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Catabolic Pathway (catabolic + pathway)
Selected AbstractsThe role of autophagy in , -cell lipotoxicity and type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 2010G. Las Autophagy, a ubiquitous catabolic pathway involved in both cell survival and cell death, has been implicated in many age-associated diseases. Recent findings have shown autophagy to be crucial for proper insulin secretion and , -cell viability. Transgenic mice lacking autophagy in their , -cells showed decreased , -cell mass and suppressed glucose-stimulated insulin secretion. Several studies showed that stress can stimulate autophagy in , -cells: the number of autophagosomes is increased in different in vivo models for diabetes, such as db/db mice, mice fed high-fat diet, pdx-1 knockout mice, as well as in in vitro models of glucotoxicity and lipotoxicity. Pharmacological and molecular inhibition of autophagy increases the susceptibility to cell stress, suggesting that autophagy protects against diabetes-relevant stresses. Recent findings, however, question these conclusions. Pancreases of diabetics and , -cells exposed to fatty acids show accumulation of abnormal autophagosome morphology and suppression of lysosomal gene expression suggesting impairment in autophagic turnover. In this review we attempt to give an overview of the data generated by others and by us in view of the possible role of autophagy in diabetes, a role which depending on the conditions, could be beneficial or detrimental in coping with stress. [source] Fitness drift of an atrazine-degrading population under atrazine selection pressureENVIRONMENTAL MICROBIOLOGY, Issue 3 2008Marion Devers Summary Pseudomonas sp. ADP harbouring the atrazine catabolic plasmid ADP1 was subcultured in liquid medium containing atrazine as sole source of nitrogen. After approximately 320 generations, a new population evolved which replaced the initial population. This newly evolved population grew faster and degraded atrazine more rapidly than the initial population. Plasmid profiles and Southern blot analyses revealed that the evolved strain, unlike the ancestral strain, presented a tandem duplication of the atzB gene encoding the second enzyme of the atrazine catabolic pathway responsible for the transformation of hydroxyatrazine to N-isopropylammelide. This duplication resulted from a homologous recombination that occurred between two direct repeats of 6.2 kb flanking the atzB gene and constituted by the insertion sequences IS1071, ISPps1 and a pdhL homologous sequence. This study highlights the IS-mediated plasticity of atrazine-degrading potential and demonstrates that insertion sequences not only help to disperse the atrazine-degrading gene but also improve the fitness of the atrazine-degrading population. [source] Sulfated polysaccharides inhibit the catabolism and loss of both large and small proteoglycans in explant cultures of tendonFEBS JOURNAL, Issue 15 2006Tom Samiric This study investigated the effects of two highly sulfated polysaccharides, calcium pentosan polysulfate and heparin, on the loss of newly synthesized proteoglycans from the matrix of explant cultures of bovine tendon. The tensional region of deep flexor tendon was incubated with [35S]sulfate for 6 h and then placed in culture for up to 15 days. The amount of radiolabel associated with proteoglycans lost to the medium and retained in the matrix was determined for each day in culture. It was shown that both sulfated polysaccharides at concentrations of 1000 µg·mL,1 inhibited the loss of 35S-labeled large and small proteoglycans from the matrix and concomitant with this was a retention of chemical levels of proteoglycans in the explant cultures. In other explant cultures that were maintained in culture in the presence of both agents for more than 5 days after incubation with [35S]sulfate, inhibition of the intracellular catabolic pathway was evident, indicating that these highly sulfated polysaccharides also interfered with the intracellular uptake of small proteoglycans by tendon cells. [source] Determination of the metal ion dependence and substrate specificity of a hydratase involved in the degradation pathway of biphenyl/chlorobiphenylFEBS JOURNAL, Issue 4 2005Pan Wang BphH is a divalent metal ion-dependent hydratase that catalyzes the formation of 2-keto-4-hydroxypentanoate from 2-hydroxypent-2,4-dienoate (HPDA). This reaction lies on the catabolic pathway of numerous aromatics, including the significant environmental pollutant, polychlorinated biphenyls (PCBs). BphH from the PCB degrading bacterium, Burkholderia xenoverans LB400, was overexpressed and purified to homogeneity. Atomic absorption spectroscopy and Scatchard analysis reveal that only one divalent metal ion is bound to each enzyme subunit. The enzyme exhibits the highest activity when Mg2+ was used as cofactor. Other divalent cations activate the enzyme in the following order of effectiveness: Mg2+ > Mn2+ > Co2+ > Zn2+ > Ca2+. This differs from the metal activation profile of the homologous hydratase, MhpD. UV-visible spectroscopy of the Co2+,BphH complex indicates that the divalent metal ion is hexa-coordinated in the enzyme. The nature of the metal ion affected only the kcat and not the Km values in the BphH hydration of HPDA, suggesting that cation has a catalytic rather than just a substrate binding role. BphH is able to transform alternative substrates substituted with methyl- and chlorine groups at the 5-position of HPDA. The specificity constants (kcat/Km) for 5-methyl and 5-chloro substrates are, however, lowered by eight- and 67-fold compared with the unsubstituted substrate. Significantly, kcat for the chloro-substituted substrate is eightfold lower compared with the methyl-substituted substrate, showing that electron withdrawing substituent at the 5-position of the substrate has a negative influence on enzyme catalysis. [source] Large aggregating and small leucine-rich proteoglycans are degraded by different pathways and at different rates in tendonFEBS JOURNAL, Issue 17 2004Tom Samiric This work investigated the kinetics of catabolism and the catabolic fate of the newly synthesized 35S-labelled proteoglycans present in explant cultures of tendon. Tissue from the proximal region of bovine deep flexor tendon was incubated with [35S]sulfate for 6 h and then placed in explant cultures for periods of up to 15 days. The amount of radiolabel associated with proteoglycans and free [35S]sulfate lost to the medium and retained in the matrix was determined for each day in culture. It was shown that the rate of catabolism of radiolabelled small proteoglycans (decorin and biglycan) was significantly slower (T½ > 20 days) compared with the radiolabelled large proteoglycans (aggrecan and versican) that were rapidly lost from the tissue (T½ , 2 days). Both the small and large newly synthesized proteoglycans were lost from the matrix with either intact or proteolytically modified core proteins. When explant cultures of tendon were maintained either at 4 °C or in the presence of the lysosomotrophic agent ammonium chloride, inhibition of the cellular catabolic pathway for small proteoglycans was demonstrated indicating the involvement of cellular activity and lysosomes in the catabolism of small proteoglycans. It was estimated from these studies that approximately 60% of the radiolabelled small proteoglycans that were lost from the tissue were degraded by the intracellular pathway present in tendon cells. This work shows that the pathways of catabolism for large aggregating and small leucine-rich proteoglycans are different in tendon and this may reflect the roles that these two populations of proteoglycans play in the maintenance of the extracellular matrix of tendon. [source] Indoleamine 2,3-dioxygenase in T-cell tolerance and tumoral immune escapeIMMUNOLOGICAL REVIEWS, Issue 1 2008Jessica B. Katz Summary: Indoleamine 2, 3-dioxygenase (IDO) degrades the essential amino acid tryptophan in mammals, catalyzing the initial and rate-limiting step in the de novo biosynthesis nicotinamide adenine dinucleotide (NAD). Broad evidence implicates IDO and the tryptophan catabolic pathway in generation of immune tolerance to foreign antigens in tissue microenvironments. In particular, recent findings have established that IDO is overexpressed in both tumor cells and antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the normal physiologic state, IDO is important in creating an environment that limits damage to tissues due to an overactive immune system. However, by fostering immune suppression, IDO can facilitate the survival and growth of tumor cells expressing unique antigens that would be recognized normally as foreign. In preclinical studies, small-molecule inhibitors of IDO can reverse this mechanism of immunosuppression, complementing classical cytotoxic cancer chemotherapeutic agents' ability to trigger regression of treatment-resistant tumors. These results have encouraged the clinical translation of IDO inhibitors, the first of which entered phase I clinical trials in the fall of 2007. In this article, we survey the work defining IDO as an important mediator of peripheral tolerance, review evidence of IDO dysregulation in cancer cells, and provide an overview of the development of IDO inhibitors as a new immunoregulatory treatment modality for clinical trials. [source] Degradation of isooctane by Mycobacterium austroafricanum IFP 2173: growth and catabolic pathwayJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2004F. Solano-Serena Abstract Aims:, Isooctane (2,2,4-trimethylpentane), a major component of gasoline formulations, is recalcitrant to biodegradation probably because of the quaternary carbon group it contains. Information on the biodegradability of this hydrocarbon is essential to evaluate its fate in the environment. For these reasons, the degradation kinetics and the catabolic pathway of isooctane were investigated in Mycobacterium austroafricanum IFP 2173, the only strain characterized to use it as sole carbon and energy source. Methods and Results:, The selected strain exhibited a rather moderate maximum growth rate (,max = 0·053 h,1) but degraded isooctane up to 99% with a mineralization yield of 45%, indicating attack of the quaternary carbon group. The GC/MS identification of metabolites, 2,4,4-trimethylpentanoic and dimethylpropanoic (pivalic) acids, which transiently accumulated in the cultures indicated that degradation started from the isopropyl extremity of the molecule and subsequently proceeded by catabolism of the tert -butyl moiety. The degradation of putative metabolic intermediates was investigated. The initial isooctane oxidation system was tentatively characterized. Conclusions:, The isooctane-degrading strain harboured two candidate systems for initial alkane oxidation. Although a cytochrome P450 was induced by isooctane degradation, the functional oxidation system was probably a nonheme alkane monooxygenase as indicated by PCR amplification and RT-PCR expression of an alkB gene. Significance and Impact of the Study:, Isooctane is a recalcitrant branched alkane. A plausible pathway of its degradation by Myco. austroafricanum was put forward. [source] Crystallization and preliminary crystallographic studies of human indoleamine 2,3-dioxygenaseACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 3 2006Shun-ichiro Oda Indoleamine 2,3-dioxygenase (IDO) is a haem-containing dioxygenase that catalyzes the oxidative cleavage of the pyrrole ring of indoleamines by the insertion of molecular oxygen. This reaction is the first and the rate-limiting step in the kynurenine pathway, the major Trp catabolic pathway in mammals. Recombinant human IDO was crystallized by the vapour-diffusion technique. The addition of 4-phenylimidazole as a haem ligand was essential for crystallization. The crystals belong to space group P212121, with unit-cell parameters a = 86.1, b = 98.0, c = 131.0,Å. Diffraction data were collected to 2.3,Å resolution. [source] CPT-11 Alters the Circadian Rhythm of Dihydropyrimidine Dehydrogenase mRNA in Mouse LiverCANCER SCIENCE, Issue 5 2001Mikiko Shimizu Combination chemotherapy consisting of 5-fluorouracil (5-FU) and 7-ethyl-10-[4-(l-piperidino)-l-piperidino]carboxycamptothecin (CPT-11) is a promising regimen for gastrointestinal cancer. The circadian-dependent efficacy and toxicity of 5-FU are related to the circadian variation in the activity of dihydropyrimidine dehydrogenase (DPD), which is a rate-limiting enzyme in the pyrimidine catabolic pathway. To optimize the schedule of the CPT-11 plus 5-FU combination, we investigated the effect of CPT-11 on the circadian rhythm of DPD in vivo. In control mice, the DPD mRNA level in the liver was significantly higher at 14:00 than that at 02:00. After intravenous administration of CPT-11 (30 mg/kg) at 20:00, the circadian rhythm of the DPD mRNA level in the liver was no longer observed 18 h later (14:00), but it was unaffected 6 and 18 h later (at 14:00 and 02:00) when CPT-11 was given at 08:00. In addition, a dose-dependent lengthening of the period of the circadian rhythm of DPD was observed for 42 h after intravenous injection of CPT-11 at 20:00. The levels of DPD protein and activity at 21 h after administration of CPT-11 (at 17:00) were significantly higher than at 9 h (at 05:00). These results suggest that CPT-11 may influence the circadian rhythm of DPD at the transcriptional level. Modulation of the circadian rhythm of DPD by CPT-11 may be a factor in optimizing the combination of 5-FU and CPT-11. [source] AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectivesACTA PHYSIOLOGICA, Issue 1 2009B. Viollet Abstract As the liver is central in the maintenance of glucose homeostasis and energy storage, knowledge of the physiology as well as physiopathology of hepatic energy metabolism is a prerequisite to our understanding of whole-body metabolism. Hepatic fuel metabolism changes considerably depending on physiological circumstances (fed vs. fasted state). In consequence, hepatic carbohydrate, lipid and protein synthesis/utilization are tightly regulated according to needs. Fatty liver and hepatic insulin resistance (both frequently associated with the metabolic syndrome) or increased hepatic glucose production (as observed in type 2 diabetes) resulted from alterations in substrates oxidation/storage balance in the liver. Because AMP-activated protein kinase (AMPK) is considered as a cellular energy sensor, it is important to gain understanding of the mechanism by which hepatic AMPK coordinates hepatic energy metabolism. AMPK has been implicated as a key regulator of physiological energy dynamics by limiting anabolic pathways (to prevent further ATP consumption) and by facilitating catabolic pathways (to increase ATP generation). Activation of hepatic AMPK leads to increased fatty acid oxidation and simultaneously inhibition of hepatic lipogenesis, cholesterol synthesis and glucose production. In addition to a short-term effect on specific enzymes, AMPK also modulates the transcription of genes involved in lipogenesis and mitochondrial biogenesis. The identification of AMPK targets in hepatic metabolism should be useful in developing treatments to reverse metabolic abnormalities of type 2 diabetes and the metabolic syndrome. [source] Relationships between the ethanol utilization (alc) pathway and unrelated catabolic pathways in Aspergillus nidulansFEBS JOURNAL, Issue 17 2003Michel Flipphi The ethanol utilization pathway in Aspergillus nidulans is a model system, which has been thoroughly elucidated at the biochemical, genetic and molecular levels. Three main elements are involved: (a) high level expression of the positively autoregulated activator AlcR; (b) the strong promoters of the structural genes for alcohol dehydrogenase (alcA) and aldehyde dehydrogenase (aldA); and (c) powerful activation of AlcR by the physiological inducer, acetaldehyde, produced from growth substrates such as ethanol and l -threonine. We have previously characterized the chemical features of direct inducers of the alc regulon. These studies allowed us to predict which type of carbonyl compounds might induce the system. In this study we have determined that catabolism of different amino acids, such as l -valine, l -isoleucine, l -arginine and l -proline, produces aldehydes that are either not accumulated or fail to induce the alc system. On the other hand, catabolism of d -galacturonic acid and putrescine, during which aldehydes are transiently accumulated, gives rise to induction of the alc genes. We show that the formation of a direct inducer from carboxylic esters does not depend on alcA -encoded alcohol dehydrogenase I or on AlcR, and suggest that a cytochrome P450 might be responsible for the initial formation of a physiological aldehyde inducer. [source] Methionine gamma-lyase: The unique reaction mechanism, physiological roles, and therapeutic applications against infectious diseases and cancersIUBMB LIFE, Issue 11 2009Dan Sato Abstract Sulfur-containing amino acids (SAAs) are essential components in many biological processes and ubiquitously distributed to all organisms. Both biosynthetic and catabolic pathways of SAAs are heterogeneous among organisms and between developmental stages, and regulated by the environmental changes. Limited lineage of organisms ranging from archaea to plants, but not human, possess a unique enzyme methionine gamma-lyase (MGL, EC 4.4.1.11) to directly degrade SAA to ,-keto acids, ammonia, and volatile thiols. The reaction mechanisms and the physiological roles of this enzyme are partially demonstrated by the enzymological analyzes, structure determination, isotopic labeling of the intermediate metabolites, and functional analyzes of deficient mutants. MGL has been exploited as a drug target for the infectious diseases caused by parasitic protozoa and anaerobic periodontal bacteria. In addition, MGL has been utilized to develop therapeutic interventions of various cancers, by introducing recombinant proteins to deplete methionine essential for the growth of cancer cells. In this review, we discuss the current understanding of enzymological properties, putative physiological roles, and therapeutic applications of MGL. © 2009 IUBMB IUBMB Life, 61(11): 1019,1028, 2009 [source] Subcellular distribution of key enzymes of lipid metabolism during the euthermia-hibernation-arousal cycleJOURNAL OF ANATOMY, Issue 6 2009Anna Suozzi Abstract Mammalian hibernation is a natural, fully reversible hypometabolic state characterized by a drastic reduction of body temperature and metabolic activity, which ensures survival to many species under adverse environmental conditions. During hibernation, many hibernators rely for energy supply almost exclusively on lipid reserves; the shift from carbohydrate to lipid metabolism implies profound rearrangement of the anabolic and catabolic pathways of energetic substrates. However, the structural counterpart of such adaptation is not known. In this study we investigated, by using immunoelectron microscopy, the fine intracellular distribution of two key enzymes involved in lipid metabolism, namely, the fatty acid synthase (FAS) and the long-chain fatty acyl-CoA synthetase (ACSL), in hepatocytes of euthermic, hibernating and arousing hazel dormice. Our results show that the two enzymes are differentially distributed in cellular compartments (cytoplasm, mitochondria and cell nuclei) of hepatocytes during euthermia. Quantitative redistribution of both enzymes among cellular compartments takes place during hibernation and arousal, in accordance with the physiological changes. Interestingly, this redistribution follows different seasonal patterns in cytoplasm, mitochondria and nuclei. In conclusion, our data represent the first quantitative morphological evidence of lipid enzyme distribution in a true hibernator throughout the year cycle, thus providing a structural framework to biochemical changes associated with the hypometabolism of hibernation. [source] Adaptive radiation in microbial microcosmsJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 6 2005R. CRAIG MACLEAN Abstract It has often been argued that evolutionary diversification is the result of divergent natural selection for specialization on alternative resources. I provide a comprehensive review of experiments that examine the ecology and genetics of resource specialization and adaptive radiation in microbial microcosms. In these experiments, resource heterogeneity generates divergent selection for specialization on alternative resources. At a molecular level, the evolution of specialization is generally attributable to mutations that de-regulate the expression of existing biosynthetic and catabolic pathways. Trade-offs are associated with the evolution of resource specialization, but these trade-offs are often not the result of antagonistic pleiotropy. Replicate adaptive radiations result in the evolution of a similar assemblage of specialists, but the genetic basis of specialization differs in replicate radiations. The implications of microbial selection experiments for evolutionary theory are discussed and future directions of research are proposed. [source] Comparative study between the effect of the peroxisome proliferator activated receptor-, ligands fenofibrate and n-3 polyunsaturated fatty acids on activation of 5,-AMP-activated protein kinase-,1 in high-fat fed ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2009Tarek M. Kamal Motawi Abstract Objectives Obesity is a risk factor for type 2 diabetes mellitus. It results from an energy imbalance in which energy intake exceeds energy expenditure. The cellular fuel gauge 5,-AMP-activated protein kinase (AMPK) is a heterotrimeric protein consisting of one catalytic subunit (,) and two non-catalytic subunits (, and ,), and approximately equal levels of ,1 and ,2 complexes are present in the liver. AMPK regulates metabolic pathways in response to metabolic stress and in particular ATP depletion to switch on energy-producing catabolic pathways such as ,-oxidation of fatty acids and switch off energy-depleting processes such as synthesis of fatty acid and cholesterol. A high-fat diet alters AMPK-,1 gene expression in the liver and skeletal muscle of rats and results in body weight gain and hyperglycaemia. The aim of this study was to investigate and compare the potential effects of peroxisome proliferator-activated receptor (PPAR)-, agonists fenofibrate and n-3 polyunsaturated fatty acids (PUFAs) in modulation of AMPK-,1 activity in liver and skeletal muscle of high-fat diet fed rats. Methods Reverse transcription,polymerase chain reaction was used for determination of AMPK-,1 in liver and soleus muscle and both PPAR-, and CPT-1 in hepatic tissues. Serum, total cholesterol, triacylglycerol, fatty acid and fasting blood glucose were determined colorimetrically. Key findings Both PPAR-, agonists, fenofibrate and n-3 PUFA, increased the mRNA expression of AMPK-,1 activity in liver and skeletal muscle of obese diabetic rats. Fenofibrate was superior in its activation of hepatic mRNA expression of AMPK-, 1 to exert more lipolytic effect and body weight reduction, as estimated through the decrease of triacylglycerol output and serum levels of fatty acid on the one hand and the increase in CPT-1 mRNA expression, the key enzyme in ,-oxidation of fatty acid, on the other hand. n-3 PUFA activated AMPK-,1 mRNA expression in skeletal muscle much more than fenofibrate to reveal more hypoglycaemic effect. Conclusions The PPAR-, agonists fenofibrate and n-3 PUFA could efficiently activate AMPK-,1 mRNA expression in liver and skeletal muscle to exert body weight reduction and hypoglycaemic effect, respectively. [source] Degradation of nitroaromatic compounds: a model to study evolution of metabolic pathwaysMOLECULAR MICROBIOLOGY, Issue 4 2009Maia Kivisaar Summary Although many nitroaromatic compounds have been in nature for only a few decades, bacteria have already evolved the ability to metabolize them. Both horizontal transfer of genes and mutagenesis induced under stressful conditions might facilitate evolution of new catabolic pathways. Nitrotoluene degradation pathways are supposedly derived from an ancestral naphthalene degradation pathway. The 2-nitrotoluene degradation genes in Acidovorax sp. strain JS42 are controlled by the transcriptional activator NtdR, which differs from NagR, the activator of the naphthalene degradation operon in Ralstonia sp. strain U2, by only five amino acids. Both regulators respond to salicylate, an intermediate of naphthalene degradation, but NtdR also recognizes a wide range of nitroaromatic compounds. In this issue of Molecular Microbiology, Ju et al. present results of site-directed mutagenesis of NtdR and NagR and show how the nitrotoluene-responsive regulator NtdR can be generated from a NagR-like ancestor by only a few mutations. The reconstructed hypothetical pathway for the evolution of NtdR from NagR demonstrates stepwise broadening of the effector range of the evolving protein without loss of the original activity. These results provide strong evidence for the idea that promiscuity of proteins is an important step in the evolution of new functions. [source] Agronomic and environmental implications of enhanced s -triazine degradationPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 5 2010L Jason Krutz Abstract Novel catabolic pathways enabling rapid detoxification of s -triazine herbicides have been elucidated and detected at a growing number of locations. The genes responsible for s -triazine mineralization, i.e. atzABCDEF and trzNDF, occur in at least four bacterial phyla and are implicated in the development of enhanced degradation in agricultural soils from all continents except Antarctica. Enhanced degradation occurs in at least nine crops and six crop rotation systems that rely on s -triazine herbicides for weed control, and, with the exception of acidic soil conditions and s -triazine application frequency, adaptation of the microbial population is independent of soil physiochemical properties and cultural management practices. From an agronomic perspective, residual weed control could be reduced tenfold in s -triazine-adapted relative to non-adapted soils. From an environmental standpoint, the off-site loss of total s -triazine residues could be overestimated 13-fold in adapted soils if altered persistence estimates and metabolic pathways are not reflected in fate and transport models. Empirical models requiring soil pH and s -triazine use history as input parameters predict atrazine persistence more accurately than historical estimates, thereby allowing practitioners to adjust weed control strategies and model input values when warranted. Published in 2010 by John Wiley & Sons, Ltd. [source] Expanding roles for AMP-activated protein kinase in neuronal survival and autophagyBIOESSAYS, Issue 9 2009Jeroen Poels Abstract AMP-activated protein kinase (AMPK) is an evolutionarily conserved cellular switch that activates catabolic pathways and turns off anabolic processes. In this way, AMPK activation can restore the perturbation of cellular energy levels. In physiological situations, AMPK senses energy deficiency (in the form of an increased AMP/ATP ratio), but it is also activated by metabolic insults, such as glucose or oxygen deprivation. Metformin, one of the most widely prescribed anti-diabetic drugs, exerts its actions by AMPK activation. However, while the functions of AMPK as a metabolic regulator are fairly well understood, its actions in neuronal cells only recently gained attention. This review will discuss newly emerged functions of AMPK in neuroprotection and neurodegeneration. Additionally, recent views on the role of AMPK in autophagy, an important catabolic process that is also involved in neurodegeneration and cancer, will be highlighted. [source] Chapter 6: Maize with Increased Lysine (Lysine Maize,LY038)COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY, Issue 1 2008Article first published online: 30 JAN 200 ABSTRACT:, Data and information provided in this case study relate to a crop derived by modern biotechnology, in which a specific nutrient (lysine) has been increased in maize grain.Lysine maize is a feed ingredient with enhanced nutritional characteristics for poultry and swine and provides an alternative to adding supplemental lysine to diets for these animals. Lysine maize is in an advanced state of development; therefore, extensive unpublished data and information are presented to demonstrate that (1) Lysine maize,and the feeds and foods derived from it,are as safe as those derived from conventional maize,and (2) the increased lysine in Lysine maize grain produces the intended nutritional benefit for broiler chickens when compared to a diet containing conventional maize grain and a crystalline lysine supplement. These conclusions are based on a detailed molecular characterization of Lysine maize,a safety assessment of the introduced protein,a safety and nutritional assessment of the LY038 crop,and a comparison of the agronomic and phenotypic properties of maize hybrids with and without the Lysine maize trait. Although Lysine maize is a specialty crop for use in animal feed,its safety for both animals and humans must be demonstrated. Free lysine is significantly increased in Lysine maize by the introduction of the dapA gene (cordapA) from Corynebacterium glutamicum that encodes a form of dihydrodipicolinate synthase (cDHDPS) that is insensitive to lysine feedback inhibition.Analysis of lysine anabolic and catabolic pathways in maize identified 6 metabolites that might change as a consequence of the introduction of cDHDPS insensitive to lysine-feedback inhibition. The results of compositional analysis demonstrated that Lysine maize grain is comparable to conventional maize, with the exception of the intended increase in lysine and a corresponding increase in 2 products of lysine catabolism,saccha-ropine and -aminoadipic acid. Therefore, the safety and/or nutritional implication of these 3 compounds under the conditions of use were the focus of additional assessments and found to not present either a safety or nutritional problem. [source] | ||||||||||||||||