pubmed-article:7702568 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:7702568 | lifeskim:mentions | umls-concept:C0567416 | lld:lifeskim |
pubmed-article:7702568 | lifeskim:mentions | umls-concept:C0205107 | lld:lifeskim |
pubmed-article:7702568 | lifeskim:mentions | umls-concept:C0025519 | lld:lifeskim |
pubmed-article:7702568 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
pubmed-article:7702568 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
pubmed-article:7702568 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
pubmed-article:7702568 | lifeskim:mentions | umls-concept:C0012120 | lld:lifeskim |
pubmed-article:7702568 | lifeskim:mentions | umls-concept:C0044085 | lld:lifeskim |
pubmed-article:7702568 | lifeskim:mentions | umls-concept:C0562700 | lld:lifeskim |
pubmed-article:7702568 | pubmed:dateCreated | 1995-4-28 | lld:pubmed |
pubmed-article:7702568 | pubmed:abstractText | Stalk cell differentiation during development of the slime mould Dictyostelium is induced by a chlorinated alkyl phenone called differentiation-inducing factor-1 (DIF-1). Inactivation of DIF-1 is likely to be a key element in the DIF-1 signalling system, and we have shown previously that this is accomplished by a dedicated metabolic pathway involving up to 12 unidentified metabolites. We report here the structure of the first four metabolites produced from DIF-1, as deduced by m.s., n.m.r. and chemical synthesis. The structures of these compounds show that the first step in metabolism is a dechlorination of the phenolic ring, producing DIF metabolite 1 (DM1). DM1 is identical with the previously known minor DIF activity, DIF-3. DIF-3 is then metabolized by three successive oxidations of its aliphatic side chain: a hydroxylation at omega-2 to produce DM2, oxidation of the hydroxy group to a ketone group to produce DM3 and a further hydroxylation at omega-1 to produce DM4, a hydroxyketone of DIF-3. We have investigated the enzymology of DIF-1 metabolism. It is already known that the first step, to produce DIF-3, is catalysed by a novel dechlorinase. The enzyme activity responsible for the first side-chain oxidation (DIF-3 hydroxylase) was detected by incubating [3H]DIF-3 with cell-free extracts and resolving the reaction products by t.l.c. DIF-3 hydroxylase has many of the properties of a cytochrome P-450. It is membrane-bound and uses NADPH as co-substrate. It is also inhibited by CO, the classic cytochrome P-450 inhibitor, and by several other cytochrome P-450 inhibitors, as well as by diphenyliodonium chloride, an inhibitor of cytochrome P-450 reductase. DIF-3 hydroxylase is highly specific for DIF-3: other closely related compounds do not compete for the activity at 100-fold molar excess, with the exception of the DIF-3 analogue lacking the chlorine atom. The Km for DIF-3 of 47 nM is consistent with this enzyme being responsible for DIF-3 metabolism in vivo. The two further oxidations necessary to produce DM4 are also performed in vitro by similar enzyme activities. One of the inhibitors of DIF-3 hydroxylase, ancymidol (IC50 67 nM) is likely to be particularly suitable for probing the function of DIF metabolism during development. | lld:pubmed |
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pubmed-article:7702568 | pubmed:language | eng | lld:pubmed |
pubmed-article:7702568 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:7702568 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:7702568 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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pubmed-article:7702568 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:7702568 | pubmed:month | Mar | lld:pubmed |
pubmed-article:7702568 | pubmed:issn | 0264-6021 | lld:pubmed |
pubmed-article:7702568 | pubmed:author | pubmed-author:LINS CSC | lld:pubmed |
pubmed-article:7702568 | pubmed:author | pubmed-author:TaylorG WGW | lld:pubmed |
pubmed-article:7702568 | pubmed:author | pubmed-author:NaylerOO | lld:pubmed |
pubmed-article:7702568 | pubmed:author | pubmed-author:TraynorDD | lld:pubmed |
pubmed-article:7702568 | pubmed:author | pubmed-author:NeuhausDD | lld:pubmed |
pubmed-article:7702568 | pubmed:author | pubmed-author:MorandiniPP | lld:pubmed |
pubmed-article:7702568 | pubmed:author | pubmed-author:OfferJJ | lld:pubmed |
pubmed-article:7702568 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:7702568 | pubmed:day | 15 | lld:pubmed |
pubmed-article:7702568 | pubmed:volume | 306 ( Pt 3) | lld:pubmed |
pubmed-article:7702568 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:7702568 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:7702568 | pubmed:pagination | 735-43 | lld:pubmed |
pubmed-article:7702568 | pubmed:dateRevised | 2010-9-13 | lld:pubmed |
pubmed-article:7702568 | pubmed:meshHeading | pubmed-meshheading:7702568-... | lld:pubmed |
pubmed-article:7702568 | pubmed:meshHeading | pubmed-meshheading:7702568-... | lld:pubmed |
pubmed-article:7702568 | pubmed:meshHeading | pubmed-meshheading:7702568-... | lld:pubmed |
pubmed-article:7702568 | pubmed:meshHeading | pubmed-meshheading:7702568-... | lld:pubmed |
pubmed-article:7702568 | pubmed:meshHeading | pubmed-meshheading:7702568-... | lld:pubmed |
pubmed-article:7702568 | pubmed:meshHeading | pubmed-meshheading:7702568-... | lld:pubmed |
pubmed-article:7702568 | pubmed:year | 1995 | lld:pubmed |
pubmed-article:7702568 | pubmed:articleTitle | The proximal pathway of metabolism of the chlorinated signal molecule differentiation-inducing factor-1 (DIF-1) in the cellular slime mould Dictyostelium. | lld:pubmed |
pubmed-article:7702568 | pubmed:affiliation | MRC Laboratory of Molecular Biology, Cambridge, U.K. | lld:pubmed |
pubmed-article:7702568 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:7702568 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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