The effects of α-adrenergic stimulation on the regulation of the pyruvate dehydrogenase complex in the perfused rat liver

Rory A Fisher; Shunichi Tanabe; Denis B Buxton; Merle S Olson

doi:10.1016/S0021-9258(17)39356-0

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The effects of α-adrenergic stimulation on the regulation of the pyruvate dehydrogenase complex in the perfused rat liver

Journal article

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The effects of α-adrenergic stimulation on the regulation of the pyruvate dehydrogenase complex in the perfused rat liver

Rory A Fisher, Shunichi Tanabe, Denis B Buxton and Merle S Olson

The Journal of biological chemistry, Vol.260(16), pp.9223-9229

1985

DOI: 10.1016/S0021-9258(17)39356-0

PMID: 2991237

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Abstract

The regulation of the pyruvate dehydrogenase multienzyme complex was investigated during alpha-adrenergic stimulation with phenylephrine in the isolated perfused rat liver. The metabolic flux through the pyruvate dehydrogenase reaction was monitored by measuring the production of 14CO2 from infused [1-14C] pyruvate. In livers from fed animals perfused with a low concentration of pyruvate (0.05 mM), phenylephrine infusion significantly inhibited the rate of pyruvate decarboxylation without affecting the amount of pyruvate dehydrogenase in its active form. Also, phenylephrine caused no significant effect on tissue NADH/NAD+ and acetyl-CoA/CoASH ratios or on the kinetics of pyruvate decarboxylation in 14CO2 washout experiments. Phenylephrine inhibition of [1-14C]pyruvate decarboxylation was, however, closely associated with a decrease in the specific radioactivity of perfusate lactate, suggesting that the pyruvate decarboxylation response simply reflected dilution of the labeled pyruvate pool due to phenylephrine-stimulated glycogenolysis. This suggestion was confirmed in additional experiments which showed that the alpha-adrenergic-mediated inhibitory effect on pyruvate decarboxylation was reduced in livers perfused with a high concentration of pyruvate (1 mM) and was absent in livers from starved rats. Thus, alpha-adrenergic agonists do not exert short term regulatory effects on pyruvate dehydrogenase in the liver. Furthermore, the results suggest either that the rat liver pyruvate dehydrogenase complex is insensitive to changes in mitochondrial calcium or that changes in intramitochondrial calcium levels as a result of alpha-adrenergic stimulation are considerably less than suggested by others.

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Title: Subtitle: The effects of α-adrenergic stimulation on the regulation of the pyruvate dehydrogenase complex in the perfused rat liver
Creators: Rory A Fisher - Univ. Texas, health sci. center
Shunichi Tanabe - Univ. Texas, health sci. center
Denis B Buxton - Univ. Texas, health sci. center
Merle S Olson - Univ. Texas, health sci. center
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.260(16), pp.9223-9229
DOI: 10.1016/S0021-9258(17)39356-0
PMID: 2991237
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; Bethesda, MD
Language: English
Date published: 1985
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040593902771

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