Home LiteratureArticle Details
PMID: 3814076 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Kinase activator protein mediates longer-term effects of starvation on activity of pyruvate dehydrogenase kinase in rat liver mitochondria.

The Biochemical journal ·Vol. 239 ·No. 2 ·1986-10-15 ·Pages 347-54

Denyer GS, Kerbey AL, Randle PJ

Abstract

Starvation of rats for 48 h increased the activity of PDH (pyruvate dehydrogenase) kinase 2.2-fold in extracts of liver mitochondria, 2.9-fold in PDH complex partially purified therefrom by fractional precipitation, and 5-fold in PDH complex partially purified by gel filtration on Sephacryl S-300. A protein fraction was separated from PDH complex in extracts of rat liver mitochondria by gel filtration or fractional precipitation, which increased the activity of PDH kinase in rat liver and pig heart PDH complexes. The activity of this protein fraction was increased approx. 2.5-fold by 48 h starvation of rats. With highly purified pig heart PDH complex it was shown that the protein fraction increased the Vmax. of the PDH kinase reaction 35-fold (fraction from fed rats) or 82-fold (fraction from starved rats); starvation had no effect on the concentration of protein fraction required to give 0.5 Vmax. Evidence is given that the increase in PDH kinase activity effected in extracts of liver mitochondria by starvation is due to increased activity of kinase activator protein, which is tightly bound by rat liver PDH complex and not removed by a single gel filtration. With pig heart PDH complex, increased PDH kinase activity was retained after gel filtration of an admixture with kinase activator protein from starved rats, but was restored to the control value by a second gel filtration; the alterations in PDH kinase activity were associated with obvious changes in protein bands in SDS gels.

MeSH Terms
Animals Electrophoresis, Polyacrylamide Gel Enzyme Activation/drug effects Heart/drug effects Male Mitochondria, Liver/drug effects,enzymology Myocardium/enzymology Phosphorylation Protein Kinases/metabolism Protein Serine-Threonine Kinases Proteins/pharmacology Pyruvate Dehydrogenase Acetyl-Transferring Kinase Rats Rats, Inbred Strains Starvation/enzymology
Chemicals
Proteins Pyruvate Dehydrogenase Acetyl-Transferring Kinase Protein Kinases Protein Serine-Threonine Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Denyer G S
Kerbey A L
Randle P J
References (40)
40 references, click to expand
  1. Alpha-keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation.
    Proc Natl Acad Sci U S A. 1969 Jan;62(1):234-41 PMID: 4306045
  2. Regulation of flux through pyruvate dehydrogenase and pyruvate carboxylase in rat hepatocytes. Effects of fatty acids and glucagon.
    Eur J Biochem. 1985 Nov 4;152(3):699-707 PMID: 3932072
  3. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  4. Stimulation by calcium ions of pyruvate dehydrogenase phosphate phosphatase.
    Biochem J. 1972 Jun;128(1):161-3 PMID: 4343661
  5. Regulation of the mammalian pyruvate dehydrogenase complex by covalent modification.
    Symp Soc Exp Biol. 1973;27:371-400 PMID: 4271940
  6. Regulation of heart muscle pyruvate dehydrogenase kinase.
    Biochem J. 1974 Dec;143(3):625-41 PMID: 4462746
  7. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
    Anal Biochem. 1976 May 7;72:248-54 PMID: 942051
  8. Diabetes and the control of pyruvate dehydrogenase in rat heart mitochondria by concentration ratios of adenosine triphosphate/adenosine diphosphate, of reduced/oxidized nicotinamide-adenine dinucleotide and of acetyl-coenzyme A/coenzyme A.
    Biochem J. 1977 Jun 15;164(3):509-19 PMID: 196589
  9. Phosphorylation of additional sites on pyruvate dehydrogenase inhibits its re-activation by pyruvate dehydrogenase phosphate phosphatase.
    Biochem J. 1978 Feb 1;169(2):433-5 PMID: 204298
  10. Studies on the relationship between ketogenesis and pyruvate oxidation in isolated rat liver mitochondria.
    J Biol Chem. 1978 Apr 10;253(7):2229-37 PMID: 632266
  11. The effect of fatty acids on the regulation of pyruvate dehydrogenase in perfused rat liver.
    Eur J Biochem. 1978 May 16;86(2):519-30 PMID: 658055
  12. Enhanced activity of pyruvate dehydrogenase kinase in rat heart mitochondria in alloxan-diabetes or starvation.
    FEBS Lett. 1978 Aug 1;92(1):73-6 PMID: 668923
  13. Sites of phosphorylation on pyruvate dehydrogenase from bovine kidney and heart.
    Biochemistry. 1978 Jun 13;17(12):2364-70 PMID: 678513
  14. The mode of regulation of pyruvate dehydrogenase of lactating rat mammary gland. Effects of starvation and insulin.
    Biochem J. 1978 Aug 15;174(2):553-61 PMID: 213055
  15. Amino acid sequences around the sites of phosphorylation in the pig heart pyruvate dehydrogenase complex.
    Biochem J. 1979 Aug 1;181(2):419-26 PMID: 496891
  16. Regulation of kinase reactions in pig heart pyruvate dehydrogenase complex.
    Biochem J. 1979 Aug 1;181(2):427-33 PMID: 227365
  17. Thermolabile factor accelerates pyruvate dehydrogenase kinase reaction in heart mitochondria of starved or alloxan-diabetic rats.
    FEBS Lett. 1981 May 18;127(2):188-92 PMID: 7238878
  18. Analysis of site occupancies in [32P]phosphorylated pyruvate dehydrogenase complexes by aspartyl-prolyl cleavage of tryptic phosphopeptides.
    Eur J Biochem. 1981 Dec;120(3):535-40 PMID: 7333279
  19. Role of pyruvate transporter in the regulation of the pyruvate dehydrogenase multienzyme complex in perfused rat liver.
    Biochemistry. 1982 Jan 19;21(2):346-53 PMID: 7074018
  20. Role of individual phosphorylation sites in inactivation of pyruvate dehydrogenase complex in rat heart mitochondria.
    Biochem J. 1982 Apr 1;203(1):99-108 PMID: 7103952
  21. Assay of cyclic AMP-dependent protein kinases.
    Methods Enzymol. 1974;38:287-90 PMID: 4375761
  22. Pyruvate dehydrogenase kinase/activator in rat heart mitochondria, Assay, effect of starvation, and effect of protein-synthesis inhibitors of starvation.
    Biochem J. 1982 Jul 15;206(1):103-11 PMID: 7126186
  23. Occupancy of phosphorylation sites in pyruvate dehydrogenase phosphate complex in rat heart in vivo. Relation to proportion of inactive complex and rate of re-activation by phosphatase.
    Biochem J. 1982 Aug 15;206(2):221-9 PMID: 6293460
  24. Purification and properties of pyruvate dehydrogenase phosphatase from bovine heart and kidney.
    Biochemistry. 1982 Oct 26;21(22):5585-92 PMID: 6293549
  25. Essential role of coenzyme A in pyruvate dehydrogenase kinase activity.
    FEBS Lett. 1982 Nov 8;148(2):201-6 PMID: 7152017
  26. Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats.
    Biochem J. 1982 Oct 15;208(1):53-60 PMID: 7159398
  27. Pyruvate dehydrogenase kinase activity of pig heart pyruvate dehydrogenase (E1 component of pyruvate dehydrogenase complex).
    Biochem J. 1985 Nov 1;231(3):523-9 PMID: 3840997
  28. Studies on the activation of rat liver pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase by adrenaline and glucagon. Role of increases in intramitochondrial Ca2+ concentration.
    Biochem J. 1985 Nov 1;231(3):597-608 PMID: 3935105
  29. Modulation of pyruvate dehydrogenase kinase activity in cultured hepatocytes by glucagon and n-octanoate.
    Biochem J. 1986 Feb 15;234(1):233-6 PMID: 3707545
  30. Fuel selection in animals.
    Biochem Soc Trans. 1986 Oct;14(5):799-806 PMID: 3536635
  31. Effects of low-protein diet and starvation on the activity of branched-chain 2-oxo acid dehydrogenase kinase in rat liver and heart.
    Biochem J. 1986 Jul 1;237(1):285-8 PMID: 3800883
  32. Statistical estimations in enzyme kinetics.
    Biochem J. 1961 Aug;80:324-32 PMID: 13785321
  33. The mammalian pyruvate dehydrogenase complex: structure and regulation.
    Rev Physiol Biochem Pharmacol. 1983;96:123-70 PMID: 6338572
  34. Purification and properties of pyruvate dehydrogenase kinase from bovine kidney.
    J Biol Chem. 1983 Aug 10;258(15):9454-8 PMID: 6348044
  35. Reversible phosphorylation of pyruvate dehydrogenase in rat skeletal-muscle mitochondria. Effects of starvation and diabetes.
    Biochem J. 1984 Apr 15;219(2):635-46 PMID: 6331393
  36. Effects of diet and of alloxan-diabetes on the activity of branched-chain 2-oxo acid dehydrogenase complex and of activator protein in rat tissues.
    Biochem J. 1984 Sep 15;222(3):711-9 PMID: 6487271
  37. The roles of intrinsic kinase and of kinase/activator protein in the enhanced phosphorylation of pyruvate dehydrogenase complex in starvation.
    FEBS Lett. 1984 Oct 15;176(1):115-9 PMID: 6489513
  38. Low immunogenicity of the common lipoamide dehydrogenase subunit (E3) of mammalian pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase multienzyme complexes.
    Biochem J. 1985 Mar 1;226(2):509-17 PMID: 3838892
  39. Modification of bovine kidney pyruvate dehydrogenase kinase activity by CoA esters and their mechanism of action.
    J Biol Chem. 1985 Aug 25;260(18):10146-52 PMID: 4019505
  40. Alpha-keto acid dehydrogenase complexes. XI. Comparative studies of regulatory properties of the pyruvate dehydrogenase complexes from kidney, heart, and liver mitochondria.
    Proc Natl Acad Sci U S A. 1969 Sep;64(1):227-34 PMID: 4312751
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2390347
Published
1986-10-15
Pages
347-54
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1147287
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2390347 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2