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Degradative Pathway (degradative + pathway)
Selected AbstractsAutophagic pathways and metabolic stressDIABETES OBESITY & METABOLISM, Issue 2010S. Kaushik Autophagy is an essential intracellular process that mediates degradation of intracellular proteins and organelles in lysosomes. Autophagy was initially identified for its role as alternative source of energy when nutrients are scarce but, in recent years, a previously unknown role for this degradative pathway in the cellular response to stress has gained considerable attention. In this review, we focus on the novel findings linking autophagic function with metabolic stress resulting either from proteins or lipids. Proper autophagic activity is required in the cellular defense against proteotoxicity arising in the cytosol and also in the endoplasmic reticulum, where a vast amount of proteins are synthesized and folded. In addition, autophagy contributes to mobilization of intracellular lipid stores and may be central to lipid metabolism in certain cellular conditions. In this review, we focus on the interrelation between autophagy and different types of metabolic stress, specifically the stress resulting from the presence of misbehaving proteins within the cytosol or in the endoplasmic reticulum and the stress following a lipogenic challenge. We also comment on the consequences that chronic exposure to these metabolic stressors could have on autophagic function and on how this effect may underlie the basis of some common metabolic disorders. [source] Evolution of a chlorobenzene degradative pathway among bacteria in a contaminated groundwater mediated by a genomic island in RalstoniaENVIRONMENTAL MICROBIOLOGY, Issue 3 2003Tina Andrea Müller Summary The genetic structure of two Ralstonia spp., strain JS705 and strain JS745, isolated from the same groundwater aquifer, was characterized with respect to the degradation capacities for toluene and chlorobenzene degradation. Cosmid library construction, cloning, DNA sequencing and mating experiments indicated that the genes for chlorobenzene degradation in strain JS705 were a mosaic of the clc genes, previously described for Pseudomonas sp. strain B13, and a 5 kb fragment identical to strain JS745. The 5 kb fragment identical to both JS705 and JS745 was flanked in JS705 by one complete and one incomplete insertion (IS) element. This suggested involvement of the IS element in mobilizing the genes from JS745 to JS705, although insertional activity of the IS element in its present configuration could not be demonstrated. The complete genetic structure for chlorobenzene degradation in strain JS705 resided on a genomic island very similar to the clc element (Ravatn, R., Studer, S., Springael, D., Zehnder, A.J., van der Meer, J.R. 1998. Chromosomal integration, tandem amplification, and deamplification in Pseudomonas putida F1 of a 105-kilobase genetic element containing the chlorocatechol degradative genes from Pseudomonas sp. strain B13. J Bacteriol 180: 4360,4369). The unique reconstruction of formation of a metabolic pathway through the activity of IS elements and a genomic island in the chlorobenzene-degrading strain JS705 demonstrated how pathway evolution can occur under natural conditions in a few ,steps'. [source] Isolation and characterization of a bacterial strain of the genus Ochrobactrum with methyl parathion mineralizing activityJOURNAL OF APPLIED MICROBIOLOGY, Issue 5 2006X.-H. Qiu Abstract Aims:, To isolate and characterize a methyl parathion (MP)-mineralizing bacterium, and to elucidate the degradative pathway of MP and localize the responsible degrading genes. Methods and Results:, A bacterial strain, designated B2, capable of mineralizing MP was isolated from the MP-polluted soil. Analysis of the 16S rRNA gene sequence and phenotypic analysis suggested that strain B2 had a close relationship with Ochrobactrum anthropi. B2 could totally degrade MP and four metabolites [p -nitrophenol (PNP), 4-nitrocatechol (4-NC), 1,2,4-benzenetriol (BT) and hydroquinone (HQ)] were identified by HPLC and gas chromatography-mass spectrometry analyses. Plasmid curing of strain B2 resulted in the loss of ability of B2 to degrade PNP, but not the ability to hydrolyse MP. Conclusions:,Ochrobactrum sp. B2 can mineralize MP rapidly via PNP, 4-NC, BT and HQ pathway. B2 harbours a plasmid encoding the ability to degrade PNP, while MP-hydrolysing activity is encoded on the bacterial chromosome. Significance and Impact of the Study:, This new bacterial strain (B2) capable of mineralizing MP will be useful in a pure-culture remediation process of organophosphate pesticides and their metabolites such as nitroaromatics. [source] Expression of 3-hydroxyisobutyrate dehydrogenase in cultured neural cellsJOURNAL OF NEUROCHEMISTRY, Issue 4 2008Radovan Murín Abstract The branched-chain amino acids (BCAAs) , isoleucine, leucine, and valine , belong to the limited group of substances transported through the blood,brain barrier. One of the functions they are thought to have in brain is to serve as substrates for meeting parenchymal energy demands. Previous studies have shown the ubiquitous expression of a branched-chain alpha-keto acid dehydrogenase among neural cells. This enzyme catalyzes the initial and rate-limiting step in the irreversible degradative pathway for the carbon skeleton of valine and the other two branched-chain amino acids. Unlike the acyl-CoA derivates in the irreversible part of valine catabolism, 3-hydroxyisobutyrate could be expected to be released from cells by transport across the mitochondrial and plasma membranes. This could indeed be demonstrated for cultured astroglial cells. Therefore, to assess the ability of neural cells to make use of this valine-derived carbon skeleton as a metabolic substrate for the generation of energy, we investigated the expression in cultured neural cells of the enzyme processing this hydroxy acid, 3-hydroxyisobutyrate dehydrogenase (HIBDH). To achieve this, HIBDH was purified from bovine liver to serve as antigen for the production of an antiserum. Affinity-purified antibodies against HIBDH specifically recognized the enzyme in liver and brain homogenates. Immunocytochemistry demonstrated the ubiquitous expression of HIBDH among cultured glial (astroglial, oligodendroglial, microglial, and ependymal cells) and neuronal cells. Using an RT-PCR technique, these findings were corroborated by the detection of HIBDH mRNA in these cells. Furthermore, immunofluorescence double-labeling of astroglial cells with antisera against HIBDH and the mitochondrial marker pyruvate dehydrogenase localized HIBDH to mitochondria. The expression of HIBDH in neural cells demonstrates their potential to utilize valine imported into the brain for the generation of energy. [source] Requirement for amino acids in ontogeny of fishAQUACULTURE RESEARCH, Issue 5 2010Roderick Nigel Finn Abstract Amino acids are vital for all living organisms. During early fish ontogeny, they are important fuel molecules, signalling factors and major substrates for the synthesis of a wide range of bioactive molecules and proteins. Because the majority of fish eggs are cleidoic, i.e. closed free-living systems following ovulation and activation, early development of fish depends on the maternal provision of amino acids during oogenesis. While more than 600 proteins have been identified in the growing oocytes of fish, the major vehicles for supplying amino acids to the growing oocyte before ovulation are the vitellogenins, of which many genes and multiple forms are known. Here we review the importance of amino acids for the intermediary metabolism of fish embryos and larvae, where amino acids have been shown to be the preferred catabolic substrate. Subsequently, we address the specialization of the lysosomal pathway involved in the uptake and degradation of yolk proteins. This latter pathway is specifically modified in the germline to facilitate the long-term storage of egg yolk proteins. In marine teleosts, the degradative pathway may be activated before fertilization during oocyte maturation to release free amino acids for oocyte hydration and the acquisition of egg buoyancy. In other species, including freshwater fish, a more latent activation of acid hydrolases occurs after fertilization during the four phases of yolk resorption. The developmental contributions of the yolk syncytial layer, vitelline circulation and liver are essential components of the amino acid supply during fish ontogeny. [source] Pathogenic mutations cause rapid degradation of lysosomal storage disease-related membrane protein CLN6,HUMAN MUTATION, Issue 2 2010Anna-Katherina Kurze Abstract One variant form of late infantile neuronal ceroid lipofuscinosis is an autosomal recessive inherited neurodegenerative lysosomal storage disorder caused by mutations in the CLN6gene. The function of the polytopic CLN6 membrane protein localized in the endoplasmic reticulum is unknown. Here we report on expression studies of three mutations (c.368G>A, c.460-462delATC, c.316insC) found in CLN6 patients predicted to affect transmembrane domain 3 (p.Gly123Asp), cytoplasmic loop 2 (p.Ile154del) or result in a truncated membrane protein (p.Arg106ProfsX26), respectively. The rate of synthesis and the stability of the mutant CLN6 proteins are reduced in a mutation-dependent manner. None of the mutations prevented the dimerization of the CLN6 polypeptides. The particularly rapid degradation of the p.Arg106ProfsX26 mutant which is identical with the mutation in the murine orthologue Cln6 gene in the nclf mouse model of the disease, can be strongly inhibited by proteasomal and partially by lysosomal protease inhibitors. Both degradative pathways seem to be sufficient to prevent the accumulation/aggregation of the mutant CLN6 polypeptides in the endoplasmic reticulum. © 2009 Wiley-Liss, Inc. [source] Neuronal pigmented autophagic vacuoles: lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and diseaseJOURNAL OF NEUROCHEMISTRY, Issue 1 2008David Sulzer Abstract The most striking morphologic change in neurons during normal aging is the accumulation of autophagic vacuoles filled with lipofuscin or neuromelanin pigments. These organelles are similar to those containing the ceroid pigments associated with neurologic disorders, particularly in diseases caused by lysosomal dysfunction. The pigments arise from incompletely degraded proteins and lipids principally derived from the breakdown of mitochondria or products of oxidized catecholamines. Pigmented autophagic vacuoles may eventually occupy a major portion of the neuronal cell body volume because of resistance of the pigments to lysosomal degradation and/or inadequate fusion of the vacuoles with lysosomes. Although the formation of autophagic vacuoles via macroautophagy protects the neuron from cellular stress, accumulation of pigmented autophagic vacuoles may eventually interfere with normal degradative pathways and endocytic/secretory tasks such as appropriate response to growth factors. [source] Thermal stability of vaccinesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2003Duane T. Brandau Abstract Worldwide vaccination programs against infectious diseases and toxins are estimated to save approximately 3 million lives yearly. Tragically, however, another 3 million individuals (primarily children) die of vaccine-preven diseases. A significant portion of this problem results from the thermal instability of many of the currently used vaccines. This review argues that modern methods of physical and chemical analysis permit for the first time characterization of the degradative pathways of thermally labile vaccines. A rigorous description of these pathways permit a more rational and systematic approach to the stabilization of vaccines. A direct result of the replacement of currently employed, primarily empirical, approaches to vaccine stabilization with a more molecular-based methodology should be the development of more universally available vaccinations against life-threatening diseases. This has the potential to have a dramatic impact on world health. © 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:218,231, 2003 [source] | ||||||||||