Guanidinoacetate Is More Effective than Creatine at Enhancing Tissue Creatine Stores while Consequently Limiting Methionine Availability in Yucatan Miniature Pigs
Identifieur interne : 000076 ( Pmc/Curation ); précédent : 000075; suivant : 000077Guanidinoacetate Is More Effective than Creatine at Enhancing Tissue Creatine Stores while Consequently Limiting Methionine Availability in Yucatan Miniature Pigs
Auteurs : Laura E. Mcbreairty ; Jason L. Robinson ; Kayla R. Furlong ; Janet A. Brunton ; Robert F. BertoloSource :
- PLoS ONE [ 1932-6203 ] ; 2015.
Abstract
Creatine (Cr) is an important high-energy phosphate buffer in tissues with a high energy demand such as muscle and brain and is consequently a highly consumed nutritional supplement. Creatine is synthesized via the S-adenosylmethionine (SAM) dependent methylation of guanidinoacetate (GAA) which is not regulated by a feedback mechanism. The first objective of this study was to determine the effectiveness of GAA at increasing tissue Cr stores. Because SAM is required for other methylation reactions, we also wanted to determine whether an increased creatine synthesis would lead to a lower availability of methyl groups for other methylated products. Three month-old pigs (
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DOI: 10.1371/journal.pone.0131563
PubMed: 26110793
PubMed Central: 4482513
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Guanidinoacetate Is More Effective than Creatine at Enhancing Tissue Creatine Stores while Consequently Limiting Methionine Availability in Yucatan Miniature Pigs</title><author><name sortKey="Mcbreairty, Laura E" sort="Mcbreairty, Laura E" uniqKey="Mcbreairty L" first="Laura E." last="Mcbreairty">Laura E. Mcbreairty</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Robinson, Jason L" sort="Robinson, Jason L" uniqKey="Robinson J" first="Jason L." last="Robinson">Jason L. Robinson</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Furlong, Kayla R" sort="Furlong, Kayla R" uniqKey="Furlong K" first="Kayla R." last="Furlong">Kayla R. Furlong</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Brunton, Janet A" sort="Brunton, Janet A" uniqKey="Brunton J" first="Janet A." last="Brunton">Janet A. Brunton</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Bertolo, Robert F" sort="Bertolo, Robert F" uniqKey="Bertolo R" first="Robert F." last="Bertolo">Robert F. Bertolo</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26110793</idno><idno type="pmc">4482513</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482513</idno><idno type="RBID">PMC:4482513</idno><idno type="doi">10.1371/journal.pone.0131563</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000076</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000076</idno><idno type="wicri:Area/Pmc/Curation">000076</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000076</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Guanidinoacetate Is More Effective than Creatine at Enhancing Tissue Creatine Stores while Consequently Limiting Methionine Availability in Yucatan Miniature Pigs</title><author><name sortKey="Mcbreairty, Laura E" sort="Mcbreairty, Laura E" uniqKey="Mcbreairty L" first="Laura E." last="Mcbreairty">Laura E. Mcbreairty</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Robinson, Jason L" sort="Robinson, Jason L" uniqKey="Robinson J" first="Jason L." last="Robinson">Jason L. Robinson</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Furlong, Kayla R" sort="Furlong, Kayla R" uniqKey="Furlong K" first="Kayla R." last="Furlong">Kayla R. Furlong</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Brunton, Janet A" sort="Brunton, Janet A" uniqKey="Brunton J" first="Janet A." last="Brunton">Janet A. Brunton</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Bertolo, Robert F" sort="Bertolo, Robert F" uniqKey="Bertolo R" first="Robert F." last="Bertolo">Robert F. Bertolo</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Creatine (Cr) is an important high-energy phosphate buffer in tissues with a high energy demand such as muscle and brain and is consequently a highly consumed nutritional supplement. Creatine is synthesized via the S-adenosylmethionine (SAM) dependent methylation of guanidinoacetate (GAA) which is not regulated by a feedback mechanism. The first objective of this study was to determine the effectiveness of GAA at increasing tissue Cr stores. Because SAM is required for other methylation reactions, we also wanted to determine whether an increased creatine synthesis would lead to a lower availability of methyl groups for other methylated products. Three month-old pigs (<italic>n</italic> = 18) were fed control, GAA- or Cr-supplemented diets twice daily. On day 18 or 19, anesthesia was induced 1–3 hours post feeding and a bolus of [methyl-<sup>3</sup>H]methionine was intravenously infused. After 30 minutes, the liver was analyzed for methyl-<sup>3</sup>H incorporation into protein, Cr, phosphatidylcholine (PC) and DNA. Although both Cr and GAA led to higher hepatic Cr concentration, only supplementation with GAA led to higher levels of muscle Cr (<italic>P</italic> < 0.05). Only GAA supplementation resulted in lower methyl-<sup>3</sup>H incorporation into PC and protein as well as lower hepatic SAM concentration compared to the controls, suggesting that Cr synthesis resulted in a limited methyl supply for PC and protein synthesis (<italic>P</italic> < 0.05). Although GAA is more effective than Cr at supporting muscle Cr accretion, further research should be conducted into the long term consequences of a limited methyl supply and its effects on protein and PC homeostasis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Stead, Lm" uniqKey="Stead L">LM Stead</name></author><author><name sortKey="Brosnan, Jt" uniqKey="Brosnan J">JT Brosnan</name></author><author><name sortKey="Brosnan, Me" uniqKey="Brosnan M">ME Brosnan</name></author><author><name sortKey="Vance, De" uniqKey="Vance D">DE Vance</name></author><author><name sortKey="Jacobs, Rl" uniqKey="Jacobs R">RL Jacobs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wyss, M" uniqKey="Wyss M">M Wyss</name></author><author><name sortKey="Kaddurah Daouk, R" uniqKey="Kaddurah Daouk R">R Kaddurah-Daouk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walker, Jb" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26110793</article-id><article-id pub-id-type="pmc">4482513</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0131563</article-id><article-id pub-id-type="publisher-id">PONE-D-15-04154</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Guanidinoacetate Is More Effective than Creatine at Enhancing Tissue Creatine Stores while Consequently Limiting Methionine Availability in Yucatan Miniature Pigs</article-title><alt-title alt-title-type="running-head">Guanidinoacetate and Creatine Accretion</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>McBreairty</surname><given-names>Laura E.</given-names></name><xref ref-type="aff" rid="aff001"></xref></contrib><contrib contrib-type="author"><name><surname>Robinson</surname><given-names>Jason L.</given-names></name><xref ref-type="aff" rid="aff001"></xref></contrib><contrib contrib-type="author"><name><surname>Furlong</surname><given-names>Kayla R.</given-names></name><xref ref-type="aff" rid="aff001"></xref></contrib><contrib contrib-type="author"><name><surname>Brunton</surname><given-names>Janet A.</given-names></name><xref ref-type="aff" rid="aff001"></xref></contrib><contrib contrib-type="author"><name><surname>Bertolo</surname><given-names>Robert F.</given-names></name><xref rid="cor001" ref-type="corresp">*</xref><xref ref-type="aff" rid="aff001"></xref></contrib></contrib-group><aff id="aff001"><addr-line>Department of Biochemistry, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Dzeja</surname><given-names>Petras</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Mayo Clinic, UNITED STATES</addr-line></aff><author-notes><fn fn-type="conflict" id="coi001"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: LEM JLR RFB JAB. Performed the experiments: LEM JLR KRF. Analyzed the data: LEM KRF JLR RFB JAB. Contributed reagents/materials/analysis tools: RFB JAB. Wrote the paper: LEM RFB.</p></fn><corresp id="cor001">* E-mail: <email>rbertolo@mun.ca</email></corresp></author-notes><pub-date pub-type="epub"><day>25</day><month>6</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2015</year></pub-date><volume>10</volume><issue>6</issue><elocation-id>e0131563</elocation-id><history><date date-type="received"><day>28</day><month>1</month><year>2015</year></date><date date-type="accepted"><day>3</day><month>6</month><year>2015</year></date></history><permissions><copyright-year>2015</copyright-year><copyright-holder>McBreairty et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="pone.0131563.pdf"></self-uri><abstract><p>Creatine (Cr) is an important high-energy phosphate buffer in tissues with a high energy demand such as muscle and brain and is consequently a highly consumed nutritional supplement. Creatine is synthesized via the S-adenosylmethionine (SAM) dependent methylation of guanidinoacetate (GAA) which is not regulated by a feedback mechanism. The first objective of this study was to determine the effectiveness of GAA at increasing tissue Cr stores. Because SAM is required for other methylation reactions, we also wanted to determine whether an increased creatine synthesis would lead to a lower availability of methyl groups for other methylated products. Three month-old pigs (<italic>n</italic> = 18) were fed control, GAA- or Cr-supplemented diets twice daily. On day 18 or 19, anesthesia was induced 1–3 hours post feeding and a bolus of [methyl-<sup>3</sup>H]methionine was intravenously infused. After 30 minutes, the liver was analyzed for methyl-<sup>3</sup>H incorporation into protein, Cr, phosphatidylcholine (PC) and DNA. Although both Cr and GAA led to higher hepatic Cr concentration, only supplementation with GAA led to higher levels of muscle Cr (<italic>P</italic> < 0.05). Only GAA supplementation resulted in lower methyl-<sup>3</sup>H incorporation into PC and protein as well as lower hepatic SAM concentration compared to the controls, suggesting that Cr synthesis resulted in a limited methyl supply for PC and protein synthesis (<italic>P</italic> < 0.05). Although GAA is more effective than Cr at supporting muscle Cr accretion, further research should be conducted into the long term consequences of a limited methyl supply and its effects on protein and PC homeostasis.</p></abstract><funding-group><funding-statement>This research was funded by a Janeway Children's Hospital Foundation research grant awarded to RFB LEM JLR. Funding was also provided by The Research and Development Corporation of Newfoundland and Labrador (<ext-link ext-link-type="uri" xlink:href="http://RDC.org">RDC.org</ext-link>) and the Canadian Institute of Health Research (<ext-link ext-link-type="uri" xlink:href="http://www.cihr-irsc.gc.ca/e/193.html">http://www.cihr-irsc.gc.ca/e/193.html</ext-link>); grant number 201103RNL awarded to RFB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="0"></fig-count><table-count count="5"></table-count><page-count count="11"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the paper.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the paper.</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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