Letteratura scientifica selezionata sul tema "VLFCA"
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Articoli di riviste sul tema "VLFCA"
1
Zhou, Jie, Marcia R. Terluk, Paul J. Orchard, James C. Cloyd e Reena V. Kartha. "N-Acetylcysteine Reverses the Mitochondrial Dysfunction Induced by Very Long-Chain Fatty Acids in Murine Oligodendrocyte Model of Adrenoleukodystrophy". Biomedicines 9, n. 12 (3 dicembre 2021): 1826. http://dx.doi.org/10.3390/biomedicines9121826.
Testo completoAbstract (sommario):
The accumulation of saturated very long-chain fatty acids (VLCFA, ≥C22:0) due to peroxisomal impairment leads to oxidative stress and neurodegeneration in X-linked adrenoleukodystrophy (ALD). Among the neural supporting cells, myelin-producing oligodendrocytes are the most sensitive to the detrimental effect of VLCFA. Here, we characterized the mitochondrial dysfunction and cell death induced by VLFCA, and examined whether N-acetylcysteine (NAC), an antioxidant, prevents the cytotoxicity. We exposed murine oligodendrocytes (158 N) to hexacosanoic acid (C26:0, 1–100 µM) for 24 h and measured reactive oxygen species (ROS) and cell death. Low concentrations of C26:0 (≤25 µM) induced a mild effect on cell survival with no alterations in ROS or total glutathione (GSH) concentrations. However, analysis of the mitochondrial status of cells treated with C26:0 (25 µM) revealed depletion in mitochondrial GSH (mtGSH) and a decrease in the inner membrane potential. These results indicate that VLCFA disturbs the mitochondrial membrane potential causing ROS accumulation, oxidative stress, and cell death. We further tested whether NAC (500 µM) can prevent the mitochondria-specific effects of VLCFA in C26:0-treated oligodendrocytes. Our results demonstrate that NAC improves mtGSH levels and mitochondrial function in oligodendrocytes, indicating that it has potential use in the treatment of ALD and related disorders.
2
McGuinness, M. C., J. F. Lu, H. P. Zhang, G. X. Dong, A. K. Heinzer, P. A. Watkins, J. Powers e K. D. Smith. "Role of ALDP (ABCD1) and Mitochondria in X-Linked Adrenoleukodystrophy". Molecular and Cellular Biology 23, n. 2 (15 gennaio 2003): 744–53. http://dx.doi.org/10.1128/mcb.23.2.744-753.2003.
Testo completoAbstract (sommario):
ABSTRACT Peroxisomal disorders have been associated with malfunction of peroxisomal metabolic pathways, but the pathogenesis of these disorders is largely unknown. X-linked adrenoleukodystrophy (X-ALD) is associated with elevated levels of very-long-chain fatty acids (VLCFA; C>22:0) that have been attributed to reduced peroxisomal VLCFA β-oxidation activity. Previously, our laboratory and others have reported elevated VLCFA levels and reduced peroxisomal VLCFA β-oxidation in human and mouse X-ALD fibroblasts. In this study, we found normal levels of peroxisomal VLCFA β-oxidation in tissues from ALD mice with elevated VLCFA levels. Treatment of ALD mice with pharmacological agents resulted in decreased VLCFA levels without a change in VLCFA β-oxidation activity. These data indicate that ALDP does not determine the rate of VLCFA β-oxidation and that VLCFA levels are not determined by the rate of VLCFA β-oxidation. The rate of peroxisomal VLCFA β-oxidation in human and mouse fibroblasts in vitro is affected by the rate of mitochondrial long-chain fatty acid β-oxidation. We hypothesize that ALDP facilitates the interaction between peroxisomes and mitochondria, resulting, when ALDP is deficient in X-ALD, in increased VLCFA accumulation despite normal peroxisomal VLCFA β-oxidation in ALD mouse tissues. In support of this hypothesis, mitochondrial structural abnormalities were observed in adrenal cortical cells of ALD mice.
3
Siigur, Jüri, Katrin Trummal, Külli TÕnismägi, Mari Samel, Ene Siigur, Heikki Vija, Indrek Tammiste e Juhan Subbi. "Use of MALDI-TOF Mass Spectrometry for Specificity Studies of Biomedically Important Proteases". Spectroscopy 16, n. 3-4 (2002): 161–70. http://dx.doi.org/10.1155/2002/204307.
Testo completoAbstract (sommario):
Proteases play crucial role starting from fertilization until to cell death. Our studies of the two Viperidae venoms (Levantine viperVipera lebetina, Common viperVipera berus) have demonstrated the existence of biomedically important proteases, both coagulants and anticoagulants that may be useful as diagnostic tools or potential therapeutics. We showed that venoms of both snakes contain: (i) metalloproteases and serine proteases that degrade fibrinogen, but not fibrin; (ii) factor X activators (VLFXA, VBFXAE); (iii) bradykinin-releasing serine proteases. AdditionallyVipera lebetinasnake venom contains thrombolytic fibrin degrading metalloenzyme (lebetase), HUVEC cell apoptosis inducing metalloprotease (VLAIP), factor V activator (VLFVA), thermostable β-fibrinogenase and α-fibrinogenase which has no homolog among known serine proteases. We examined the activity of snake venom proteases against bradykinin, substance P, insulin B-chain and 6–10 amino acid residues containing peptides synthesized according to potential cleavage regions of fibrinogen, factor X, factor IX, factor V, α2-macroglobulin bait region and pregnancy zone protein (PZP). We used MALDI TOF mass spectrometry technique for the discovery and identification of peptides released by protease hydrolysis. The sensitive and quick MALDI-TOF mass spectrometry methodology allows us to obtain the primary information about the substrate specificity of different proteases against various peptides and proteins.
4
Batsale, Marguerite, Delphine Bahammou, Laetitia Fouillen, Sébastien Mongrand, Jérôme Joubès e Frédéric Domergue. "Biosynthesis and Functions of Very-Long-Chain Fatty Acids in the Responses of Plants to Abiotic and Biotic Stresses". Cells 10, n. 6 (21 maggio 2021): 1284. http://dx.doi.org/10.3390/cells10061284.
Testo completoAbstract (sommario):
Very-long-chain fatty acids (i.e., fatty acids with more than 18 carbon atoms; VLCFA) are important molecules that play crucial physiological and structural roles in plants. VLCFA are specifically present in several membrane lipids and essential for membrane homeostasis. Their specific accumulation in the sphingolipids of the plasma membrane outer leaflet is of primordial importance for its correct functioning in intercellular communication. VLCFA are found in phospholipids, notably in phosphatidylserine and phosphatidylethanolamine, where they could play a role in membrane domain organization and interleaflet coupling. In epidermal cells, VLCFA are precursors of the cuticular waxes of the plant cuticle, which are of primary importance for many interactions of the plant with its surrounding environment. VLCFA are also major components of the root suberin barrier, which has been shown to be fundamental for nutrient homeostasis and plant adaptation to adverse conditions. Finally, some plants store VLCFA in the triacylglycerols of their seeds so that they later play a pivotal role in seed germination. In this review, taking advantage of the many studies conducted using Arabidopsis thaliana as a model, we present our current knowledge on the biosynthesis and regulation of VLCFA in plants, and on the various functions that VLCFA and their derivatives play in the interactions of plants with their abiotic and biotic environment.
5
Zhukov, Anatoly, e Valery Popov. "Synthesis of C20–38 Fatty Acids in Plant Tissues". International Journal of Molecular Sciences 23, n. 9 (25 aprile 2022): 4731. http://dx.doi.org/10.3390/ijms23094731.
Testo completoAbstract (sommario):
Very-long-chain fatty acids (VLCFA) are involved in a number of important plant physiological functions. Disorders in the expression of genes involved in the synthesis of VLCFA lead to a number of phenotypic consequences, ranging from growth retardation to the death of embryos. The elongation of VLCFA in the endoplasmic reticulum (ER) is carried out by multiple elongase complexes with different substrate specificities and adapted to the synthesis of a number of products required for a number of metabolic pathways. The information about the enzymes involved in the synthesis of VLCFA with more than 26 atoms of Carbon is rather poor. Recently, genes encoding enzymes involved in the synthesis of both regular-length fatty acids and VLCFA have been discovered and investigated. Polyunsaturated VLCFA in plants are formed mainly by 20:1 elongation into new monounsaturated acids, which are then imported into chloroplasts, where they are further desaturated. The formation of saturated VLCFA and their further transformation into a number of aliphatic compounds included in cuticular waxes and suberin require the coordinated activity of a large number of different enzymes.
6
Zhukov, Anatoly, e Valery Popov. "Synthesis of C20–38 Fatty Acids in Plant Tissues". International Journal of Molecular Sciences 23, n. 9 (25 aprile 2022): 4731. http://dx.doi.org/10.3390/ijms23094731.
Testo completoAbstract (sommario):
Very-long-chain fatty acids (VLCFA) are involved in a number of important plant physiological functions. Disorders in the expression of genes involved in the synthesis of VLCFA lead to a number of phenotypic consequences, ranging from growth retardation to the death of embryos. The elongation of VLCFA in the endoplasmic reticulum (ER) is carried out by multiple elongase complexes with different substrate specificities and adapted to the synthesis of a number of products required for a number of metabolic pathways. The information about the enzymes involved in the synthesis of VLCFA with more than 26 atoms of Carbon is rather poor. Recently, genes encoding enzymes involved in the synthesis of both regular-length fatty acids and VLCFA have been discovered and investigated. Polyunsaturated VLCFA in plants are formed mainly by 20:1 elongation into new monounsaturated acids, which are then imported into chloroplasts, where they are further desaturated. The formation of saturated VLCFA and their further transformation into a number of aliphatic compounds included in cuticular waxes and suberin require the coordinated activity of a large number of different enzymes.
7
Bourassa, Dianna V., Elmar L. Kannenberg, D. Janine Sherrier, R. Jeffrey Buhr e Russell W. Carlson. "The Lipopolysaccharide Lipid A Long-Chain Fatty Acid Is Important for Rhizobium leguminosarum Growth and Stress Adaptation in Free-Living and Nodule Environments". Molecular Plant-Microbe Interactions® 30, n. 2 (febbraio 2017): 161–75. http://dx.doi.org/10.1094/mpmi-11-16-0230-r.
Testo completoAbstract (sommario):
Rhizobium bacteria live in soil and plant environments, are capable of inducing symbiotic nodules on legumes, invade these nodules, and develop into bacteroids that fix atmospheric nitrogen into ammonia. Rhizobial lipopolysaccharide (LPS) is anchored in the bacterial outer membrane through a specialized lipid A containing a very long-chain fatty acid (VLCFA). VLCFA function for rhizobial growth in soil and plant environments is not well understood. Two genes, acpXL and lpxXL, encoding acyl carrier protein and acyltransferase, are among the six genes required for biosynthesis and transfer of VLCFA to lipid A. Rhizobium leguminosarum mutant strains acpXL, acpXL−/lpxXL−, and lpxXL− were examined for LPS structure, viability, and symbiosis. Mutations in acpXL and lpxXL abolished VLCFA attachment to lipid A. The acpXL mutant transferred a shorter acyl chain instead of VLCFA. Strains without lpxXL neither added VLCFA nor a shorter acyl chain. In all strains isolated from nodule bacteria, lipid A had longer acyl chains compared with laboratory-cultured bacteria, whereas mutant strains displayed altered membrane properties, modified cationic peptide sensitivity, and diminished levels of cyclic β-glucans. In pea nodules, mutant bacteroids were atypically formed and nitrogen fixation and senescence were affected. The role of VLCFA for rhizobial environmental fitness is discussed.
8
Robinson, B. S., D. W. Johnson e A. Poulos. "Unique molecular species of phosphatidylcholine containing very-long-chain (C24-C38) polyenoic fatty acids in rat brain". Biochemical Journal 265, n. 3 (1 febbraio 1990): 763–67. http://dx.doi.org/10.1042/bj2650763.
Testo completoAbstract (sommario):
Rat brain has been shown to contain polyenoic very-long-chain fatty acids (VLCFA) belonging to the n-3 and n-6 series with four, five and six double bonds and even-carbon chain lengths from 24 to 38. These fatty acids are almost exclusively located in unusual molecular species of phosphatidylcholine at the sn-1 position of the glycerol backbone, whereas saturated, monoenoic and polyenoic fatty acids with less than 24 carbon atoms are present at the sn-2 position. Polyenoic VLCFA phosphatidylcholine in neonatal rat brain is enriched with n-6 pentaenoic and n-3 hexaenoic VLCFA with up to 36 carbon atoms, whereas the corresponding phospholipid in adult rat brain mainly contains n-6 tetraenoic and n-3 pentaenoic VLCFA with up to 38 carbon atoms. The total amount of polyenoic VLCFA associated with phosphatidylcholine is highest in the brain of immature animals. Polyenoic VLCFA phosphatidylcholine appears to be predominantly confined to nervous tissue in rats, and it is envisaged that this phospholipid is of physiological significance.
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Trinh, Duy-Chi, Julien Lavenus, Tatsuaki Goh, Yohann Boutté, Quentin Drogue, Virginie Vaissayre, Frédérique Tellier et al. "PUCHI regulates very long chain fatty acid biosynthesis during lateral root and callus formation". Proceedings of the National Academy of Sciences 116, n. 28 (24 giugno 2019): 14325–30. http://dx.doi.org/10.1073/pnas.1906300116.
Testo completoAbstract (sommario):
Lateral root organogenesis plays an essential role in elaborating plant root system architecture. InArabidopsis, the AP2 family transcription factor PUCHI controls cell proliferation in lateral root primordia. To identify potential targets of PUCHI, we analyzed a time course transcriptomic dataset of lateral root formation. We report that multiple genes coding for very long chain fatty acid (VLCFA) biosynthesis enzymes are induced during lateral root development in a PUCHI-dependent manner. Significantly, several mutants perturbed in VLCFA biosynthesis show similar lateral root developmental defects aspuchi-1. Moreover,puchi-1roots display the same disorganized callus formation phenotype as VLCFA biosynthesis-deficient mutants when grown on auxin-rich callus-inducing medium. Lipidomic profiling ofpuchi-1roots revealed reduced VLCFA content compared with WT. We conclude that PUCHI-regulated VLCFA biosynthesis is part of a pathway controlling cell proliferation during lateral root and callus formation.
10
Williams, John, Kan Zhu, Eric Crampon e André Iffland. "Fit-for-purpose biomarker LC–MS/MS qualification for the quantitation of very long chain fatty acids in human cerebrospinal fluid". Bioanalysis 12, n. 3 (febbraio 2020): 143–58. http://dx.doi.org/10.4155/bio-2019-0256.
Testo completoAbstract (sommario):
Aim: Very long chain fatty acids (VLCFAs) have been identified as biomarkers for several peroxisomal disorders necessitating the need for reliable biomarker assays in particular C20, C22, C24, C26 in cerebrospinal fluid (CSF). Until now no absolute quantitation assay for total VLCFAs in CSF has been successfully developed and qualified for clinical use. Methodology: A quantitative LC–MS/MS assay for total VLCFA in human CSF was developed. Derivatization tag and coupling chemistry were optimized for sensitivity. CSF contamination by blood, non-specific binding of VLCFA to surfaces and exogenous VLCFA contamination was minimized. Discussion/conclusion: This fit for purpose biomarker assay was used to measure baseline healthy human VLCFA levels across multiple subjects to establish an understanding of concentration ranges and feasibility.
Tesi sul tema "VLFCA"
1
Le, ruyet Claire. "Investigating herbicide targets in the very long-chain fatty acid biosynthesis pathway". Electronic Thesis or Diss., Bordeaux, 2024. http://www.theses.fr/2024BORD0125.
Testo completoAbstract (sommario):
Les acides gras à très longue chaîne (AGTLC) sont des molécules essentielles avec des fonctions physiologiques et structurales importantes chez les plantes. Ces acides gras, qui ont des chaînes acyles de 20 carbones ou plus, peuvent être modifiés en composants de lipides clés tels que les phospholipides et les sphingolipides des membranes, les triacylglycérols (TAG) dans les graines, les cires cuticulaires dans l'épiderme et la subérine dans les racines. L'élongation des AGTLC est réalisée par le complexe d'élongation des acides gras (FAE complex). Ce complexe comprend quatre enzymes distinctes ancrées à la membrane du réticulum endoplasmique (RE) : KCS, KCR, HCD et ECR. Le complexe FAE réalise un cycle de réaction en quatre étapes qui ajoute deux carbones à la chaîne pour allonger la chaine acyl. L'enzyme KCS est responsable de la première réaction, qui implique une condensation entre un malonyl-CoA et un acyl-CoA. Les enzymes KCS sont connues pour leur grande diversité génétique chez les plantes, et la caractérisation fonctionnelle de plusieurs gènes AtKCS a révélé différentes spécificités de substrat. Cela suggère que la sélectivité de la longueur de chaîne des complexes FAE est déterminée par la sous-unité KCS du complexe. Les herbicides qui inhibent la synthèse des AGTLC (groupe HRAC 15), tels que le flufenacet, le pyroxasulfone ou les chloroacétamides, jouent un rôle crucial dans les stratégies de gestion des mauvaises herbes. Le mode d'action de ces composés a été initialement identifié sur la base du phénotype caractéristique observé chez les plantes traitées, suggérant une inhibition de la synthèse des VLCFA. Dans ce processus d'inhibition, plusieurs herbicides ciblent la sous-unité KCS des complexes FAE. Des essais enzymatiques in vitro ont démontré l'inhibition de la KCS par divers herbicides, cependant, plusieurs autres herbicides, qui induisent un phénotype similaire chez les plantes, ne semblent pas inhiber l'enzyme KCS et leurs cibles moléculaires restent inconnues. La plupart des herbicides disponibles dans le commerce présentent une activité plus forte contre les plantes herbacées (monocotylédones) que contre les plantes à feuilles larges (dicotylédones), bien que les raisons de cette sélectivité ne soient pas bien comprises. L'objectif de ce projet de doctorat était d'explorer davantage l'inhibition de la synthèse des AGTLC. Pour ce faire, une analyse phylogénétique et une analyse fonctionnelle comparative de la KCS provenant de diverses espèces végétales ont été réalisées en utilisant un système hétérologue de levure reconstituant le complexe FAE complet de la plante. De plus, des études in vivo utilisant la levure exprimant des KCS actives traitées avec plusieurs herbicides ont été menées pour étudier leur mode d'action et leur sélectivité. Enfin, un essai in vitro sans radioactivité a été développé pour évaluer l'activité de la KCS et l'inhibition par les herbicides du groupe HRAC 15Very-long-chain fatty acids (VLCFA) are essential molecules with significant physiological and structural functions in plants. These fatty acids, which have acyl chains of 20 or more carbons, can be modified into components of key lipids such as phospholipids and sphingolipids of membranes, triacylglycerols (TAGs) in seeds, cuticular waxes in the epidermis, and suberin in roots.The elongation of VLCFA is carried out by the Fatty Acid Elongase complex (FAE complex). This complex comprises four distinct enzymes anchored to the endoplasmic reticulum (ER) membrane: KCS, KCR, HCD, and ECR. The FAE complex performs a four-step reaction cycle that adds two carbons to elongate the fatty acyl chain. The KCS enzyme is responsible for the first reaction, which involves a condensation between a malonyl-CoA and an acyl-CoA. KCS enzymes are known for their high genetic diversity in plants, and functional characterization of several AtKCS genes has revealed different substrate specificities. This suggests that the chain length selectivity of FAE complexes is determined by the KCS subunit of the complex.Herbicides that inhibit VLCFA synthesis (HRAC group 15), such as flufenacet, pyroxasulfone, or chloroacetamides, play a crucial role in weed management strategies. The mode of action of these compounds was initially identified based on the characteristic phenotype observed in treated plants, suggesting inhibition of VLCFA synthesis. In this inhibition process, several herbicides target the KCS subunit of the FAE complexes (Trenkamp et al., 2003). In vitro enzymatic assays have demonstrated inhibition of KCS by various herbicides, however, several other herbicides, that induce similar phenotype in plants, do not appear to inhibit the KCS enzyme and their molecular targets remain unknown. Most commercially available herbicides exhibit stronger activity against grass plants (monocotyledonous) than broadleaf plants (dicotyledonous), though the reasons for this selectivity are not well understood.The objective of this PhD project was to further explore the inhibition of VLCFA synthesis. To do so, a phylogenetic analysis and a comparative functional analysis of KCS from various plant species were performed using a yeast heterologous system reconstituting the complete plant FAE complex. In addition, in vivo studies using yeast expressing active KCSs treated with several herbicides were conducted to investigate their mode of action and selectivity. Finally, a non-radiolabeled in vitro assay was developed to evaluate KCS activity and inhibition by HRAC 15 group herbicide
2
Hay, Marshall Mark. "Control of Palmer amaranth (Amaranthus palmeri) and common waterhemp (Amaranthus rudis) in double crop soybean and with very long chain fatty acid inhibitor herbicides". Thesis, Kansas State University, 2017. http://hdl.handle.net/2097/35489.
Testo completoAbstract (sommario):
Master of ScienceDepartment of Agronomy
Dallas E. Peterson
During 2015 and 2016, five site years of research were implemented in double crop soybean after winter wheat at experiment fields in Kansas near Manhattan, Hutchinson, and Ottawa to assess various non-glyphosate herbicide treatments at three different application timings for control of Palmer amaranth (Amaranthus palmeri S. Wats.) and common waterhemp (Amaranthus rudis Sauer). Spring-post (SP) treatments with residual control of Palmer amaranth and waterhemp were applied in the winter wheat at Feekes 4 and resulted in less than 50% control of Palmer amaranth and waterhemp at the time of double crop soybean planting. Pre-harvest treatments were applied two weeks before winter wheat harvest. 2,4-D resulted in highly variable Palmer amaranth and waterhemp control whereas flumioxazin resulted in comparable control to PRE treatments that contained paraquat plus a residual herbicide. Excellent Palmer amaranth and waterhemp control was observed at 1 week after planting (WAP) double crop soybean with a preemergence (PRE) paraquat application; however, reduced control of Palmer amaranth and waterhemp was noted at 8WAP due to extended emergence. Palmer amaranth and waterhemp control was 85% or greater at 8WAP for most PRE treatments that included a combination of paraquat plus residual herbicides. PRE treatments that did not include the combination of paraquat and residual herbicides did not provide acceptable control. A second set of field experiments were established in 2015 and 2016 near Manhattan, Hutchinson, and Ottawa to assess residual Palmer amaranth and waterhemp control with very-long-chain-fatty acid (VLFCA) inhibiting herbicides. Acetochlor (non-encapsulated and encapsulated), alachlor, dimethenamid-P, metolachlor, S-metolachlor, and pyroxasulfone as well as the microtubule inhibiting herbicide pendimethalin were applied at three different field use rates (high, middle, and low) based on labeled rate ranges for soybean as PRE treatments in a non-crop scenario after the plot was clean tilled with a field cultivator. The experiment was conducted one time in 2015 and four times in 2016 at two different locations for a total of five site years of data. PRE applications were made June 1, 2015, near Manhattan. PRE applications in 2016 were made in April at locations near Hutchinson and Ottawa; the second run of the experiment was applied in June at the same locations on a different set of plot areas. At Manhattan pyroxasulfone, S-metolachlor, and dimethenamid-P resulted in the highest Palmer amaranth control at 4WAT. At Hutchinson, pyroxasulfone resulted in superior Palmer amaranth control compared to dimethenamid-P and pendimethalin at 4WAT and 8WAT. At Ottawa, acetochlor, S-metolachlor, and pyroxasulfone resulted in higher waterhemp control than alachlor and pendimethalin at 4WAT and 8WAT.
3
Morineau, Céline. "Caractérisation d'un nouveau membre du complexe d'élongation des acides gras chez Arabidopsis thaliana : intéractions métaboliques et régulation développementale". Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112420.
Testo completoAbstract (sommario):
Les acides gras à très longues chaine (VLCFA) sont essentiels dans le développement, particulièrement dans les mécanismes de trafic vésiculaires, de différenciation et division cellulaire. Cependant, le rôle de ces VLCFA dans ces différents processus chez les plantes n’est pas encore bien compris. Afin d’identifier de nouveaux acteurs associés à la biosynthèse ou la fonction des VLCFA, un crible suppresseur multicopies a été réalisé dans un mutant d’élongation des VLCFA de levure. La perte de l’activité déshydratase PHS1 chez la levure et de PASTICCINO2 chez les plantes perturbe la croissance et induit des défauts de cytokinèse. La PROTEIN TYROSIN PHOSPHATASE-LIKE (PTPLA) historiquement caractérisée comme une déshydratase inactive est capable de restaurer les défauts de croissance et d’élongation de phs1 mais non de pas2. PTPLA interagit avec plusieurs membres du complexe élongase dans le RE et son absence conduit à l’accumulation 3-hydroxyacyl-CoA, signature des déshydratases impliquées dans l’élongation des acides gras. Cependant, la perte de PTPLA conduit à une augmentation des VLCFA, probablement dépendante de PAS2 montrant que PTPLA serait un répresseur potentiel de l’élongation. Les deux déshydratases ont des profils d’expression divergents dans la racine. PAS2 est majoritairement exprimé dans l’endoderme tandis que PTPLA s’exprime uniquement dans les tissus vasculaires et le péricycle. La comparaison de l’expression ectopique de PAS2 et PTPLA dans leur tissus respectif confirme l’existence de deux complexe élongase indépendant associé à PAS2 ou PTPLA et interagissant de manière non cellule autonome. Les cytokinines pourraient constituer le signal entre les deux complexes élongase du fait que la biosynthèse de ces hormones est réprimée par les VLCFA. Les VLCFA répriment ainsi l'expression d'IPT3 dans les racines comme observées pour la partie apicale. Les cytokinines semblent aussi réguler la teneur en VLCFA dans la racine suggérant la présence de boucles de rétrocontrôles entre ces hormones et les VLCFAVery long chain fatty acids (VLCFA) are involved in plant development and particularly in several cellular processes such as membrane trafficking, cell division and cell differentiation. However, the precise role of VLCFA in these different cellular processes is still poorly understood in plants. In order to identify new factors associated with the biosynthesis or function of VLCFA, a yeast multicopy suppressor screen was carried out in a yeast mutant strain defective for fatty acid elongation. Loss of function of the elongase dehydratase PHS1 in yeast and PASTICCINO2 in plants prevents growth and induces cytokinesis defects. PROTEIN TYROSIN PHOSPHATASE-LIKE (PTPLA) previously characterized as an inactive dehydratase was able to restore yeast phs1 growth and VLCFA elongation but not the plant pas2 defects. PTPLA interacted with elongase members in the ER and its absence induced the accumulation of 3-hydroxyacyl-CoA as expected from a dehydratase involved in fatty acid (FA) elongation. However, loss of PTPLA function led to increased VLCFA levels, effect that was dependent of the presence of PAS2 indicating that PTPLA activity repressed FA elongation. The two dehydratases have specific expression profiles in the root with PAS2, mostly restricted in the endodermis, while PTPLA was confined in the vascular tissue and pericycle cells. Comparative ectopic expression of PTPLA and PAS2 in their respective domains confirmed the existence of two independent elongase complexes comprising PAS2 or PTPLA that were functionally interacting in a non-cell autonomous manner. A putative regulating signal could involve cytokinins that were described to be regulated by VLCFA. VLCFA were indeed found to repress IPT3 expression in roots like in leaves. Cytokinins were also found to regulate VLCFA levels suggesting the existence of regulatory feedback loops between cytokinins and VLCFA
4
Marlow, Victoria L. "Investigating bacterial factors important for the sinorhizobium meliloti-legume symbiosis". Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4331.
Testo completoAbstract (sommario):
In both the legume symbiont Sinorhizobium meliloti and the mammalian pathogen Brucella abortus, the inner membrane BacA protein is essential for host persistence. In free-living S. meliloti and B. abortus loss of the BacA protein also results in an increased resistance to the glycopeptide bleomycin and a ~ 50% decrease in the lipopolysaccharide (LPS) very-long-chain-fatty-acid (VLCFA) content. Consequently, it was proposed that BacA may be involved in transport of peptides into the cell and/or that BacA may be involved in the VLCFA modification of the LPS. During this work it was determined that the increased resistance observed in an S. meliloti DbacA mutant to bleomycin and to the truncated eukaryotic peptide Bac7(1-16), is independent of the VLCFA modification. These data support a model for BacA having multiple non-overlapping functions. Using flow cytometry studies with fluorescently labelled forms of bleomycin and Bac7(1-16) it was found that the BacA protein plays a role in the uptake of bleomycin. However, BacA was shown to be essential for the uptake of Bac7(1-16). Additionally, it was determined that two symbiotically defective bacA site directed mutants with known reductions in their VLCFA could still take up Bac7, suggesting that the BacA function that leads to the VLCFA modification could also play a key role in host persistence. To investigate further the role of BacA in the VLCFA modification and where in the cell envelope the lipid A is modified with the VLCFA, the role of the putative lipid trafficking protein MsbA2 was investigated. Interestingly, it was discovered that S. meliloti lacking the MsbA2 protein, is unable to enter host cells and induces a plant defence response more characteristic of a pathogen. To investigate the importance of the VLCFA modification during the symbiosis S. meliloti mutants lacking either the AcpXL (VLCFA acyl carrier protein) or LpxXL (VLCFA acyl transferase protein) were characterized in the host. Although not essential for host persistence, loss of each of the proteins did result in distinct defects, suggesting the VLCFA modification is important during the symbiosis. Since there are hundreds of nodule specific cysteine-rich peptides produced by the host plant Medicago truncatula, the BacA mediated uptake of one of these peptides combined with the VLCFA modification may account for the essential role of the BacA protein in the legume symbiosis.
5
El, Hajj Hammam. "Altérations mitochondriales et processus inflammatoire dans la déficience en acyl- Coenzyme A oxydase 1 peroxysomale". Phd thesis, Université de Bourgogne, 2012. http://tel.archives-ouvertes.fr/tel-00995795.
Testo completoAbstract (sommario):
L'acyl-CoA oxydase 1 (ACOX1) est l'enzyme qui catalyse la première étape de la voie classique de la β-oxydation peroxysomale. Cette voie catabolise exclusivement les acides gras à très longue chaîne (AGTLC). Chez l'homme, la déficience en ACOX1 est à l'origine de la pseudo adrénoleucodystrophie néonatale (P-NALD), une maladie neurodégénérative rare caractérisée par une accumulation des AGTLC dans le plasma et les tissus, une hépatomégalie, un retard du développement moteur et une démyélinisation de la matière blanche cérébrale. Chez la souris, l'extinction du gène Acox1 provoque une accumulation des AGTLC dans le plasma, un retard de croissance, une stéatose hépatique et le développement d'une hépatocarcinogenèse avec l'âge. Cependant, ces souris ne développent pas de symptômes cérébraux contrairement aux patients P NALD. Au cours de ce travail, on a pu montrer sur des fibroblastes issus de patients atteints de P NALD qu'en absence d'activité ACOX1, les peroxysomes sont diminués en nombre et augmentés en taille avec un niveau de β-oxydation peroxysomale fortement réduit. L'accumulation des AGTLC suite à la déficience en ACOX1 dans ces cellules provoque, au niveau transcriptionnel, la perturbation de la voie de synthèse du cholestérol et déclenche une réaction inflammatoire caractérisée par l'activation de la voie de l'IL-1 et la sécrétion d'IL-6 et d'IL-8. Le rôle métabolique important que joue l'ACOX1 dans l'homéostasie énergétique cellulaire a pu être souligné chez l'homme et chez la souris. En effet, la déficience en ACOX1 dans les fibroblastes de patients P-NALD perturbe la morphologie de la mitochondrie qui apparaît anormale ainsi que le métabolisme énergétique mitochondrial caractérisé par une inhibition de PGC-1α par acétylation, une surexpression de l'activité du complexe V et une diminution du taux d'ATP mitochondrial. L'absence dans le foie de l'activité ACOX1, chez la souris Acox1-/-, se traduit par des perturbations, au niveau mitochondrial, dela biogenèse et du métabolisme énergétique. Ces perturbations mitochondriales se caractérisent par une diminution de l'activité du complexe IV de la chaîne respiratoire accompagnée d'une diminution de la respiration. Cependant, ces perturbations n'affectent pas le taux d'ATP total. Les altérations mitochondriales observées chez les souris Acox1-/- sont en grande partie corrigées par l'expression de l'ACOX1 humaine. Ceci montre le rôle indispensable de l'ACOX1 dans l'homéostasie de la fonction mitochondriale.L'ensemble des résultats obtenus au cours de ce travail confirme l'importance de l'activité acyl-CoA oxydase 1 pour la dégradation des AGTLC au niveau du système de β-oxydation peroxysomale et pour la biogenèse du peroxysome. L'accumulation des substrats non métabolisés en absence d'ACOX1 pourrait être à l'origine de la perturbation de la fonction mitochondriale montrant à quel point l'activité de l'ACOX1 est indispensable au métabolisme cellulaire
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Van, der Linde Wilhelmina Johanna. "The metabolic profile of phenylbutyric acid and its antioxidant capacity in vervet monkeys / Wilhelmina Johanna van der Linde". Thesis, North-West University, 2010. http://hdl.handle.net/10394/4916.
Testo completoAbstract (sommario):
X–linked adrenoleukodystrophy (X–ALD) is the most common peroxisomal enzyme deficiency disorder, characterized by inborn mutations in the ABCD1 gene, an ATP–binding cassette (ABC) half–transporter. The ABCD1 gene encodes the adrenoleukodystrophy protein (ALDP), the transporter for the very–long–chain fatty acids (VLCFA; C > 22:0) from the cytosol into the peroxisomes to enter the peroxisomal B–oxidation pathway. The diagnostic disease marker is the elevated levels of VLCFAs which accumulate in different tissues and body fluids, leading to inflammatory demyelination, neuro–deterioration and adrenocortical insufficiency. At present, there is no satisfactory therapy for X–ALD available. However, another peroxisomal ABC half–transporter, ALDRP can compensate for the functional loss of ALDP and is encoded by the ABCD2 gene. This prompted a new approach to treatment strategies. Phenylbutyric acid (PBA) over–expresses the ABCD2 gene, leading to an increased expression of ALDRP and PBA decreases VLCFA levels by increasing peroxisomal B–oxidation. This study had a dual aim: to determine the antioxidant capacity of PBA and to verify known and identify new metabolites of PBA. In vitro, HeLa cells were cultivated and treated with 0.5 mM, 1 mM, 2 mM and 5 mM PBA for 48 hours. The ROS, lipid peroxidation, apoptosis and cell viability were determined using fluorescein–based flow cytometry. Images were taken to visualize the peroxisome proliferation. In vivo, a vervet monkey was given a single dose of 130 mg/kg PBA. Blood was collected before treatment and 15 minutes, 30 minutes, 1, 2 and 3 hours after treatment. ROS, apoptosis and lipid peroxidation were determined by fluorescein–based flow cytometry. Urine was collected before treatment and 15 minutes, 30 minutes, 1, 2, 3, 7 and 24 hours after PBA treatment. A standardised method, employing gas chromatography–mass spectrometry (GC/MS), was used to analyse the organic acids in the urine and fatty acids in the blood. In vitro results showed decreased levels of ROS and lipid peroxidation with increased concentrations of PBA. PBA showed a protective effect towards the HeLa cells with reduced apoptosis and a high number of viable cells. In vivo levels of ROS en lipid peroxidation decreased over time of treatment with PBA. The fluorescence microscope images confirmed an increased number of peroxisomes after PBA treatment. The short term effect of PBA showed an initial, but small decrease in the levels of the fatty acids, suggesting induction over a longer period rather than activation of peroxisomal B–oxidation. New metabolites of phenylbutyrate were identified in the urine of a vervet monkey. These new metabolites originated from monooxygenase, N–phenylacetyl–glutamine synthases and B–oxidation byproducts. Recently discovered metabolites in humans and rats were also verified and confirmed in the vervet monkey. We therefore propose that treatment with PBA, on account of its beneficial effects of restoring VLCFA levels and reducing oxidative stress, could be considered a novel approach for the treatment of X–ALD.Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2011.
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Rosa, Ricardo Manuel Balixa da. "Unravel the functions of Acbd5 through the generation and characterization of mouse mutants". Master's thesis, 2019. http://hdl.handle.net/1822/65492.
Testo completoAbstract (sommario):
Dissertação de mestardo em Applied Biochemistry Specialization (área de especialização em Biomedicine)Lipids are the major class of macromolecules present in the brain, so mutations in proteins that are somehow related with lipid metabolism may cause several disorders in the nervous system. Peroxisome is one vital organelle in lipid metabolism, catalyzing anabolic and catabolic processes, such as fatty acid oxidation and plasmalogen biosynthesis, crucial for myelination. Acyl-CoA binding domain 5 (ACBD5) is a peroxisomal membranar protein implicated in the internalization of very long chain fatty acids (VLCFA) into the peroxisome. Mutations in ACBD5 can lead to VLCFA accumulation and decreased levels of plasmalogens, leading to neurological pathologies, such as retinal dystrophy, leukodystrophy and spastic paraparesis in humans. Mouse models conjugated with CRISPR-Cas9 technique were used to obtain several mutant mice with unique defects in Acba 5. Our objective was focused in the understanding of how ACBD5 deficiencies impact tissue pathology and the underlying mechanism, applying some strategies, such as, immunofluorescence, transmission electron microscopy and western blots. The Gly357* mutant developed a spinocerebellar ataxia, and displayed phenotypic irregularities, such as, failure to thrive, kyphosis, tremors, hindlimb and forelimb clasping and coordination problems. At a pathological level, several abnormalities appear in different tissues: lipid accumulation in liver, Purkinje cell (PC) loss in the cerebellum and giant axonopathy and signs of hypomyelination in spinal cord with organelle accumulations and disorganized cytoskeleton within the axon. Western blot analysis was performed for myelin proteins, which seemed to be decreased in spinal cord and also for tubulin post-translational modifications like acetylation and for A2-tubulin, that were significantly increased and decreased, respectively. Despite these findings, more research need to be performed preferentially at molecular level to unravel the mechanisms behind such a pathofisiology, making possible the discovery of a therapeutic pathway.
Os lípidos constituem a maior classe de macromoléculas no cérebro, por isso, mutações que ocorram em proteínas que estejam de certa forma envolvidas com o metabolismo lipídico podem ser causadoras de várias patologias relacionadas com o sistema nervoso. O peroxissoma é um organelo vital para o metabolismo lipídico, tendo tanto processos anabólicos como catabólicos, como a oxidação de ácidos gordos e a biossíntese de plasmalogénios, cruciais para a mielinização. "Acyl-CoA binding domain 5" (ACBD5) é uma proteína peroxissomal transmembranar implicada na internalização dos ácidos gordos de cadeia muito longa para dentro do peroxissoma. Mutações no gene ACBD5 podem levar a acumulações de ácidos gordos de cadeia muito longa e a diminuições nos níveis de plasmalogénios, provocando patologias a nível neurológico, como distrofia da retina, leucodistrofia e paraparésia espástica em humanos. Modelos animais em murganhos, conjugados com a técnica de CRISPR-Cas9 foram usados para obter os primeiros ratinhos mutantes com defeitos únicos no gene Acba5. O nosso objetivo esteve focado na compreensão de como deficiências na ACBD5 têm impacto na patologia dos tecidos e os seus mecanismos subjacentes. O mutante Gly357* desenvolve uma ataxia espinocerebelar, a qual apresenta irregularidades fenotípicas, como a incapacidade de ganhar peso, cifose, tremores, e problemas de coordenação motora. Ao nível patológico várias alterações são evidentes em diferentes tecidos: a acumulação lipídica no fígado, perda de células Purkinje no cerebelo e uma grande axonopatia e sinais de hipomielinização na espinhal medula, com acumulação de organelos e desorganização do citoesqueleto no interior do axónio. Foi também observada um astrocitose generalizada no cérebro, espinhal medula e cerebelo. Também foram realizados "western blots" para proteínas da mielina, as quais parecem estar reduzidas na espinhal medula e também para modificações pós-traducionais da tubulina como acetilação e tubulina A2, que estavam aumentadas e diminuidas, respetivamente. Apesar destas descobertas, mais pesquisa precisa de ser feita, preferencialmente a nível molecular, de forma a desvendar quais os mecanismos por detrás desta patofisiologia, possibilitando a descoberta de uma via terapêutica.
Libri sul tema "VLFCA"
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van Geel, Björn M., Marc Engelen e Stephan Kemp. X-linked Adrenoleukodystrophy. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199972135.003.0061.
Testo completoAbstract (sommario):
X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disorder. Hallmarks are increased levels of plasma very long-chain fatty acids (VLCFA), mutations in the ABCD1 gene, impaired function of ALD-protein and, consequently, decreased import of VLCFA-CoA esters in peroxisomes and VLCFA beta-oxidation. Cerebral demyelination and axonal degeneration of the spinal cord are the main causes of neurological deficits. Endocrine dysfunction, particularly adrenocortical insufficiency, is very frequent. Based upon the age of onset of symptoms and the organs most severely affected, several phenotypes can be distinguished. Adrenomyeloneuropathy (AMN) and childhood cerebral adrenoleukodystrophy (CCALD) are the most frequent variants. At least 80% of female carriers will eventually develop neurological symptoms similar to men with AMN. The thin and scanty scalp hair in affected men may facilitate diagnosis of X-ALD. Identification of patients is of utmost importance, as adrenocortical insufficiency can be treated, rapidly progressive cerebral demyelination can be halted, and prenatal diagnostic testing is available. Furthermore, symptomatic therapies and multidisciplinary support may help patients coping with this disease.
2
Vaz, Frédéric M., e Ronald J. A. Wanders. Interpretation of Very-Long-Chain Fatty Acids Analysis Results. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199972135.003.0086.
Testo completoAbstract (sommario):
The analysis of very long-chain fatty acids (VLCFAs) is a crucial step in the diagnostic work-up of patients suspected to suffer from a peroxisomal disorder (PD) including X-linked adrenoleukodystrophy (X-ALD). Although different analytical procedures have been described for the analysis of VLCFAs, most laboratories use GC/MS-analysis as method of choice. As described below, VLCFA-analysis is a robust and reliable diagnostic method which is usually unequivocal except in rare cases.
Capitoli di libri sul tema "VLFCA"
1
Claude, Cassagne, Bessoule Jean-Jacques, Schneider Florence, Lessire René, Sturbois Bénédicte, Moreau Patrick e Spinner Christel. "Modulation of the Very-Long-Chain Fatty Acid (VLCFA) Formation in Leek". In Plant Lipid Metabolism, 111–14. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-015-8394-7_32.
Testo completo
2
"VLCFA". In Springer Reference Medizin, 2481. Berlin, Heidelberg: Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-48986-4_301707.
Testo completo
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Wierzbicki, Anthony S. "Disorders of peroxisomal metabolism in adults". In Oxford Textbook of Medicine, 1719–29. Oxford University Press, 2010. http://dx.doi.org/10.1093/med/9780199204854.003.1209_update_002.
Testo completoAbstract (sommario):
The peroxisome is a specialized organelle which employs molecular oxygen in the oxidation of complex organic molecules including lipids. Enzymatic pathways for the metabolism of fatty acids, including very long-chain fatty acids (VLCFA) enable this organelle to carry out β-oxidation in partnership with mitochondria. A peroxisomal pathway for isoprenoid lipids derived from chlorophyll, such as phytanic acid, utilizes ...
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Mendell, Jerry R. "Peroxisomal Defects: Refsum Disease and Adrenomyeloneuropathy". In Diagnosis and Management of Peripheral Nerve Disorders, 492–507. Oxford University PressNew York, NY, 2001. http://dx.doi.org/10.1093/oso/9780195133011.003.0024.
Testo completoAbstract (sommario):
Abstract Peroxisomes are single-membrane-bound organelles, measuring about 0.2 to 0.5 µm in diameter. They lack DNA and have no defined internal cytoarchitecture. These organelles are found in all cells in the human body, especially the liver and kidney, but are absent from mature erythrocytes.1 Peroxisomes catalyze the 13 oxidation of fatty acids and related substrates. Those preferentially or exclusively oxidized in peroxisomes include very long chain fatty acids (VLCFA), polyunsaturated fatty acids, dicarboxylic fatty acids, prostaglandins, and the side chain of cholesterol. Peroxisomes also catalyze the initial reaction in the biosynthesis of plasmalogens, which are phospholipids abundantly found in the myelin. Bile acid formation requires peroxisomes and they are the principal site for H202-based cellular respiration using catalase and oxidases. Peroxisomal disorders can be divided into two major categories: those in which peroxisomes are absent or severely reduced because their assembly is defective, and disorders involving single peroxisomal enzyme defects. The peroxisomal disorders associated with neurological dysfunction are listed in Table 24-1. Peripheral neuropathy occurs as a predominant manifestation of two peroxisomal disorders, both caused by single enzyme defects: Refsum disease (Table 24-2) and X-linked adrenomyeloneuropathy (a subtype of adrenoleukodystrophy) (see Table 24-3). These disorders are genetically distinct from other conditions that carry similar names: neonatal adrenoleukodystrophy and infantile Refsum disease.
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Moser, Hugo, e Nga Hong Brereton. "Adrenoleukodystrophy And Other Peroxisomal Disorders". In Pediatric Nutrition In Chronic Diseases And Developmental Disorders, 312–17. Oxford University PressNew York, NY, 2005. http://dx.doi.org/10.1093/oso/9780195165647.003.0045.
Testo completoAbstract (sommario):
Abstract Genetically determined peroxisomal disorders are divided into two major categories: (1) disorders of peroxisome biogenesis, in which the organelle is not normally formed, and (2) disorders that involve a single peroxisomal enzyme. The biochemical and gene defects in each of these disorders have been defined. A list of the disorders with pertinent references follows: X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. Its frequency is estimated to be 1:17,000 and approaches that of phenylketonuria. The gene defect involves ABCD1, a gene that has been mapped to chromosome Xq28 and codes for a peroxisomal membrane protein, ALDP. The principal biochemical abnormality is the accumulation of saturated very long chain fatty acids (VLCFA), mainly hexacosanoic (C26:0) and tetracosanoic (C24:0), in tissues and also in plasma. X-linked adrenoleukodystrophy leads to progressive neurological disability. Approximately 70% of patients also have adrenal insufficiency (Addison disease), which responds well to adrenal hormone replacement therapy. X-linked adrenoleukodystrophy involves the X chromosome. Men, who have only one X chromosome, are thus more severely affected. Women, who have one abnormal X chromosome, are referred to as heterozygotes and are protected to a varying extent by their other X chromosome, which is nearly always normal. Early neurological and mental development is entirely normal in both boys and girls.
Atti di convegni sul tema "VLFCA"
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Van Duong, Binh, An Trong Nguyen, Chien Nhu Ha, Hong-Hanh Thi Duong, My-Linh Thi Tran e Trong-Hop Do. "UIT-VLFC: Vietnamese Lipstick Feedbacks Corpus". In 2022 25th Conference of the Oriental COCOSDA International Committee for the Co-ordination and Standardisation of Speech Databases and Assessment Techniques (O-COCOSDA). IEEE, 2022. http://dx.doi.org/10.1109/o-cocosda202257103.2022.9997964.
Testo completo
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Vasconcelos, Matheus Felipe de Souza, Francisco Tomaz Meneses de Oliveira, Rafael Zini Moreira da Silva e Alex Michel Daoud. "Neurological and adrenal insufficiency symptons in adult x-linked adrenoleukodystrophy: case report". In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.347.
Testo completoAbstract (sommario):
Context: X-linked adrenoleukodystrophy (X-ALD) is a rare genetic demyelinating disease caused by mutations in ABC1 gen associated with an impairment of beta- oxidation of very long chain fatty acids (VLCFA) in peroxisomes. It causes accumulation of VCLFA in tissues affecting majoritary the central nervous system, testicles and the adrenal córtex resulting in symptoms which provides restricted neurological prognosis and sequels. Methods: Specific data related of a clinical case through prontuary and complementary exams in a patient attended at Santa Casa de Misericórdia de São Paulo hospital. Case report: Male patient, 39 years old, complaning about vomiting, hyperpigmented skin associated with abolish, psicoses, urinary incontinence, temporal and spacial confusion as well as were found: hyperkalaemia, hyponatremia, hypoglycemia, elevated ACTH levels, basal cortisol decresead, antibody anti-21-hidroxilase non reagente, screening for infectious agents were carried out and infection subsequently ruled out. Were observed in MRI Brain: hypersignal in cerebral white matter on T2-FLAIR sequence bilaterally in which the occipitoparietal region, frontal lobe and basal ganglia were more affected. After metabolic and hydroelectric disorders estabilization using Prednisone, Fludrocortisone per day for 5 days, he evolved with worsening of cognitive and behavioral status until nowdays. Actually, he is totally dependent on his basic activities. Conclusions: It is a rare disease, but it must be recognized by every neurologist, since it is can affect other systems and can leave serious sequelae.