RESUMEN
Previous studies in our laboratory showed that isolated, intact adult rat liver mitochondria are able to oxidize the 3-carbon of serine and the N-methyl carbon of sarcosine to formate without the addition of any other cofactors or substrates. Conversion of these 1-carbon units to formate requires several folate-interconverting enzymes in mitochondria. The enzyme(s) responsible for conversion of 5,10-methylene-tetrahydrofolate (CH(2)-THF) to 10-formyl-THF in adult mammalian mitochondria are currently unknown. A new mitochondrial CH(2)-THF dehydrogenase isozyme, encoded by the MTHFD2L gene, has now been identified. The recombinant protein exhibits robust NADP(+)-dependent CH(2)-THF dehydrogenase activity when expressed in yeast. The enzyme is localized to mitochondria when expressed in CHO cells and behaves as a peripheral membrane protein, tightly associated with the matrix side of the mitochondrial inner membrane. The MTHFD2L gene is subject to alternative splicing and is expressed in adult tissues in humans and rodents. This CH(2)-THF dehydrogenase isozyme thus fills the remaining gap in the pathway from CH(2)-THF to formate in adult mammalian mitochondria.
Asunto(s)
Regulación Enzimológica de la Expresión Génica/fisiología , Metilenotetrahidrofolato Deshidrogenasa (NADP)/biosíntesis , Mitocondrias/enzimología , Proteínas Mitocondriales/biosíntesis , Empalme Alternativo/fisiología , Animales , Células CHO , Cricetinae , Cricetulus , Humanos , Isoenzimas/biosíntesis , Isoenzimas/genética , Metilenotetrahidrofolato Deshidrogenasa (NADP)/genética , Mitocondrias/genética , Proteínas Mitocondriales/genética , Especificidad de Órganos/fisiología , Ratas , Ratas Sprague-Dawley , Tetrahidrofolatos/metabolismoRESUMEN
The predominant mode of strontium ion transfer from aqueous nitrate media into a series of 1-fluoroalkyl-3-methylimidazolium bis[(trifluoromethylsulfonyl)]imides containing dicyclohexano-18-crown-6 (DCH18C6) is shown to shift from cation exchange to strontium nitrato-crown ether complex partitioning as the length of the fluoroalkyl substituent is increased. Fluoroalkyl substituents are shown to be only slightly more effective than their non-fluorous analogs at inducing this shift. At the same time, the fluorinated ionic liquids (ILs) yield strontium distribution ratios as much as an order of magnitude lower than the corresponding 1-alkyl-3-methylimidazolium (C(n)mim(+)) salts. Fluorous ILs thus appear to offer no compelling advantages over C(n)mim(+) ionic liquids as extraction solvents.