| pubmed-article:19469483 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19469483 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:19469483 | lifeskim:mentions | umls-concept:C0005821 | lld:lifeskim |
| pubmed-article:19469483 | lifeskim:mentions | umls-concept:C0035286 | lld:lifeskim |
| pubmed-article:19469483 | lifeskim:mentions | umls-concept:C0003691 | lld:lifeskim |
| pubmed-article:19469483 | lifeskim:mentions | umls-concept:C0003695 | lld:lifeskim |
| pubmed-article:19469483 | lifeskim:mentions | umls-concept:C1261322 | lld:lifeskim |
| pubmed-article:19469483 | lifeskim:mentions | umls-concept:C0598002 | lld:lifeskim |
| pubmed-article:19469483 | pubmed:issue | 26 | lld:pubmed |
| pubmed-article:19469483 | pubmed:dateCreated | 2009-6-30 | lld:pubmed |
| pubmed-article:19469483 | pubmed:abstractText | Human reticulocyte 15-lipoxygenase-1 (15-hLO-1) and human platelet 12-lipoxygenase (12-hLO) have been implicated in a number of diseases, with differences in their relative activity potentially playing a central role. In this work, we characterize the catalytic mechanism of these two enzymes with arachidonic acid (AA) as the substrate. Using variable-temperature kinetic isotope effects (KIE) and solvent isotope effects (SIE), we demonstrate that both k(cat)/K(M) and k(cat) for 15-hLO-1 and 12-hLO involve multiple rate-limiting steps that include a solvent-dependent step and hydrogen atom abstraction. A relatively low k(cat)/K(M) KIE of 8 was determined for 15-hLO-1, which increases to 18 upon the addition of the allosteric effector molecule, 12-hydroxyeicosatetraenoic acid (12-HETE), indicating a tunneling mechanism. Furthermore, the addition of 12-HETE lowers the observed k(cat)/K(M) SIE from 2.2 to 1.4, indicating that the rate-limiting contribution from a solvent sensitive step in the reaction mechanism of 15-hLO-1 has decreased, with a concomitant increase in the C-H bond abstraction contribution. Finally, the allosteric binding of 12-HETE to 15-hLO-1 decreases the K(M)[O(2)] for AA to 15 microM but increases the K(M)[O(2)] for linoleic acid (LA) to 22 microM, such that the k(cat)/K(M)[O(2)] values become similar for both substrates (approximately 0.3 s(-1) microM(-1)). Considering that the oxygen concentration in cancerous tissue can be less than 5 microM, this result may have cellular implications with respect to the substrate specificity of 15-hLO-1. | lld:pubmed |
| pubmed-article:19469483 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19469483 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19469483 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19469483 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:19469483 | pubmed:issn | 1520-4995 | lld:pubmed |
| pubmed-article:19469483 | pubmed:author | pubmed-author:van der... | lld:pubmed |
| pubmed-article:19469483 | pubmed:author | pubmed-author:HolmanTheodor... | lld:pubmed |
| pubmed-article:19469483 | pubmed:author | pubmed-author:WeckslerAaron... | lld:pubmed |
| pubmed-article:19469483 | pubmed:author | pubmed-author:JacquotCyrilC | lld:pubmed |
| pubmed-article:19469483 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19469483 | pubmed:day | 7 | lld:pubmed |
| pubmed-article:19469483 | pubmed:volume | 48 | lld:pubmed |
| pubmed-article:19469483 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19469483 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19469483 | pubmed:pagination | 6259-67 | lld:pubmed |
| pubmed-article:19469483 | pubmed:dateRevised | 2011-9-26 | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:meshHeading | pubmed-meshheading:19469483... | lld:pubmed |
| pubmed-article:19469483 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19469483 | pubmed:articleTitle | Mechanistic investigations of human reticulocyte 15- and platelet 12-lipoxygenases with arachidonic acid. | lld:pubmed |
| pubmed-article:19469483 | pubmed:affiliation | Chemistry and Biochemistry Department, University of California, Santa Cruz, California 95064, USA. | lld:pubmed |
| pubmed-article:19469483 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:19469483 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:19469483 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| entrez-gene:239 | entrezgene:pubmed | pubmed-article:19469483 | lld:entrezgene |
| entrez-gene:246 | entrezgene:pubmed | pubmed-article:19469483 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:19469483 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:19469483 | lld:entrezgene |
