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Different Metabolic Pathways (different + metabolic_pathway)
Selected AbstractsInterstrand crosslink inducing agents in pretransplant conditioning therapy for hematologic malignanciesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2010Benigno C. Valdez Abstract Despite successful molecularly targeted, highly specific, therapies for hematologic malignancies, the DNA interstrand crosslinking agents, which are among the oldest and least specific cytotoxic drugs, still have an important role. This is particularly true in stem cell transplantation, where virtually every patient receives conditioning therapy with a DNA-alkylating agent-based program. However, due to concern about serious additive toxicities with combinations of different alkylating drugs, the last several years have seen nucleoside analogs, whose cytotoxic action follows vastly different molecular pathways, introduced in combination with alkylating agents. The mechanistic differences paired with different metabolic pathways for the respective drugs have clinically translated into increased safety without appreciable loss of antileukemic activity. In this report, we review pre-clinical evidence for synergistic antileukemic activity when nucleoside analog(s) and DNA-alkylating agent(s) are combined in the most appropriate manner(s), without a measurable decrease in clinical efficacy compared with the more established alkylating agent combinations. Data from our own laboratory using combinations of fludarabine, clofarabine, and busulfan as prototype representatives for these respective classes of cytotoxic agents are combined with information from other investigators to explain how the observed molecular events will result in greatly enhanced synergistic cytotoxicity. We further present possible mechanistic pathways for such desirable cytotoxic synergism. Finally, we propose how this information-backed hypothesis can be incorporated in the design of the next generation conditioning therapy programs in stem cell transplantation to optimize antileukemic efficacy while still safeguarding patient safety. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc. [source] Impact of selected inborn errors of metabolism on prenatal and neonatal developmentIUBMB LIFE, Issue 6 2010Sabine Illsinger Abstract In general, data regarding maturational processes of different metabolic pathways in the very vulnerable fetal and neonatal period are rare. This review is to substantiate the impact of selected inborn errors of metabolism on this critical period of life and their clinical manifestation. Significant adaptation of mitochondrial/energy-, carbohydrate-, lysosomal-, and amino acid-metabolism occurs during early prenatal and neonatal development. In utero, metabolic environment has an impact on the development of the fetus as well as fetal organ maturation. Defects of distinct metabolic pathways could therefore already be of significant relevance in utero and for clinical manifestations in the early fetal and neonatal period. Disturbances of these pathways may influence intrauterine growth and health. Production of a toxic intrauterine milieu, energy-deficiency, modification of membrane function, or disturbance of the normal intrauterine expression of genes may be responsible for fetal compromise and developmental disorders. Three categories of metabolic disorders will be discussed: the "intoxication type" (classical galactosemia, ornithine transcarbamylase deficiency, and "maternal phenylketonuria"), the "storage type" (Morbus Niemann Pick type C), and the "energy deficient type" (including long-chain fatty acid oxidation disorders, pyruvate dehydrogenase deficiency, and respiratory chain defects). For these disorders, the pathophysiology of early manifestation, special aspects regarding the prenatal and neonatal period, and diagnostic as well as therapeutic options are presented. © 2010 IUBMB IUBMB Life, 62(6): 403,413, 2010 [source] A novel finding that Streptomyces clavuligerus can produce the antibiotic clavulanic acid using olive oil as a sole carbon sourceJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2008G. Efthimiou Abstract Aims:, This study aims to establish whether commercially available food oils can be used by Streptomyces clavuligerus as sole carbon sources for growth and clavulanic acid production. Methods and results:, Batch cultures in bioreactors showed that Strep. clavuligerus growth and clavulanic acid yields in a P-limited medium containing 0.6% (v/v) olive oil were respectively 2.5- and 2.6-fold higher than in a glycerol-containing medium used as control. Glycerol- and olive oil-grown cells present different macromolecular composition, particularly lipid and protein content. Conclusions:,Streptomyces clavuligerus uses olive oil as the sole carbon and energy source for growth and clavulanic acid production. Yields and production rates in olive oil are comparable to those reported for oil-containing complex media. Differences in yields and in the macromolecular composition indicate that different metabolic pathways convert substrate into product. Significance and impact of the study:, This is the first report of oils being used as the sole carbon source by Strep. clavuligerus. Apart from economic benefits, interesting questions are raised about Strep. clavuligerus physiology. Defined culture media allow physiological studies to be performed in the absence of interference by other compounds. Understanding how Strep. clavuligerus catabolises oils may have an economic impact in clavulanic acid production. [source] The thioredoxin system,From science to clinicMEDICINAL RESEARCH REVIEWS, Issue 1 2004Stephan Gromer Abstract The thioredoxin system,formed by thioredoxin reductase and its characteristic substrate thioredoxin,is an important constituent of the intracellular redox milieu. Interactions with many different metabolic pathways such as DNA-synthesis, selenium metabolism, and the antioxidative network as well as significant species differences render this system an attractive target for chemotherapeutic approaches in many fields of medicine,ranging from infectious diseases to cancer therapy. In this review we will present and evaluate the preclinical and clinical results available today. Current trends in drug development are emphasized. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 1, 40,89, 2004 [source] Molecular analysis of resistance mechanisms to Orobanche cumana in sunflowerPLANT PATHOLOGY, Issue 3 2007P. Letousey Resistance to the dicotyledenous parasite Orobanche cumana in sunflower is characterized by a low number of parasitic attachments and a confinement of the parasite in host tissues leading to its necrosis. To help understand what determines such resistance mechanisms, molecular, biochemical and histological approaches were employed before (early response) and after (late response) attachment of the broomrape parasite to susceptible (2603) and resistant (LR1) sunflower genotypes. The expression patterns of 11 defence-related genes known to be involved in different metabolic pathways (phenylpropanoids, jasmonate, ethylene) and/or in resistance mechanisms against microorganisms were investigated. RT-PCR and cDNA blot experiments revealed that the resistant genotype exhibited a stronger overall defence response against O. cumana than the susceptible one, involving marker genes of the jasmonate (JA) and salicylic acid (SA) pathways. Among them, the SA-responsive gene, def. (defensin), appeared to be characteristic of LR1 sunflower resistance. However, no JA accumulation and similar SA contents (250,300 ng g,1 FW) were measured by GC/MS in both genotypes, parasitized or not. In addition, three cDNAs, isolated by a suppression-subtractive hybridization, were shown to be strongly induced only in the resistant genotype 8 days post-inoculation, when the first O. cumana attachments occurred. These genes, putatively encoding a methionine synthase, a glutathione S-transferase and a quinone oxidoreductase, might be involved in detoxification of reactive oxygen species, suggesting the occurrence of an oxidative burst during the incompatible interaction. Finally, host cell-wall modifications leading to parasite-confinement were correlated with more intense callose depositions in the resistant genotype, concomitant with over-expression of the callose synthase cDNA HaGSL1. [source] Proteomic analysis of liver tissues subjected to early ischemia/reperfusion injury during human orthotopic liver transplantationPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2006Carlo Vascotto Abstract Knowledge of early molecular events occurring upon ischemia/reperfusion,(I/R) during liver transplantation,(LT) is of great importance to improve the therapeutic intervention of surgical treatment. However, nowadays, few data are available on early protein targets of I/R,injury. To identify these proteins, we used a differential proteomics approach in the characterization human liver biopsies during I/R upon,LT. Analyses were performed on nine donor livers during LT. By using 2-DE and MALDI-TOF,MS, we identified 36,proteins which resulted significantly altered upon I/R,injury. The majority of these proteins are functionally involved in lipid and energy metabolism, in different metabolic pathways, in redox signalling and in oxidative-stress response. Our data represent the first global approach in the study of I/R,injury in liver. [source] Conjugated linoleic acid isomers: Differences in metabolism and biological effectsBIOFACTORS, Issue 1 2009Itziar Churruca Abstract The term conjugated linoleic acid (CLA) refers to a mixture of linoleic acid positional and geometric isomers, characterized by having conjugated double bonds, not separated by a methylene group as in linoleic acid. CLA isomers appear as a minor component of the lipid fraction, found mainly in meat and dairy products from cows and sheep. The most abundant isomer is cis -9,trans -11, which represents up to 80% of total CLA in food. These isomers are metabolized in the body through different metabolic pathways, but important differences, that can have physiological consequences, are observed between the two main isomers. The trans -10,cis -12 isomer is more efficiently oxidized than the cis -9,trans -11 isomer, due to the position of its double bounds. Interest in CLA arose in its anticarcinogenic action but there is an increasing amount of specific scientific literature concerning the biological effects and properties of CLA. Numerous biological effects of CLA are due to the separate action of the most studied isomers, cis -9,trans -11 and trans -10,cis -12. It is also likely that some effects are induced and/or enhanced by these isomers acting synergistically. Although the cis -9,trans -11 isomer is mainly responsible for the anticarcinogenic effect, the trans -10,cis -12 isomer reduces body fat and it is referred as the most effective isomer affecting blood lipids. As far as insulin function is concerned, both isomers seem to be responsible for insulin resistance in humans. Finally, with regard to the immune system it is not clear whether individual isomers of CLA could act similarly or differently. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source] | |||||||||||||