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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4 Pt 1
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pubmed:dateCreated |
1991-11-18
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pubmed:abstractText |
Measurement of hepatic fatty acid (FA) and cholesterol synthesis has been limited by lack of access to the precursor pool, cytosolic acetyl-CoA. We present a method for inferring the enrichment of the true hepatic lipogenic precursor pool in humans using the frequency distribution of mass isotopomers within enriched circulating polymers of acetyl-CoA [very low-density lipoprotein (VLDL)-palmitate, VLDL-stearate]. Human subjects were infused intravenously (n = 16) with [1-13C]- or [2-13C]acetate. Oral sulfamethoxazole (SMX) was administered concurrently, and the acetylated conjugate (SMX acetate) was used to estimate independently the hepatic cytosolic acetyl-CoA enrichment. Isotopomer frequencies in VLDL-FA were determined by gas chromatography-mass spectrometry, whereas high-performance liquid chromatography-mass spectrometry was used to measure enrichments in SMX acetate. Based on the excess M2/excess M1 ratio in VLDL-FA, calculated acetyl-CoA enrichments were 5.59 +/- 0.33 molar percent excess (MPE), whereas SMX acetate enrichments were 5.38 +/- 0.31 MPE (the 2 methods were not significantly different). Mass isotopomer-calculated and SMX acetate-measured estimates of acetyl-CoA enrichments correlated very closely in individual subjects (r2 = 0.93; P less than 0.0001). De novo hepatic lipogenesis can be measured using isotopomer-calculated precursor enrichments compared with measured incorporation in specific isotopomers of VLDL-FA. In summary, excess isotopomer frequencies in secreted lipids provide a non-invasive technique for estimating hepatic cytosolic acetyl-CoA enrichments in humans in vivo and correlate closely with enrichments observed using the xenobiotic probe technique. Isotopomeric distributions represent a new strategy for accurate measurement of macromolecule synthesis that may be applicable to other classes of molecules besides lipids.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetates,
http://linkedlifedata.com/resource/pubmed/chemical/Acetyl Coenzyme A,
http://linkedlifedata.com/resource/pubmed/chemical/Carbon Isotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, VLDL,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfamethoxazole,
http://linkedlifedata.com/resource/pubmed/chemical/Xenobiotics
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0002-9513
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
261
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
E479-86
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1928339-Acetates,
pubmed-meshheading:1928339-Acetyl Coenzyme A,
pubmed-meshheading:1928339-Carbon Isotopes,
pubmed-meshheading:1928339-Chromatography, High Pressure Liquid,
pubmed-meshheading:1928339-Cytosol,
pubmed-meshheading:1928339-Fatty Acids,
pubmed-meshheading:1928339-Humans,
pubmed-meshheading:1928339-Lipids,
pubmed-meshheading:1928339-Lipoproteins, VLDL,
pubmed-meshheading:1928339-Liver,
pubmed-meshheading:1928339-Models, Biological,
pubmed-meshheading:1928339-Sulfamethoxazole,
pubmed-meshheading:1928339-Xenobiotics
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pubmed:year |
1991
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pubmed:articleTitle |
Use of mass isotopomer distributions in secreted lipids to sample lipogenic acetyl-CoA pool in vivo in humans.
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pubmed:affiliation |
Department of Nutritional Sciences, University of California, Berkeley 94720.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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