Abstract
Pyruvate dehydrogenase (PDH) is a key rate-limiting enzyme responsible for insulin-stimulated oxidative glucose metabolism. Insulin action leads to an increase in the dephosphorylated (active) form of the enzyme (Jungas, 1971; Linn, Pettit and Reed, 1969). MaCauley and Jarett (1985) demonstrated that the specific interconverting enzyme under insulin control was its phosphatase. They clearly demonstrated that a substance was produced when insulin interacted with plasma membranes which stimulated PDH phosphatase in mitochondria. Independently, Larner et al. (1979) presented evidence of an insulin-generated heat-stable factor(s) which inhibited cAMP-dependent protein kinase and which also stimulated crude glycogen synthase phosphatase. In 1979; Jarett and Seals (1979) reported that the factor(s) isolated in Larner’s laboratory could also stimulate PDH phosphatase. We then further separated from the original fraction by anion exchange, two separate fractions; one contained the cAMP-dependent protein kinase inhibitor, while the other contained the PDH phosphatase stimulator (Larner et al., 1988a, b). The former contained myo-inositol and glucosamine after acid hydrolysis; the latter contained D-chiro-inositol and galactosamine after acid hydrolysis.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Denton, R.M., Midgley, P.J.W., Rutter, G.A., Thomas, A.P. and Mc Cormack, J.G. (1989) Studies into the mechanism whereby insulin activates pyruvate dehydrogenase complex in adipose tissue. Ann. N.Y. Acad. Sci. 573: 285–296.
Farese, R.V., Standaert, M.L., Yamada, K., Huang, L.C., Zhang, C., Cooper, D.R., Wang, Z., Yang, Y., Suzuki, S., Toyota, T. and Lamer, J. (1994) Proc. Natl. Acad. Sci. USA 91: 11040–11044.
Huang, L.C., Fontelles, M.C., Houston, D.B., Zhang, C. and Larner, J. (1993) Acute glycogenic and hypoglycemic effects of two inositol-phosphoglycan insulin mediators in normal and streptozotocin-diabetic rats in vivo. Endocrinol 132: 652–657.
Jarett, L. and Seals, J.R. (1979) Pyruvate dehydrogenase activation in adipocyte mitochondria by an insulin-generated mediator from muscle. Science 206: 1406–1408.
Jungas, R.L. (1971) Hormonal regulation of pyruvate dehydrogenase. Metabolism 20: 43–53.
Larner, J., Galasko, G., Cheng, K., DePaoli, A.A., Huang, L., Daggy, P. and Kellogg, J. (1979) Generation by insulin of a chemical mediator that controls protein phosphorylation and dephosphorylation. Science 206: 1408–1410.
Larner, J., Huang, L.C., Schwartz, C.F.W., Oswald, A.S., Shen, T.-Y., Kinter, M., Tang, G. and Zeller, K. (1988a) Rat liver mediator which stimulates pyruvate dehydrogenase phosphatase contains galactosamine and D-chiro-inositol. Biochem. Biophys. Res. Comm. 151: 1416–1426.
Larner, J., Huang, L.C., Tang, G., Suzuki, S., Schwartz, C.F.W., Romero, G., Roulidis, Z., Zeller, K., Shen, T.-Y., Oswald, A.S. and Luttrell, L. (1988b) Insulin mediators: Structure and function. Cold Spring Harb. Symp. LIII 965–971.
Larner, J., Huang, L.C., Suzuki, S., Tang, G., Zhang, C., Schwartz, C.F.W., Romero, G., Luttrell, L. and Kennington, A.S. (1989) Insulin mediators and the control of pyruvate dehydrogenase complex. Ann. of N.Y. Acad. Sci. 573: 297–305.
Larner, J., Abe, S., Zhang, C., Rule, G., Price, J. and Huang, L.C. (1994) Action mechanisms and partial structures of insulin mediators–special poster session. Late-breaking topics. Am. Soc. Biochem. Molec. Biol., Washington, D.C.
Lawson, J.E., Niu, X.-D., Browning, K.S., Trong, H.L., Yan, J. and Reed, L.J. (1993) Molecular cloning and expression of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase and sequence similarity with protein phosphatase 2C. Biochem. 32: 8987–8993.
Linn, T.C., Pettit, F.H., and Reed, L.J. (1969) Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc. Natl. Acad. Sci. USA 62: 234–241.
MaCauley, S.L. and Jarett. L. (1985) Insulin mediator causes dephosphorylation of the a subunit of pyruvate dehydrogenase by stimulating phosphatase activity. Arch. Biochem. Biophys. 237: 142–150.
Mato, J.M., Kelly, K.L., Abler, A., Jarett, L., Corkey, B.E., Cashel, J.A. and Zopf, D. (1987) Partial structure of an insulin-sensitive phospholipid. Biochem. Biophys. Res. Comm. 146: 764–770.
Nestler, J.E., Romero, G., Huang, L.C., Zhang, C. and Larner, J. (1991) Insulin mediators are the signal transduction system responsible for insulin’s actions on human placental steroidogenesis. Endocrinol. 129: 2951–2956.
Romero, G., Luttrell, L., Rogol, A., Zeller, K., Hewlett, E. and Larner, J. (1988) Phosphatidylinositol-glycan anchors of membrane proteins: Potential precursors for insulin mediators. Science 240: 509–511.
Romero, G., Games, G., Huang, L.C., Lilley, K. and Luttrell, L. (1990) Anti-inositol glycan antibodies selectively block some of the action of insulin in intact BC3H1 cells. Proc. Natl. Acad. Sci. 88: 1476–1480.
Saltiel, A.R. and Cuatrecassas, P. (1986) Insulin stimulates the generation from hepatic plasma membranes of modulators derived from an inositol glycolipid. Proc. Natl. Acad. Sci. USA 83: 5793–5797.
Tamura, S., Lynch, K.R., Fox, J., Yasui, A., Kikuchi, K., Suzuki, Y. and Tsuiki, S. (1989) Molecular cloning of rat type 2C (1A) protein phosphatase mRNA. Proc. Natl. Acad. Sci. USA 86: 1796–1800.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Birkhäuser Verlag Basel/Switzerland
About this chapter
Cite this chapter
Abe, S., Huang, L.C., Larner, J. (1996). Dephosphorylation of PDH by phosphoprotein phosphatases and its allosteric regulation by inositol glycans. In: Patel, M.S., Roche, T.E., Harris, R.A. (eds) Alpha-Keto Acid Dehydrogenase Complexes. MCBU Molecular and Cell Biology Updates. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-8981-0_14
Download citation
DOI: https://doi.org/10.1007/978-3-0348-8981-0_14
Publisher Name: Birkhäuser Basel
Print ISBN: 978-3-0348-9853-9
Online ISBN: 978-3-0348-8981-0
eBook Packages: Springer Book Archive