Linked Life Data

238978

Source:http://linkedlifedata.com/resource/pubmed/id/238978

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1975-11-6
pubmed:abstractText
Fatty acid synthetase complex (Mr = 500,000) purified from pigeon liver homogenates is inactivated by phenylmethylsulfonyl fluoride. A well characterized inhibitor of serine esterases. Pseudounimolecular kinetics are followed at all inhibitor concentrations studied (0.05 to 1.0 mM). The second order rate constant obtained at pH 7.0, 30 degrees in 0.05 M potassium phosphate, 1 mM EDTA is 250 plus or minus 10 M-1 min-1 and appears to be independent of pH between 6 and 7.9. The inactivation of the enzyme complex appears to be selective since only one of the several component enzymes of fatty acid synthesis, palmityl-CoA deacylase, is inhibited. Acetyl- and malonyl-CoA-pantetheine transacylase activities as well as the kinetics of the reduction and dehydration steps are nearly identical for the native and the modified enzymes. The rate of approach of the condensation-CO2 exchange reaction (substrates: hexanoyl-CoA, malonyl-CoA, CoA, and H14CO3-) is slightly slower in the modified enzyme, though this change is not large enough to account for total loss of activity for fatty acid synthesis. The rate of loss of palmityl-CoA deacylase activity at a constant inhibitor concentration follows biphasic kinetics. Complete inactivation is achieved only after 2 mol of the inhibitor are bound per mol of the enzyme complex. Acetyl-, butyryl-, and hexanoyl-CoA thioesters (at 1.0 mM concentrations) protect the enzyme complex against inactivation by phenylmethylsulfonyl fluoride whereas CoA has no effect. Malonyl-CoA on the other hand, promotes inhibitor-mediated inactivation. Of the N-acetyl cysteamine derivatives tested, S-acetyl-N-acetyl cysteamine (at 10 mM) gives almost complete protection against inactivation whereas S-acetoacetyl-, S-beta-hydroxybutyryl-, and S-crotonyl-N-acetyl cysteamine thioesters exhibit either slight or no protection. These data demonstrate that phenylmethylsulfonyl fluoride is a selective reagent for the inactivation of functional fatty acyl deacylase component(s) of the pigeon liver fatty acid synthetase complex, and that it has no effect on malonyl or acetyl transacylases. The data are also in accord with the postulation that the inhibitor interacts at two catalytic centers of the enzyme complex. Furthermore, the patterns of protective effects shown by saturated acyl-CoA asters and malonyl-CoA point to different mechanisms of deacylation for these esters.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Acetyl Coenzyme A, http://linkedlifedata.com/resource/pubmed/chemical/Acyltransferases, http://linkedlifedata.com/resource/pubmed/chemical/Carbon Dioxide, http://linkedlifedata.com/resource/pubmed/chemical/Carbon Radioisotopes, http://linkedlifedata.com/resource/pubmed/chemical/Coenzyme A, http://linkedlifedata.com/resource/pubmed/chemical/Cysteamine, http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acid Synthetase Complex, http://linkedlifedata.com/resource/pubmed/chemical/Malonates, http://linkedlifedata.com/resource/pubmed/chemical/Palmitic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Pantetheine, http://linkedlifedata.com/resource/pubmed/chemical/Phenylmethylsulfonyl Fluoride, http://linkedlifedata.com/resource/pubmed/chemical/Sulfones
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
250
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5150-8
pubmed:dateRevised
2009-10-27
pubmed:meshHeading
pubmed:year
1975
pubmed:articleTitle
Functional deacylases of pigeon liver fatty acid synthetase complex.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.