasitized insect Manduca sexta L. is partially mediated by differential nutrient intake". Biochimica et Biophysica Acta (BBA) - General Subjects. 1571 (2): 138–50.
doi:
10.1016/S0304-4165(02)00208-8.
PMID12049794.
Thompson SN (February 2001). "Parasitism enhances the induction of glucogenesis by the insect, Manduca sexta L". The International Journal of Biochemistry & Cell Biology. 33 (2): 163–73.
doi:
10.1016/S1357-2725(00)00079-0.
PMID11240373.
Thompson SN (August 2000). "Pyruvate cycling and implications for regulation of gluconeogenesis in the insect, Manduca sexta L". Biochemical and Biophysical Research Communications. 274 (3): 787–93.
doi:
10.1006/bbrc.2000.3238.
PMID10924355.
Tosh D, Beresford G, Agius L (November 1994). "Glycogen synthesis from glucose by direct and indirect pathways in hepatocyte cultures from different nutritional states". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1224 (2): 205–12.
doi:
10.1016/0167-4889(94)90192-9.
PMID7981234.
Kunz WS, Davis EJ (January 1991). "Control of reversible intracellular transfer of reducing potential". Archives of Biochemistry and Biophysics. 284 (1): 40–6.
doi:
10.1016/0003-9861(91)90260-P.
PMID1824912.
Rognstad R (August 1979). "Pyruvate cycling involving possible oxaloacetate decarboxylase activity". Biochimica et Biophysica Acta (BBA) - General Subjects. 586 (2): 242–9.
doi:
10.1016/0304-4165(79)90096-5.
PMID476141.
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 mitochondrion for processing through part of the Krebs 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 isocitrate. 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]
^Pongratz RL, Kibbey RG, Cline GW (2009). "Chapter 24 Investigating the Roles of Mitochondrial and Cytosolic Malic Enzyme in Insulin Secretion". Mitochondrial Function, Part B: Mitochondrial Protein Kinases, Protein Phosphatases and Mitochondrial Diseases. Methods in Enzymology. Vol. 457. pp. 425–50.
doi:
10.1016/S0076-6879(09)05024-1.
ISBN978-0-12-374622-1.
PMC4422111.
PMID19426882.
Thompson SN (August 2004). "Dietary fat mediates hyperglycemia and the glucogenic response to increased protein consumption in an insect, Manduca sexta L". Biochimica et Biophysica Acta (BBA) - General Subjects. 1673 (3): 208–16.
doi:
10.1016/j.bbagen.2004.05.002.
PMID15279893.
Jin ES, Jones JG, Merritt M, Burgess SC, Malloy CR, Sherry AD (April 2004). "Glucose production, gluconeogenesis, and hepatic tricarboxylic acid cycle fluxes measured by nuclear magnetic resonance analysis of a single glucose derivative". Analytical Biochemistry. 327 (2): 149–55.
doi:
10.1016/j.ab.2003.12.036.
hdl:10316/3869.
PMID15051530.
She P, Burgess SC, Shiota M, et al. (July 2003). "Mechanisms by which liver-specific PEPCK knockout mice preserve euglycemia during starvation". Diabetes. 52 (7): 1649–54.
doi:
10.2337/diabetes.52.7.1649.
PMID12829628.
Thompson SN, Borchardt DB, Wang LW (March 2003). "Dietary nutrient levels regulate protein and carbohydrate intake, gluconeogenic/glycolytic flux and blood trehalose level in the insect Manduca sexta L". Journal of Comparative Physiology B. 173 (2): 149–63.
doi:
10.1007/s00360-002-0322-8.
PMID12624653.
S2CID21527819.
Thompson SN, Redak RA, Borchardt DB (June 2002). "The glucogenic response of a parasitized insect Manduca sexta L. is partially mediated by differential nutrient intake". Biochimica et Biophysica Acta (BBA) - General Subjects. 1571 (2): 138–50.
doi:
10.1016/S0304-4165(02)00208-8.
PMID12049794.
Thompson SN (February 2001). "Parasitism enhances the induction of glucogenesis by the insect, Manduca sexta L". The International Journal of Biochemistry & Cell Biology. 33 (2): 163–73.
doi:
10.1016/S1357-2725(00)00079-0.
PMID11240373.
Thompson SN (August 2000). "Pyruvate cycling and implications for regulation of gluconeogenesis in the insect, Manduca sexta L". Biochemical and Biophysical Research Communications. 274 (3): 787–93.
doi:
10.1006/bbrc.2000.3238.
PMID10924355.
Tosh D, Beresford G, Agius L (November 1994). "Glycogen synthesis from glucose by direct and indirect pathways in hepatocyte cultures from different nutritional states". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1224 (2): 205–12.
doi:
10.1016/0167-4889(94)90192-9.
PMID7981234.
Kunz WS, Davis EJ (January 1991). "Control of reversible intracellular transfer of reducing potential". Archives of Biochemistry and Biophysics. 284 (1): 40–6.
doi:
10.1016/0003-9861(91)90260-P.
PMID1824912.
Rognstad R (August 1979). "Pyruvate cycling involving possible oxaloacetate decarboxylase activity". Biochimica et Biophysica Acta (BBA) - General Subjects. 586 (2): 242–9.
doi:
10.1016/0304-4165(79)90096-5.
PMID476141.