The objective of the research was to investigate proton-coupled electron transfer (PCET) reactions involving antioxidants to gain insight into the detailed mechanisms of glutathione (GSH), Trolox, and α-tocopherol (α-TOH). PCET reactions are complex redox reactions that transfer electrons and protons sequentially or in concert. These reactions are ubiquitous in natural or artificial processes that produce electrochemical energy that is extractable as electricity or as chemical fuels of high energy content. Examples of processes based on PCET are photosynthesis, respiration, nitrogen fixation, carbon dioxide reduction, redox fuel cells, and artificial photosynthesis. Antioxidants were selected as a PCET model to understand the coupling between proton transfer (PT) and electron transfer (ET) in order to elucidate structure-reactivity relationships under different experimental conditions. PCET reactions were studied with a set of electrochemical techniques to propose a preliminary mechanism that could be validated with digital simulations matching the electrochemical response. In some cases, other analytical techniques were used to aid in the system characterization. This thesis presents the results and discussion of the effects of oxidant-base pairs on the mediated oxidation of GSH, the -2e-/-H+ process of Trolox in aqueous and nonaqueous solvents with various pH values, and the particle collision electrolysis of α-tocopherol in oil-in-water emulsion droplets on an ultramicroelectrode. Ultimately our goal was to determine the kinetic and thermodynamic factors that control PCET reactions so that they can be applied in designing artificial systems for the production of energy using more abundant reagents with lower cost and better yields.

Les matériaux susceptibles de couvrir les besoins technologiques dans le domaine de l'émission Laser infrarouge pour des applications entre 3 µm et 12 µm, et qui engloberait les trois fenêtres de transparence de l'atmosphère sont peu nombreux. Les iodates métalliques s'avèrent être des composés potentiels. En effet il a été montré que les composés étudiés présentent les caractéristiques communes suivantes : bonne stabilité thermique, non hygroscopicité, fenêtre de transparence sur poudre qui s'étend du visible au début de l'infrarouge lointain (12 µm), seuil de dommage optique sur poudre de l'ordre de quelques GW.cm-2. Le travail présenté dans cette thèse porte essentiellement sur la synthèse et la détermination structurale de nouveaux composés iodates non-centrosymétriques en vue de les doper avec des ions terres rares ou métaux de transition luminescents afin d'obtenir des matériaux bifonctionnels qui peuvent être à la fois luminescents pour générer la source de lumière Laser et non linéaire pour convertir la fréquence de l'émission initiale. La matrice non-centrosymétrique AgGd(IO3)4 a pu être dopée avec des ions Nd3+ et Yb3+, présentant des durées de vie de luminescence du même ordre de grandeur que celui de certains lasers commerciaux. L'étude sur les iodates de lanthane a permis la caractérisation de La(IO3)3(HIO3) et La(IO3)3(HIO3)1,33 obtenus par cristallisation lente dans une solution aqueuse d'acide nitrique, alors que le composé anhydre α-La(IO3)3 est obtenu par synthèse hydrothermale. Ce dernier est un candidat potentiel en tant que matrice laser par l'insertion d'ions lanthanides.

Ischemic brain injury causes neurodegeneration. In this study, the mechanism of neurodegeneration was investigated by examining the role of sterol regulatory element binding protein-1 (SREBP-1), CCAAT enhancer binding protein&amp / #946 / (C/EBP&amp / #946 / ), glutathione (GSH), malondialdehyde (MDA), glutathione-S-transferase (GST), and superoxide dismutase (SOD). Carotid artery occlusion (CAO) plus hypotension was produced for 10 minutes. Control groups were sham operated. Animals were sacrificed after 24 hours, 1 week, 2 and 4 weeks of reperfusion periods. The expression of C/EBP&amp / #946 / and SREBP-1 in rat brain cortex and cerebellum were examined by western blotting. C/EBP&amp / #946 / expressions significantly increased in both cytosolic (1.19, 1.58 fold) and nuclear (1.73, 1.81 fold) extracts of brain cortex at 24 hours and 1 week CAO groups, respectively. In cerebellum, C/EBP&amp / #946 / expression significantly increased in 1 week, cytosolic (1.63 fold), and nuclear (1.35 fold) extracts. SREBP-1 expression increased significantly in both cytosolic (2.07 fold) and nuclear (1.41 fold) extracts of brain cortex in 1 week. SREBP-1 expression significantly increased in cytosolic (2.15 fold) and nuclear (1.79 fold) extracts of cerebellum in 1 week. There were no significant alterations in SREBP-1 C/EBP&amp / #946 / expressions for 2 and 4 weeks in both cytosolic and nuclear extracts of brain cortex and cerebellum. There were insignificant changes in GSH and GST levels in cortex. However, MDA and SOD levels significantly increased by 43.0 % and 47.3 %, respectively, in 24 hours. Our findings indicate that increase in SREBP-1 and C/EBP&amp / #946 / expressions may be related to oxidative stress during ischemic neurodegenerative processes.

Thesis (PhD) -- Macquarie University, Division of Environmental and Life Sciences, Dept. of Chemistry and Biomolecular Sciences, 2007. / Bibliography: leaves 295-322. / Generation of peroxide groups in proteins exposed to a wide variety of reactive oxygen species (ROS) requires an initial formation of protein carbon-centred or peroxyl free radicals, which can be reduced to hydroperoxides. Both protein radicals and protein hydroperoxides are capable of oxidizing important biomolecules and thus initiate biological damage. In this study, we investigated the inhibition of protein hydroperoxide formation by ascorbate and GSH in gamma-irradiated HL-60 cells.--We used HL-60 cells as a model for general protection of living organisms by ascorbate (Asc) and glutathione (GSH) from the deleterious effects of protein hydroperoxides generated by radicals produced by gamma radiation. Measurement by HPLC indicated that incubation of HL-60 cells with Asc in the presence of ascorbate oxidase resulted in the accumulation of intracellular Asc. The intracellular Asc levels were lowered by irradiation, demonstrating intracellular consumption of Asc by the radiation-generated radicals. Exposure of HL-60 cells to increasing gamma irradiation doses resulted in increasing accumulation of protein peroxides in the cells. This was measured by the FOX assay. A significant decrease in intracellular protein hydroperoxides was noted when the cells were treated with ascorbic acid before irradiation. A dose-dependent protective effect of Asc was observed. Asc loading also provided strong protection from radiation-generated protein hydroperoxides independently of the composition of the external medium, showing that only the radicals formed within the cells were effective in oxidizing the cell proteins. Similarly, protein peroxidation was inhibited in cells with enhanced levels of GSH and increased when the intracellular GSH concentration was reduced. These findings indicate that ascorbate and GSH are important antioxidants in protecting cells from oxidative stress associated with the generation of protein hydroperoxide. / Mode of access: World Wide Web. / xxix, 322 leaves ill

Le travail présenté dans ce mémoire de thèse avait pour but de synthétiser de nouveaux composés pour des applications en imagerie médicale. La première partie porte sur la synthèse de ligands hétéroleptiques pour la chélation de deux métaux différents en vue d’une utilisation dans deux types d’imagerie. Pour cela, nous avons d’abord synthétisé des porphyrines. Ces molécules sont connues pour la chélation de nombreux métaux de transition et notamment le cuivre, dont l’isotope cuivre-64 est un radioémetteur β+ utilisable en Tomographie par Émission de Positron (TEP). Ces porphyrines ont été couplées à un dérivé du DOTA, molécule connue pour son application, après métallation avec du gadolinium, en Imagerie par Résonance Magnétique (IRM). Ces composés possèdent des valeurs de relaxivité encourageantes pour une application en IRM. Enfin, des biomolécules ont été modifiées afin de vectoriser nos composés. La seconde partie porte sur la synthèse de composés pour l’imagerie médicale par optique non-linéaire. Nous avons dans un premier temps synthétisé des porphyrines amphiphiles et zwiterrioniques pour la Génération de Second Harmonique (GSH). Leur efficacité a été mesurée et celle-ci est suffisante pour pouvoir envisager l’obtention d’images. Dans un second temps, nous avons travaillé sur la synthèse d’un composé pour une application en imagerie biphotonique et en IRM. Pour cela, nous avons relié un dérivé du DOTA avec un fluorophore de type DPP. Le composé final a été métallé avec du gadolinium et sa relaxivité est supérieure à celle du DOTA(Gd). / The goal of my PhD studies was to synthesize new compounds for possible medical imaging applications. The first part of my thesis focused on the synthesis of heteroleptic ligands to achieve the chelation of two different metals aimed at addressing two types of medical imaging. We first synthesized porphyrins, which are well-known for the chelation of numerous transition metals. We focused on copper, whose copper-64 isotope is a β+ emitter usable in Positron Emission Tomography (PET). These porphyrins have been coupled with a DOTA derivative. This molecule, metallated with gadolinium, is well-known in Magnetic Resonance Imaging (MRI). Our compounds display encouraging relaxivities for MRI applications. At last, these molecular probes have been conjugated to a few biomolecules in order to vectorize our compounds. The second part of this work is related to the synthesis of fluorophores for nonlinear optical imaging. We first synthesized amphiphilic zwitterionic porphyrins for Second Harmonic Generation (SHG). The efficiency of these compounds has been measured and was satisying enough to consider the possibility to perform imaging studies. We also worked on the synthesis of compounds for Two Photon Emission Fluorescence (TPEF) imaging and MRI. We have linked a DOTA derivative with a diketopyrrolopyrrole (DPP). This conjugate has been metallated with gadolinium and its relaxivity has been measured. Interestingly, this value is superior to that of DOTA(Gd).

Autism is a lifelong neurodevelopmental disorder. The etiology of autism still remains unclear due to the heterogeneous and complex nature of the disorder, however synergistic actions between genetic components and environmental factors have been suggested. Acetaminophen (APAP) is one of the most popular over-the-counter drugs that possess antipyretic and analgesic effects. It is considered a relatively safe and effective within therapeutic doses. Recently, early exposure to APAP has been suggested to be one of the underlying cause of autism. Children are often prescribed APAP to lessen fever or irritability after vaccination during the first year, and APAP may adversely affect the normal brain development. In order to better understand the association with APAP and autism, we used an inbred mouse strain BTBR T+tf/J (BTBR). BTBR exhibits behavioral deficits that mimic the core behavioral deficits of human autism. In the study, investigated 1) if BTBR mice showed differences in thiol biochemistry and EAAT3 levels in brain compared with C57BL/6J (C57) mice, 2) if early exposure to APAP induced behavioral changes worsening the autistic phenotypes of BTBR in adolescence, and 3) if APAP exposure in neonatal mice induced possible toxicity at various doses. As a result, we observed that BTBR mice have significantly lower plasma sulfate levels and EAAT expression levels in the frontal cortex compared to C57 mice. Surprisingly, neonatal therapeutic dose of APAP administration did not induce behavioral changes in both C57 and BTBR in adolescence. However, we showed that a supratheraputic dose of APAP significantly elevated levels of oxidative stress marker in the brain. Overall, the results suggested that BTBR mice would be a useful mouse model to investigate effects of various environmental factors that have been associated with autism. In addition, early exposure to APAP at supratherapeutic doses may negatively affect normal brain development.

Soils in many regions in North America, including Quebec, are selenium (Se) deficient. To date, no field study has been conducted in Quebec regarding the Se status of horses. The objectives of this study were (1) to measure plasma Se in horses from different geographical locations in the province of Quebec and (2) to survey the Se consumption of the sampled horses. Four samplings were done on 59 horses over a 1-year period. Plasma was analyzed for Se, vitamin E and GSH-Px. Hay, concentrate and water were also analyzed for Se. Horses were classified in four groups for statistical analysis according to their forage:concentrate consumption respectively: group 1- 100% : 0%; group 2- 75-99% : 1-24%; group 3- 51-74% : 25-49%; group 4- < 50% : ≥ 50%. Owners were asked questions from a survey questionnaire at each visit. Results demonstrate that plasma Se varies according to BCS (P = 0.031) (n = 224 measures, 1 measure/horse/season), the season (P = 0.015) and the feeding group (P< 0.001). Plasma vitamin E was affected by the sex (P = 0.047) (mares: n = 37, geldings: n = 18, stallions: n = 4), the exercise level (P< 0.001) and the season (P< 0.001). GSH-Px activity was influenced by the type of feeding only (P = 0.002). When comparing plasma Se, vitamin E and GSH-Px results along with the answers of the survey questionnaire, it is possible to conclude that feeding practices of horse owners in Quebec are not appropriate to meet the Se requirements of horses. / Les sols de plusieurs régions en Amérique du Nord, incluant le Québec, sont déficients en sélénium (Se). À ce jour, aucune étude sur le terrain n’a été menée au Québec en ce qui concerne le statut en Se des chevaux. Les objectifs de cette étude étaient (1) de mesurer le Se sanguin chez des chevaux de différentes régions du Québec et (2) de recenser la consommation de Se des chevaux échantillonnés. Quatre échantillonnages ont été réalisés sur 59 chevaux durant une période d’un an. Le plasma a été analysé pour les éléments suivants : le Se, la vitamine E (interagit avec le Se en tant qu’antioxydant) et la glutathion peroxydase (GSH-Px). Le foin, les concentrés et l’eau consommés pas les chevaux ont aussi été analysés pour le Se. Les chevaux étaient classés en quatre groupes en raison de leur consommation de fourrages:concentré respectivement : groupe 1 - 100% : 0%; groupe 2- 75-99% : 1-24%; groupe 3- 51-74% : 25-49%; groupe 4- < 50% : ≥ 50%. Les propriétaires ont été sondés à chaque visite en utilisant un questionnaire validé. Les résultats démontrent que le niveau de Se plasmatique varie en fonction de l’état de chair (P = 0.031) (n = 224 mesures, 1 mesure/cheval/saison), de la saison (P = 0.015) et du groupe alimentaire (P< 0.001). La vitamine E plasmatique était influencée par le sexe (P = 0.047) (juments : n = 73, hongres : n = 18, étalons : n = 4), le niveau d’exercice (P< 0.001), et par la saison (P< 0.001). L’activité de la GSH-Px variait en fonction du groupe alimentaire (P = 0.002). À partir des résultats sanguins et des réponses au questionnaire, il est possible de conclure que les pratiques alimentaires des propriétaires de chevaux du Québec ne sont pas appropriées afin de répondre aux besoins en Se des chevaux.

INTRODUÇÃO: Metionina (Met), cisteína (Cys), homocisteína (Hcy) e taurina (Tau) são os quatro aminoácidos sulfurados (AAS), mas apenas a Met e Cys são incorporadas em proteínas. Os três principais produtos doS AAS, glutationa, (GSH), Hcy e Tau influenciam, principalmente, as respostas inflamatória e imune. A Tau e GSH diminuem a inflamação, enquanto que a Hcy apresenta efeito oposto. Os pacientes HIV+ apresentam baixos níveis de GSH e outros nutrientes antioxidantes, mostrando relação direta entre Cys (e GSH) com células CD4+. Não se conhece o mecanismo pelo qual as mudanças na ingestão dos AAS influenciam este fenômeno. Paralelamente, as relações entre Hcy, doenças inflamatórias e alterações in vitro no comportamento das células imunes levantou ressalvas sobre a suplementação de dietas com AAS. OBJETIVOS : investigar as vias dos AAS em pacientes HIV+ nas condições de jejum e pós-sobrecarga de Met frente à dieta habitual (OH) isolada ou acompanhada da suplementação de Cys (NAC) ou glutamina (Gln). MÉTODOS : 12 pacientes HIV+ (6 M e 6 F, de 25 a 36 anos), sob tratamento anti-retroviral pelo esquema tríplice, sem infecções secundárias e 20 controles saudáveis (10M e 10F, 23-28 anos) foram randomicamente distribuídos para suplementação com NAC (N-acetilcisteína, 1g/d) ou Gln (20 g/d) em estudo cruzado com 7 dias de dieta separados por uma semana de washout (Wo com DH). Amostras de sangue após jejum noturno de 10 a 12 horas foram coletadas antes (MO) e após (M1) cada regime dietético. A seguir, os indivíduos ingeriram metionina (100 mg/kg), com coletas de sangue após 2 e 4 horas para a determinação da área abaixo da curva (AAC). No MO, ambos os grupos foram avaliados quanto à antropometria (IMC, kg/m2), funções glomerular (uréia, creatinina) e hepatocelular (&#947;-GT), estados nutricional (albumina, cálcio, ácido fólico e vitamina 812) e antioxidante (ácido úrico, GSH, GSSG, Hcy), glicose, lipídios (triacilgliceróis e frações de colesterol) e AAS, serina (Ser), glicina (Gly), glutamato (Glu) e Gln. O grupo HIV também foi caracterizado pela carga viral e contagem de CD4+ e CD8+. As comparações estatísticas entre os grupos e entre as dietas mostraram homogeneidade para IMC, albumina, cálcio, vitamina 812, Hcy, HDL-colesterol, uréia e creatinina. Os pacientes apresentaram valores maiores de glicose, triacilgliceróis, &#947;-GT, LDL-colesterol e GSSG paralelalemente às menores concentrações de ácido úrico, GSH e todos os AAS, exceto Hcy. A sobrecarga de metionina igualou (pelos valores de delta) os grupos para Met, Hcy, Tau e Gln. As suplementações de NAC e Gln levaram o grupo HIV+ a concentrações maiores de GSH (NAC > Gln), atuando diferentemente em seus precursores: G/y (Gln > NAC) e Cys (NAC > Gln) e resultando em consumo similar de Ser e produção de Tau. Ambas as dietas reduziram GSSG/GSH (NAC > Gln) e apenas NAC aumentou (6 x) a Hcy. Esta última foi piorada pela sobrecarga de Mel. Assim, HIV+ resulta em deficiências múltiplas de vitaminas e aminoácidos levando a menores níveis de GSH e GSSG/GSH mais elevada. Os principais problemas de menor formação de Cys e menor incorporação de Cys em GSH foram resolvidos dando-se Met, NAC e Gln aos pacientes, ainda permanecendo a desvantagem do aumento da Hcy com Met ou suplementação de NAC. / BACKGROUNO: Methionine (Met), cysteine (Cys), homocysteine (Hcy), and, taurine (Tau) are the 4 sulfur-containing amino acids (SAA), but only Met and Cys are incorporated into proteins. The 3 major products of SAA, glutathione (GSH), Hcy and Tau influence, mainly, inflammatory and of immune responses. Tau and GSH ameliorate inflammation whereas Hcy has the opposite effect. HIV+ patients present low levelis of GSH and other antioxidants nutrients, showing a direct relationship between Cys (and GSH) with CD4+/ cells. How changes in SAA intake influence this phenomenon is unknown and the relationships among Hcy, inflammatory diseases, and in vitro alterations in immune cell behavior create a cautionary note about supplementation of diets with SAA. OBJECTIVE: To investigate SAA pathways in HIV+ patients on fast and Met-overload (Met-DL) states after taken diet habitual without (HD) or with supplements of Cys (NAC) or glutamine (Gln). METHOOS: 12 HIV+ (6M and 6F, 25-36 yrs old) patients under HAART without secondary infections and 20 healthy (10M and 10F, 23-28 yrs old) controls were randomly assigned to either NAC (N-acetylcysteine, 1g/d) or Gln (20g/d) diets, in a 7-day diet crossover design, separated by a 7-day washout (with HD) period. Blood samples were drawn after overnight fast before (MO) and after each dietary treatments (M1) for the resting measurements. Immediately after blood sampling ali subjects started the Met-DL by ingesting at once 100 mg Met/kg BW and having the blood draw after 2 and 4 hours for the area under the curve (AUC) determination. At MO both groups were assessed for anthropometry (BMI, kg/m2), glomerular (plasma urea and creatinina) and hepatocellular (plasma &#947;GT activity) funetions, nutritional (albumin, calcium, folic acid and vitamin B12) and antioxidant (uric acid, GSH, GSSG, Hey) states, glucose, lipids (triglycerides and cholesterol fractions) and SAA, serine (Ser), glyeine (Gly), glutamate (Glu) and Gln. The HIV+ group was characterized also by viral load, CD4+ and CD8+ counts. The statistical comparisons between groups and among diets showed group homogeneity for 8MI, albumin, calcium, vitamin B12, Hey, HDL-cholesterol, urea and creatinine. The patients presented higher values of glucose, triglycerides, &#947;-GT, LDL-cholesterol, and GSSG along with lower concentrations of uric acid, GSH and all but Hcy amino acids. The Met-OL equalized (&#916; values) the groups for Met, Hcy, Tau and Gln. NAC and Gln diets led the HIV+ group to a higher concentrations of GSH (NAC > Gln) by acting differently on its precursors: Gly (Gln > NAC) and Cys (NAC > Gln), resulting similar consumption of Ser and production of Tau. Both diets reduced GSSG/GSH (NAC > Gln) and only NAC increased (6 x) Hey. The later was worsened by Met-OL. Thus HIV+ results in multiple deficiencies of vitamins and amino acids leading to lower levels of GSH and higher GSSG/GSH ration. The main problems of lower formation of Cys and low ineorporation of Cys and Gly into GSH were greatly solved by giving Met, NAC and Gln to the patients, hence remaining the drawback of increasing Hcy with Met or NAC supplements.

Improvement in the in vitro oxidative folding of disulfide-containing proteins, such as extracellular and pharmaceutically important proteins, is required. Traditional folding methods using small molecule aliphatic thiol and disulfide, such as glutathione (GSH) and glutathione disulfide (GSSG) are slow and low yielding. Small molecule aromatic thiols and disulfides show great potentiality because aromatic thiols have low pKa values, close to the thiol pKa of protein disulfide isomerase (PDI), higher nucleophilicity and good leaving group ability. Our studies showed that thiols with a positively charged group, quaternary ammonium salts (QAS), are better than thiols with negatively charged groups such as phosphonic acid and sulfonic acid for the folding of bovine pancreatic trypsin inhibitor (BPTI). An enhanced folding rate of BPTI was observed when the protein was folded with a redox buffer composed of a QAS thiol and its corresponding disulfide. Quaternary ammonium salt (QAS) thiols and their corresponding disulfides with longer alkyl side chains were synthesized. These QAS thiols and their corresponding disulfides are promising small molecule thiols and disulfides to fold reduced BPTI efficiently because these thiols are more hydrophobic and can enter the core of the protein. Conformational changes of disulfide-containing proteins during oxidative folding influence the folding pathway greatly. We performed the folding of BPTI using targeted molecular dynamics (TMD) simulation and investigated conformational changes along with the folding pathway. Applying a bias force to all atoms versus to only alpha carbons and the sulfur of cysteines showed different folding pathways. The formation of kinetic traps N' and N* was not observed during our simulation applying a bias force to all atoms of the starting structure. The final native conformation was obtained once the correct antiparallel β-sheets and subsequent Cys14-Cys38 distance were decreased to a bond distance level. When bias force was applied to only alpha carbons and the sulfur of cysteines, the distance between Cys14-Cys38 increased and decreased multiple times, a structure similar to the confirmation of N*, NSH were formed and native protein was ultimately obtained. We concluded that there could be multiple pathways of conformational folding which influence oxidative folding.

INTRODUÇÃO: Metionina (Met), cisteína (Cys), homocisteína (Hcy) e taurina (Tau) são os quatro aminoácidos sulfurados (AAS), mas apenas a Met e Cys são incorporadas em proteínas. Os três principais produtos doS AAS, glutationa, (GSH), Hcy e Tau influenciam, principalmente, as respostas inflamatória e imune. A Tau e GSH diminuem a inflamação, enquanto que a Hcy apresenta efeito oposto. Os pacientes HIV+ apresentam baixos níveis de GSH e outros nutrientes antioxidantes, mostrando relação direta entre Cys (e GSH) com células CD4+. Não se conhece o mecanismo pelo qual as mudanças na ingestão dos AAS influenciam este fenômeno. Paralelamente, as relações entre Hcy, doenças inflamatórias e alterações in vitro no comportamento das células imunes levantou ressalvas sobre a suplementação de dietas com AAS. OBJETIVOS : investigar as vias dos AAS em pacientes HIV+ nas condições de jejum e pós-sobrecarga de Met frente à dieta habitual (OH) isolada ou acompanhada da suplementação de Cys (NAC) ou glutamina (Gln). MÉTODOS : 12 pacientes HIV+ (6 M e 6 F, de 25 a 36 anos), sob tratamento anti-retroviral pelo esquema tríplice, sem infecções secundárias e 20 controles saudáveis (10M e 10F, 23-28 anos) foram randomicamente distribuídos para suplementação com NAC (N-acetilcisteína, 1g/d) ou Gln (20 g/d) em estudo cruzado com 7 dias de dieta separados por uma semana de washout (Wo com DH). Amostras de sangue após jejum noturno de 10 a 12 horas foram coletadas antes (MO) e após (M1) cada regime dietético. A seguir, os indivíduos ingeriram metionina (100 mg/kg), com coletas de sangue após 2 e 4 horas para a determinação da área abaixo da curva (AAC). No MO, ambos os grupos foram avaliados quanto à antropometria (IMC, kg/m2), funções glomerular (uréia, creatinina) e hepatocelular (&#947;-GT), estados nutricional (albumina, cálcio, ácido fólico e vitamina 812) e antioxidante (ácido úrico, GSH, GSSG, Hcy), glicose, lipídios (triacilgliceróis e frações de colesterol) e AAS, serina (Ser), glicina (Gly), glutamato (Glu) e Gln. O grupo HIV também foi caracterizado pela carga viral e contagem de CD4+ e CD8+. As comparações estatísticas entre os grupos e entre as dietas mostraram homogeneidade para IMC, albumina, cálcio, vitamina 812, Hcy, HDL-colesterol, uréia e creatinina. Os pacientes apresentaram valores maiores de glicose, triacilgliceróis, &#947;-GT, LDL-colesterol e GSSG paralelalemente às menores concentrações de ácido úrico, GSH e todos os AAS, exceto Hcy. A sobrecarga de metionina igualou (pelos valores de delta) os grupos para Met, Hcy, Tau e Gln. As suplementações de NAC e Gln levaram o grupo HIV+ a concentrações maiores de GSH (NAC > Gln), atuando diferentemente em seus precursores: G/y (Gln > NAC) e Cys (NAC > Gln) e resultando em consumo similar de Ser e produção de Tau. Ambas as dietas reduziram GSSG/GSH (NAC > Gln) e apenas NAC aumentou (6 x) a Hcy. Esta última foi piorada pela sobrecarga de Mel. Assim, HIV+ resulta em deficiências múltiplas de vitaminas e aminoácidos levando a menores níveis de GSH e GSSG/GSH mais elevada. Os principais problemas de menor formação de Cys e menor incorporação de Cys em GSH foram resolvidos dando-se Met, NAC e Gln aos pacientes, ainda permanecendo a desvantagem do aumento da Hcy com Met ou suplementação de NAC. / BACKGROUNO: Methionine (Met), cysteine (Cys), homocysteine (Hcy), and, taurine (Tau) are the 4 sulfur-containing amino acids (SAA), but only Met and Cys are incorporated into proteins. The 3 major products of SAA, glutathione (GSH), Hcy and Tau influence, mainly, inflammatory and of immune responses. Tau and GSH ameliorate inflammation whereas Hcy has the opposite effect. HIV+ patients present low levelis of GSH and other antioxidants nutrients, showing a direct relationship between Cys (and GSH) with CD4+/ cells. How changes in SAA intake influence this phenomenon is unknown and the relationships among Hcy, inflammatory diseases, and in vitro alterations in immune cell behavior create a cautionary note about supplementation of diets with SAA. OBJECTIVE: To investigate SAA pathways in HIV+ patients on fast and Met-overload (Met-DL) states after taken diet habitual without (HD) or with supplements of Cys (NAC) or glutamine (Gln). METHOOS: 12 HIV+ (6M and 6F, 25-36 yrs old) patients under HAART without secondary infections and 20 healthy (10M and 10F, 23-28 yrs old) controls were randomly assigned to either NAC (N-acetylcysteine, 1g/d) or Gln (20g/d) diets, in a 7-day diet crossover design, separated by a 7-day washout (with HD) period. Blood samples were drawn after overnight fast before (MO) and after each dietary treatments (M1) for the resting measurements. Immediately after blood sampling ali subjects started the Met-DL by ingesting at once 100 mg Met/kg BW and having the blood draw after 2 and 4 hours for the area under the curve (AUC) determination. At MO both groups were assessed for anthropometry (BMI, kg/m2), glomerular (plasma urea and creatinina) and hepatocellular (plasma &#947;GT activity) funetions, nutritional (albumin, calcium, folic acid and vitamin B12) and antioxidant (uric acid, GSH, GSSG, Hey) states, glucose, lipids (triglycerides and cholesterol fractions) and SAA, serine (Ser), glyeine (Gly), glutamate (Glu) and Gln. The HIV+ group was characterized also by viral load, CD4+ and CD8+ counts. The statistical comparisons between groups and among diets showed group homogeneity for 8MI, albumin, calcium, vitamin B12, Hey, HDL-cholesterol, urea and creatinine. The patients presented higher values of glucose, triglycerides, &#947;-GT, LDL-cholesterol, and GSSG along with lower concentrations of uric acid, GSH and all but Hcy amino acids. The Met-OL equalized (&#916; values) the groups for Met, Hcy, Tau and Gln. NAC and Gln diets led the HIV+ group to a higher concentrations of GSH (NAC > Gln) by acting differently on its precursors: Gly (Gln > NAC) and Cys (NAC > Gln), resulting similar consumption of Ser and production of Tau. Both diets reduced GSSG/GSH (NAC > Gln) and only NAC increased (6 x) Hey. The later was worsened by Met-OL. Thus HIV+ results in multiple deficiencies of vitamins and amino acids leading to lower levels of GSH and higher GSSG/GSH ration. The main problems of lower formation of Cys and low ineorporation of Cys and Gly into GSH were greatly solved by giving Met, NAC and Gln to the patients, hence remaining the drawback of increasing Hcy with Met or NAC supplements.