| Regulation of pyruvate dehydrogenase in isolated rat liver mitochondria. Effects of octanoate, oxidation-reduction state, and adenosine triphosphate to adenosine diphosphate ratio. | |
| | |
MedLine Citation:
|
PMID: 1116996 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Factors which influence the distribution of pyruvate dehydrogenase between its active, unphosphorylated form (PDHa) and its inactive, phosphorylated form (PDHb) have been examined in isolated rat liver mitochondria. A rapid freezing method was developed for the extraction of pyruvate dehydrogenase from incubated mitochondria which prevented interconversions between PHDa and PDHb which normally occur when mitochondria are collected by centrifugal methods. The intramitochondrial ATP:ADP ration was varied over a 100-fold range by the addition of dinitrophenol, oligomycin, or both substances to mitochondria oxidizing 2-oxoglutarate. PDHa activity was found to be inversely proportional to the intramitochondrial ATP:ADP ratio but was not closely correlated with the extramitochondrial adenine nucleotide levels. When mitochondria were incubated in State 4 with succinate and rotenone, the addition of pyruvate increased PDHa activity more than 10-fold without appreciably altering the mitochondrial ATP:ADP ratio. These observations are most readily explained by the known inhibitory effects of pyruvate and ADP on PDHa kinase. PDHa activity could be maintained at a high level by incubating mitochondria in a condition resembling State 3 by the addition of succinate, glucose, and hexokinase. The further addition of octanoate reduced PDHa activity by 60% without appreciably altering the ATP:ADP ratio. Rotenone had a sililar effect. When added in the presence of octanoate, rotenone further decreased PDHa activity whereas 4-pentenoate led to an increase in activity. The effects of octanoate on PDHa activity were not seen when mitochondria were incubated in the presence of high levels of pyruvate, though pyruvate oxidation was till diminished by over 50%. The data suggest that octanoate addition favors the PDHa kinase reaction leading to inactivation of PDHa, and in addition causes the accumulation of NADH and acetyl-CoA which are recognized competitive inhibitors of pyruvate dehydrogenase. |
| | |
Authors:
|
S I Taylor; C Mukherjee; R L Jungas |
Related Documents
:
|
1633156 - Hydrolysis of phosphoenolpyruvate catalyzed by phosphoenolpyruvate carboxylase from zea... 15211516 - The molecular origin of the thiamine diphosphate-induced spectral bands of thdp-depende... 1319216 - Postnatal development of pyruvate oxidation in quadriceps muscle of the rat. 1983996 - Changes in pyruvate dehydrogenase complex activity during and following severe insulin-... 8951426 - Determination of manganese superoxide dismutase activity by direct spectrophotometry. 18068706 - Is dihydrolipoic acid among the reductive activators of parasite cyshis proteases? |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 250 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1975 Mar |
Date Detail:
|
Created Date: 1975-06-06 Completed Date: 1975-06-06 Revised Date: 2009-10-27 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 2028-35 Citation Subset: IM |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenosine Diphosphate
/
pharmacology* Adenosine Triphosphate / pharmacology* Adipose Tissue / enzymology Animals Caprylates / pharmacology* Centrifugation Dinitrophenols / pharmacology Freezing Glutamates / pharmacology Ketone Bodies / pharmacology Mitochondria, Liver / enzymology* Octanoic Acids / pharmacology* Oligomycins / pharmacology Organophosphorus Compounds / metabolism Oxidation-Reduction Pyruvate Dehydrogenase Complex / metabolism* Pyruvates / pharmacology Rats Rotenone / pharmacology |
| Chemical | |
Reg. No./Substance:
|
0/Caprylates; 0/Dinitrophenols; 0/Glutamates; 0/Ketone Bodies; 0/Octanoic Acids; 0/Oligomycins; 0/Organophosphorus Compounds; 0/Pyruvate Dehydrogenase Complex; 0/Pyruvates; 56-65-5/Adenosine Triphosphate; 58-64-0/Adenosine Diphosphate; 83-79-4/Rotenone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Capacity of the outer membrane of a gram-negative marine bacterium in the presence of cations to pre...
Next Document: Abnormal induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase in leukocytes from subjects wi...