Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex

Melissa M. Bowker-Kinley, Wilhelmina I. Davis, Pengfei Wu, Robert Harris, Kirill M. Popov

Research output: Contribution to journalArticle

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Abstract

Tissue distribution and kinetic parameters for the four isoenzymes of pyruvate dehydrogenase kinase (PDK1, PDK2, PDK3 and PDK4) identified thus far in mammals were analysed. It appeared that expression of these isoenzymes occurs in a tissue-specific manner. The mRNA for isoenzyme PDK1 was found almost exclusively in rat heart. The mRNA for PDK3 was most abundantly expressed in rat testis. The message for PDK2 was present in all tissues tested but the level was low in spleen and lung. The mRNA for PDK4 was predominantly expressed in skeletal muscle and heart. The specific activities of the isoenzymes varied 25-fold, from 50 nmol/min per mg for PDK2 to 1250 nmol/min per mg for PDK3. Apparent K(i) values of the isoenzymes for the synthetic analogue of pyruvate, dichloroacetate, varied 40-fold, from 0.2 mM for PDK2 to 8 mM for PDK3. The isoenzymes were also different with respect to their ability to respond to NADH and NADH plus acetyl-CoA. NADH alone stimulated the activities of PDK1 and PDK2 by 20 and 30% respectively. NADH plus acetyl-CoA activated these isoenzymes nearly 200 and 300%. Under comparable conditions, isoenzyme PDK3 was almost completely unresponsive to NADH, and NADH plus acetyl-CoA caused inhibition rather than activation. Isoenzyme PDK4 was activated almost 2-fold by NADH, but NADH plus acetyl-CoA did not activate above the level seen with NADH alone. These results provide the first evidence that the unique tissue distribution and kinetic characteristics of the isoenzymes of PDK are among the major factors responsible for tissue-specific regulation of the pyruvate dehydrogenase complex activity.

Original languageEnglish
Pages (from-to)191-196
Number of pages6
JournalBiochemical Journal
Volume329
Issue number1
StatePublished - Jan 1 1998

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Pyruvate Dehydrogenase Complex
Isoenzymes
NAD
Tissue
Acetyl Coenzyme A
Tissue Distribution
Messenger RNA
Rats
Mammals
Thromboplastin
Pyruvic Acid
Kinetic parameters
Muscle
Testis
Skeletal Muscle
Spleen
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Bowker-Kinley, M. M., Davis, W. I., Wu, P., Harris, R., & Popov, K. M. (1998). Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. Biochemical Journal, 329(1), 191-196.

Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. / Bowker-Kinley, Melissa M.; Davis, Wilhelmina I.; Wu, Pengfei; Harris, Robert; Popov, Kirill M.

In: Biochemical Journal, Vol. 329, No. 1, 01.01.1998, p. 191-196.

Research output: Contribution to journalArticle

Bowker-Kinley, MM, Davis, WI, Wu, P, Harris, R & Popov, KM 1998, 'Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex', Biochemical Journal, vol. 329, no. 1, pp. 191-196.
Bowker-Kinley, Melissa M. ; Davis, Wilhelmina I. ; Wu, Pengfei ; Harris, Robert ; Popov, Kirill M. / Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. In: Biochemical Journal. 1998 ; Vol. 329, No. 1. pp. 191-196.
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