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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1986-12-17
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pubmed:abstractText |
Adenosine 2'-monophospho-5'-diphosphoribose (P-ADP-Rib) is a structural analog of NADPH which was reported to competitively inhibit (Kiapp = 21.7 microM) solubilized rat liver 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (Tanazawa, K., and A. Endo. 1979. Eur. J. Biochem. 98: 195-201). However, microsomal HMG-CoA reductase, which at low thiol concentrations exhibits allosteric properties, is only poorly inhibited by P-ADP-Rib (Kiapp = 550 microM at 4.5 mM GSH). Gradual shift of the microsomal reductase towards a non-allosteric form by increasing glutathione (GSH) concentrations resulted in a higher inhibition by P-ADP-Rib. Under these conditions, Ki values for P-ADP-Rib were 165 microM and 53 microM at 9 mM and 27 mM GSH, respectively. The largest change in the degree of inhibition by P-ADP-Rib was observed within the 10 mM range of GSH. By contrast, freeze-thaw solubilized HMG-CoA reductase, which does not display allosteric properties, is readily inhibited by P-ADP-Rib, even when assayed at a low concentration of GSH (Kiapp = 50 microM at 4.5 mM GSH). Assaying the solubilized reductase in the presence of increased thiol concentration results in a minor decrease in the apparent Ki for P-ADP-Rib (22 microM at 27 mM GSH). Microsomal HMG-CoA reductase is allosterically activated by various nucleotides. When activated by NADH, the enzyme is effectively inhibited by P-ADP-Rib even at a 4.5-mM GSH concentration (Kiapp = 175 microM in the presence of 300 microM NADH).(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate Ribose,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl-CoA...,
http://linkedlifedata.com/resource/pubmed/chemical/NAD,
http://linkedlifedata.com/resource/pubmed/chemical/phosphoadenosine diphosphoribose
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-2275
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
828-35
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:3772249-Adenosine Diphosphate Ribose,
pubmed-meshheading:3772249-Allosteric Regulation,
pubmed-meshheading:3772249-Animals,
pubmed-meshheading:3772249-Female,
pubmed-meshheading:3772249-Glutathione,
pubmed-meshheading:3772249-Hydroxymethylglutaryl-CoA Reductase Inhibitors,
pubmed-meshheading:3772249-Kinetics,
pubmed-meshheading:3772249-Microsomes, Liver,
pubmed-meshheading:3772249-NAD,
pubmed-meshheading:3772249-Rats,
pubmed-meshheading:3772249-Rats, Inbred Strains
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pubmed:year |
1986
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pubmed:articleTitle |
Allosteric and non-allosteric forms of rat liver 3-hydroxy-3-methylglutaryl coenzyme A reductase: differential inhibition of activity by adenosine 2'-monophospho-5'-diphosphoribose.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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