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1.
Clin Psychol Psychother ; 30(5): 913-930, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36861498

RESUMO

INTRODUCTION: There is a direct association between patients with insecure attachment style (IAS), behavioural inhibition (BIS) and behavioural activation (BAS) motivational systems, and anorexia nervosa (AN). However, the possible direct relationships between these three variables have not been studied. OBJECTIVE: The main objective of this study is to analyse the relationship between these variables and propose a framework for analysing and understanding these relationships. METHODOLOGY: A systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, searching the following terms: 'anorexia', 'attachment' and those related to motivational systems. The final search was limited to publications in English dated between 2014-2022 for 'anorexia and attachment' and 2010-2022 for 'anorexia and BIS/BAS'. RESULTS: Of the 587 articles retrieved, 30 were included in this study for the textual data analysis of the relationship between anorexia and attachment (17), anorexia and motivational systems (10) and anorexia, attachment and motivational systems (3). An association between avoidant IAS, AN and hypersensitivity to punishment of the BIS was observed in the analysis. A relationship was also observed with hyperreinforcement sensitivity of the BAS. After reviewing the articles, a possible relationship between the three factors, along with other mediating factors, was found. DISCUSSION: AN is directly related to the avoidant IAS and to BIS. Similarly, bulimia nervosa (BN) was directly related with anxious IAS and BAS. However, contradictions were found in the BN-BAS relationship. This study proposes a framework for analysing and understanding these relationships.


Assuntos
Anorexia Nervosa , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Anorexia , Ansiedade
2.
Artigo em Inglês | MEDLINE | ID: mdl-35954601

RESUMO

The use of information and communication technologies in the health field is known as eHealth. Nowadays, the application of technological and digital tools for maintaining/improving physical and mental health is experiencing an exponential boom. These tools have been perceived as a powerful support for face-to-face therapies and lifestyle changes. Nevertheless, there is not enough scientific research that analyses the impact and consequences of eHealth interventions. More studies are needed to validate its application. Therefore, the aim of this study was to evaluate the impact of eHealth tools in a programme called ePSICONUT. This programme was created to promote healthy lifestyle habits in university students. The sample consisted of 16 university students from the Dominican Republic aged 18−24 years (x¯ = 20.69; s = 1.74). ePSICONUT was developed in 12 weeks and its impact was analyzed by comparing the initial and the final psychological and lifestyle tests results, which were completed online by the participants. Results reported that the professionally supervised use of eHealth tools was associated with better psychological well-being, lees anxiety and depression, and better lifestyle habits (such as diet quality), even in stressful and changing situations such as the COVID-19 pandemic circumstances. However, more studies are needed to validate and promote the use of eHealth-based intervention programmes.


Assuntos
COVID-19 , Telemedicina , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estilo de Vida Saudável , Humanos , Saúde Mental , Pandemias , Estudantes/psicologia , Telemedicina/métodos , Universidades
3.
Artigo em Inglês | MEDLINE | ID: mdl-34299960

RESUMO

Healthy lifestyles should be encouraged in the workplace through the occupational health teams of the companies. The objective of the present study was to evaluate the adherence to a lifestyle intervention carried out in university employees during the COVID-19 pandemic and its impact on health-related quality of life (HrQoL). A randomized controlled trial following the CONSORT guidelines was performed, consisting of three supervised interventions lasting for 18 weeks: an educational intervention on healthy habits, a nutritional intervention, and a telematic aerobic and strength exercise intervention. Lifestyle and HrQoL were analyzed six months post-intervention to assess adherence. Twenty-three middle-aged participants completed the study. The intervention group significantly improved their lifestyle according to the Health Promoting Lifestyle Profile II questionnaire, especially in the categories of Health Responsibility, Physical Activity, and Nutrition, with a large effect size. Sitting time was reduced by 2.5 h per day, with a moderate effect size. Regarding HrQoL, the intervention group showed a clinically significant improvement in the Physical Component Summary. Despite the lockdown and the mobility restrictions caused by the COVID-19 pandemic, this intervention performed on university employees achieved adherence to a healthier lifestyle and improved their HrQoL, which is of great clinical relevance.


Assuntos
COVID-19 , Pandemias , Controle de Doenças Transmissíveis , Exercício Físico , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Qualidade de Vida , SARS-CoV-2 , Universidades
4.
Artigo em Inglês | MEDLINE | ID: mdl-34831954

RESUMO

The World Health Organization's global action plan on workers' health establishes that occupational health services should carry out lifestyle interventions within the workplace, to prevent the development of non-communicable diseases. The objective of the study was to compare adherence to a healthy lifestyle six months after completion of a multi-component intervention with remotely supervised physical activity during the COVID-19 pandemic versus a multi-component intervention with in-person supervised physical exercise before the COVID-19 pandemic in university employees with unhealthy habits and predisposed to change. A prospective cohort study following the "Strengthening the Reporting of Observational studies in Epidemiology" (STROBE) guidelines was conducted, with two arms. Each multi-component intervention lasted for 18 weeks, and consisted of education on healthy habits, Mediterranean Diet (MedDiet)-based workshops, and a physical exercise program. Twenty-one middle-aged sedentary university employees with poor adherence to the MedDiet completed the study. Six months after completion of the intervention, both groups increased physical activity levels, adherence to the MedDiet, eating habits, health-promoting lifestyle, health responsibility, and health-related quality of life. There were no differences between groups in any of the variables analyzed. Therefore, remotely supervised physical exercise could be adequate to achieve long-term adherence to a healthy lifestyle in the same way as conventional face-to-face intervention, at least in a population willing to change.


Assuntos
COVID-19 , Exercício Físico , Estilo de Vida Saudável , Humanos , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Qualidade de Vida , SARS-CoV-2
5.
Biochem J ; 413(1): 103-13, 2008 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-18352857

RESUMO

ADPRibase-Mn (Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase) was earlier isolated from rat liver supernatants after separation from ADPRibase-I and ADPRibase-II (Mg2+-activated ADP-ribose pyrophosphatases devoid of CDP-alcohol pyrophosphatase activity). The last mentioned are putative Nudix hydrolases, whereas the molecular identity of ADPRibase-Mn is unknown. MALDI (matrix-assisted laser-desorption ionization) MS data from rat ADPRibase-Mn pointed to a hypothetical protein that was cloned and expressed and showed the expected specificity. It is encoded by the RGD1309906 rat gene, which so far has been annotated simply as 'hydrolase'. ADPRibase-Mn is not a Nudix hydrolase, but it shows the sequence and structural features typical of the metallophosphoesterase superfamily. It may constitute a protein family of its own, the members of which appear to be specific to vertebrates, plants and algae. ADP-ribose was successfully docked to a model of rat ADPRibase-Mn, revealing its putative active centre. Microarray data from the GEO (Gene Expression Omnibus) database indicated that the mouse gene 2310004I24Rik, an orthologue of RGD1309906, is preferentially expressed in immune cells. This was confirmed by Northern-blot and activity assay of ADPRibase-Mn in rat tissues. A possible role of ADPRibase-Mn in immune cell signalling is suggested by the second-messenger role of ADP-ribose, which activates TRPM2 (transient receptor potential melastatin channel-2) ion channels as a mediator of oxidative/nitrosative stress, and by the signalling function assigned to many of the microarray profile neighbours of 2310004I24Rik. Furthermore, the influence of ADPRibase-Mn on the CDP-choline or CDP-ethanolamine pathways of phospholipid biosynthesis cannot be discounted.


Assuntos
Pirofosfatases/química , Pirofosfatases/metabolismo , Difosfato de Adenosina/metabolismo , Adenosina Difosfato Ribose/metabolismo , Sequência de Aminoácidos , Animais , Clonagem Molecular , Cistina Difosfato/análogos & derivados , Cistina Difosfato/metabolismo , Citidina Difosfato Colina/metabolismo , Etanolaminas/metabolismo , Feminino , Regulação da Expressão Gênica , Concentração de Íons de Hidrogênio , Fígado/enzimologia , Tecido Linfoide/metabolismo , Manganês/metabolismo , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Açúcares de Nucleosídeo Difosfato/metabolismo , Pirofosfatases/genética , Ratos , Ratos Wistar , Proteínas Recombinantes , Especificidade por Substrato , Espectrometria de Massas em Tandem
6.
Enferm Clin (Engl Ed) ; 29(5): 280-290, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29785941

RESUMO

OBJECTIVE: The objectives of this paper were to determine weight status, eating, and alcohol drinking and smoking habits of university students, to determine the association between these variables with negative self-perception of their eating habits and to assess the risk of developing eating disorders. METHOD: A cross-sectional study was carried out on 422 university students. The parameters analyzed were: nutritional status, eating habits, alcohol/ tobacco consumption, and risk of eating disorder. Logistic regression was applied to identify factors associated with a negative perception of eating habits. RESULTS: Out of the whole population that was analyzed, 5% were underweight, 16% overweight and 4% obese. Fifty-five percent of the sample analyzed did not consume five meals a day. The recommended foods for daily consumption were consumed below recommendations, while sausages/fatty meats, industrial pastries, lean meats, and fish were over-consumed. Overall, the population perceived their eating habits as good/very good (63%). Alcohol and tobacco consumption predominated at weekends. The girls were more image-conscious (80.6% vs. 66%) and fearful of gaining weight (52.5% vs. 23.9%). Almost 30% had a distorted perception of body image. There was a 12.8% risk of atypical anorexia nervosa and 4.7% of atypical bulimia nervosa. CONCLUSIONS: College students led unhealthy lifestyles, mainly due to eating habits that do not conform to the establish recommendations. More than 17% are at risk of developing an atypical eating disorder. This information may be of interest in developing preventive actions.


Assuntos
Comportamento Alimentar/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Estilo de Vida , Estudantes/psicologia , Adolescente , Adulto , Consumo de Álcool na Faculdade , Animais , Anorexia Nervosa/etiologia , Anorexia Nervosa/psicologia , Imagem Corporal/psicologia , Índice de Massa Corporal , Peso Corporal , Bulimia Nervosa/etiologia , Bulimia Nervosa/psicologia , Estudos Transversais , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Peixes , Humanos , Modelos Logísticos , Masculino , Produtos da Carne , Pessoa de Meia-Idade , Estado Nutricional , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Universidades , Adulto Jovem
7.
Microorganisms ; 7(2)2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30813265

RESUMO

Gut microbiota is composed of different microorganisms that play an important role in the host. New research shows that bidirectional communications happen between intestinal microbiota and the brain, which is known as the gut⁻brain axis. This communication is significant and could have a negative or positive effect depending on the state of the gut microbiota. Anorexia nervosa (AN) is a mental illness associated with metabolic, immunologic, biochemical, sensory abnormalities, and extremely low body weight. Different studies have shown a dysbiosis in patients with AN. Due to the gut⁻brain axis, it was observed that some of the symptoms could be improved in these patients by boosting their gut microbiota. This paper highlights some evidence connecting the role of microbiota in the AN onset and disease progress. Finally, a proposal is done to include the microbiota analysis as part of the recovery protocol used to treat AN patients. When conducting clinical studies of gut microbiota in AN patients, dysbiosis is expected to be found. Then the prescription of a personalized treatment rich in prebiotics and probiotics could be proposed to reverse the dysbiosis.

8.
PLoS One ; 10(2): e0118680, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25692488

RESUMO

Among metallo-dependent phosphatases, ADP-ribose/CDP-alcohol diphosphatases form a protein family (ADPRibase-Mn-like) mainly restricted, in eukaryotes, to vertebrates and plants, with preferential expression, at least in rodents, in immune cells. Rat and zebrafish ADPRibase-Mn, the only biochemically studied, are phosphohydrolases of ADP-ribose and, somewhat less efficiently, of CDP-alcohols and 2´,3´-cAMP. Furthermore, the rat but not the zebrafish enzyme displays a unique phosphohydrolytic activity on cyclic ADP-ribose. The molecular basis of such specificity is unknown. Human ADPRibase-Mn showed similar activities, including cyclic ADP-ribose phosphohydrolase, which seems thus common to mammalian ADPRibase-Mn. Substrate docking on a homology model of human ADPRibase-Mn suggested possible interactions of ADP-ribose with seven residues located, with one exception (Cys253), either within the metallo-dependent phosphatases signature (Gln27, Asn110, His111), or in unique structural regions of the ADPRibase-Mn family: s2s3 (Phe37 and Arg43) and h7h8 (Phe210), around the active site entrance. Mutants were constructed, and kinetic parameters for ADP-ribose, CDP-choline, 2´,3´-cAMP and cyclic ADP-ribose were determined. Phe37 was needed for ADP-ribose preference without catalytic effect, as indicated by the increased ADP-ribose Km and unchanged kcat of F37A-ADPRibase-Mn, while the Km values for the other substrates were little affected. Arg43 was essential for catalysis as indicated by the drastic efficiency loss shown by R43A-ADPRibase-Mn. Unexpectedly, Cys253 was hindering for cADPR phosphohydrolase, as indicated by the specific tenfold gain of efficiency of C253A-ADPRibase-Mn with cyclic ADP-ribose. This allowed the design of a triple mutant (F37A+L196F+C253A) for which cyclic ADP-ribose was the best substrate, with a catalytic efficiency of 3.5´104 M-1s-1 versus 4´103 M-1s-1 of the wild type.


Assuntos
Hidrolases Anidrido Ácido/química , Hidrolases Anidrido Ácido/genética , Adenosina Difosfato Ribose/metabolismo , Apirase/química , Apirase/genética , Manganês/metabolismo , Hidrolases Anidrido Ácido/metabolismo , Animais , Apirase/metabolismo , Domínio Catalítico , Humanos , Fígado/metabolismo , Modelos Moleculares , Simulação de Acoplamento Molecular , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Ratos , Homologia Estrutural de Proteína
9.
Nutr Hosp ; 29(4): 941-52, 2014 Apr 01.
Artigo em Espanhol | MEDLINE | ID: mdl-24679040

RESUMO

OBJECTIVE AND METHODS: Current research has focused on the impact of difficulties in emotional recognition and regulation and deficits in social cognition (ToM) in the predisposition and maintenance of eating disorders EDs. Though most studies have assessed adult patients, few studies have examined these characteristics in adolescent patients. This study assessed difficulties in emotional recognition and ToM in 48 adult and adolescent patients (39 Anorexia Nervosa patients, and 9 Bulimia Nervosa patients) of varying degrees of severity, who were compared with a group of healthy controls using the TAS-20, and the RME. RESULTS: The results substantiate the initial working hypothesis that difficulties in emotional recognition would be greater in both AN and BN patients as compared to controls. Moreover, these difficulties were modulated by age and the severity of the disorder i.e., severely affected adult patients had more difficulties in emotional recognition than less severely affected adolescent patients. No differences were observed according to diagnosis or BMI. Contrary to expectation in terms of the functioning of social cognition (theory of mind), both adult and adolescent AN and BN patients maintained their ability to infer the mental state of others, and performance in mentalizing task was similar to controls. Performance was slightly lower, but not statistically significant, in longterm previously treated patients than in controls. No relationship with low BMI or eating symptoms was observed. CONCLUSION: Since all of the ED patients exhibited emotional difficulties, techniques designed to enhance emotional recognition are vital for successful treatment. As difficulties become more acute as the disorder progresses, the treatment of adolescent patients must entail early therapeutic interventions designed to arrest further deterioration. In terms of ToM, the results suggest difficulties in social cognition can neither be generalized to all AN patients nor to those suffering from severe malnutrition. In long-term patients mentalization was slightly low and apparently poorly associated to difficulties in therapeutic link. These results do not lend support to the hypothesis that AN patients share the characteristics of patients affected by autistic spectrum disorders, at least not in terms of all the dimensions of ToM. These, and other controversial findings in the social cognition of EDs suggest that difficulties in mentalization cannot be generalized to all ED patients, which underscores the need for further research on the differential characteristics of AN patients with ToM disorders that goes beyond the emotional difficulties observed.


Objetivo y métodos: Actualmente se destaca la importancia de las dificultades de reconocimiento emocional y los problemas en cognición social (ToM), en la predisposición y mantenimiento de los Trastornos de Conducta Alimentaria (TCA). La mayoría de los estudios han sido realizados en pacientes adultos y pocos han analizado estas características en pacientes adolescentes. Este estudio examina las dificultades de reconocimiento emocional y cognición social en 48 pacientes con Anorexia Nerviosa (AN) y Bulimia Nerviosa (BN), adultas y adolescentes, con diversos grados de gravedad y las compara con grupos control sano. Para evaluar estas dificultades se han utilizado los siguientes cuestionarios: TAS-20 y el RME. Resultados: Conforme a lo establecido en nuestras hipótesis, las pacientes con AN y BN presentan mayores dificultades en el reconocimiento que los sujetos control. Las dificultades están moduladas por la edad y la gravedad del trastorno. Las pacientes adultas y más graves presentan más problemas en el reconocimiento emocional que las adolescentes menos graves. No se han obtenido diferencias en función del diagnóstico ni del índice de masa corporal (IMC). Contrariamente a lo esperado en la hipótesis sobre la teoría de la mente, las pacientes AN y BN, adultas y adolescentes mantienen intacta su capacidad para atribuir estados mentales a otros, realizando la tarea de mentalización de forma similar a los sujetos control. Únicamente las pacientes con más tratamientos previos y mayor duración del trastorno muestran un rendimiento ligeramente inferior. No existe relación con el IMC ni con los síntomas alimentarios. Conclusiones: Dado que todas las pacientes TCA tienen dificultades emocionales, es esencial que se introduzcan técnicas terapéuticas que faciliten el reconocimiento y la aceptación en el tratamiento. Puesto que las dificultades se intensifican en el transcurso del trastorno, los tratamientos de pacientes adolescentes tienen que incluir intervenciones terapéuticas tempranas que impidan este deterioro. Por lo que respecta a la ToM, los resultados sugieren que las dificultades de cognición social no son propias de todas las pacientes AN, incluso con un IMC muy bajo. En pacientes de larga evolución la mentalización es ligeramente inferior y parece estar asociada, muy débilmente, a las dificultades de vínculo terapéutico. Estos y otros hallazgos controvertidos en cognición social en TCA, sugieren que no es posible generalizar las dificultades de mentalización a todos los pacientes con TCA e instan a realizar más investigaciones que permitan descubrir las características diferenciales de las pacientes AN con alteraciones de ToM, más allá de las dificultades de vínculo observadas.


Assuntos
Emoções , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Teoria da Mente , Adolescente , Adulto , Envelhecimento/psicologia , Anorexia/psicologia , Bulimia/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Nutr Hosp ; 31(3): 1413-22, 2014 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-25726241

RESUMO

OBJECTIVES: To analyse the presence of heightened sensory sensitivity in patients with anorexia nervosa, which seems similar but not identical to that described in patients with unexplained somatic symptoms or body dysmorphic disorder. METHODS: We developed a sensory sensitivity scale in eating disorders (SASTCA), which measures the intensity of the response to specific somatosensory stimuli. The scale was completed by 48 patients with anorexia and a control group of 31 participants matched in age, sex and social and educational level. The results were compared with those obtained with the Barsky Somatosensory Amplification Scale (SSAS). RESULTS: The reliability (Cronbach's/alpha, 0.946; Guttman/ split-half, 0.936) and validity (ROC, 0.933) of the SASTCA scale are indicative of its high sensitivity and specificity. The anorexia group had a significantly higher mean score on the SASTCA scale than the control group (p<.001). Similarly, the patients with anorexia had a significantly higher mean value on the SSAS than the participants in the control group (p<.01), although the difference was less extreme. The 2 scales correlated positively (r=.634). DISCUSSION: These preliminary results suggest the presence in Anorexia of heightened sensory sensitivity which differs from the sensitivity of the control group. This sensitivity has a significant relationship with that described in patients with somatic complaints about health (SSD) or appearance (BDD). Could this heightened sensory sensitivity help us to explain the process of forming the distorted body self-concept (I'm fat, sick, ugly) in all these patients? Once its presence has been confirmed in other patients with anorexia, their relatives and other patients with somatic disorders this heightened sensitivity could constitute the somatic endophenotype of anorexia?


Objetivo: destacar la presencia de una sensibilidad extrema hacia estímulos externos e internos (Amplificación Somatosensorial) en pacientes con Anorexia, similar pero no idéntica, a la descrita en pacientes con unexple somatic symtoms. Método: Se ha elaborado una escala de Amplificación Somatosensorial para Trastornos de la Conducta Alimentaria, (SASTCA), que mide la intensidad de la respuesta hacia estímulos somatosensoriales específicos. La escala ha sido cumplimentada por un grupo de 48 pacientes anoréxicas y un grupo control de 31 sujetos emparejados en edad, sexo y nivel socioeducativo. Los resultados se han comparado con los obtenidos en la escala SSAS de Barsky. Resultados: La Fiabilidad (Alfa de Cronbach 0,946; dos mitades de Guttman 0,936) y la Validez (ROC, 0,933), son indicativas de elevada sensibilidad y especificidad de la escala SASTCA. El grupo de pacientes presenta una media 58,73 12,38, significativamente superior al grupo control 37,81 7,47, (=0,001). Las pacientes presentan en la escala SSAS una media 31,21 6,68 significativamente superior al grupo control 26,58 5,49 (=0,01), aunque la diferencia es menos extremada. Ambas escalas correlacionan positivamente. 0,634 Conclusiones: Los resultados sugieren la presencia en AN. de una sensibilidad extrema hacia estímulos somatosensoriales. ¿Podria esta elevada sensibilidad sensorial ayudarnos a explicar el proceso de formación del auto-concepto distorsionado ("gordo, enfermo, feo") de estos pacientes? De confirmar su presencia en otras muestras de pacientes con anorexia, en sus familiares y en diferentes pacientes somatomorfos o TCA, esta elevada sensibilidad podría considerarse el endofenotipo somatomorfo del trastorno anoréxico.


Assuntos
Anorexia Nervosa/complicações , Endofenótipos , Hiperestesia/complicações , Gravidade do Paciente , Estimulação Física , Adulto , Anorexia Nervosa/psicologia , Área Sob a Curva , Imagem Corporal , Estudos de Casos e Controles , Estudos Transversais , Suscetibilidade a Doenças , Emoções , Feminino , Humanos , Hiperestesia/diagnóstico , Hiperestesia/psicologia , Masculino , Exame Neurológico , Valor Preditivo dos Testes , Psicometria , Curva ROC , Reprodutibilidade dos Testes , Autoimagem , Transtornos Somatoformes/diagnóstico , Inquéritos e Questionários , Adulto Jovem
11.
PLoS One ; 7(7): e42249, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22848751

RESUMO

The ADPRibase-Mn-like protein family, that belongs to the metallo-dependent phosphatase superfamily, has different functional and structural prototypes. The functional one is the Mn(2+)-dependent ADP-ribose/CDP-alcohol diphosphatase from Rattus norvegicus, which is essentially inactive with Mg(2+) and active with low micromolar Mn(2+) in the hydrolysis of the phosphoanhydride linkages of ADP-ribose, CDP-alcohols and cyclic ADP-ribose (cADPR) in order of decreasing efficiency. The structural prototype of the family is a Danio rerio protein with a known crystallographic structure but functionally uncharacterized. To estimate the structure-function correlation with the same protein, the activities of zebrafish ADPRibase-Mn were studied. Differences between zebrafish and rat enzymes are highlighted. The former showed a complex activity dependence on Mn(2+), significant (≈25%) Mg(2+)-dependent activity, but was almost inactive on cADPR (150-fold less efficient than the rat counterpart). The low cADPR hydrolase activity agreed with the zebrafish genome lacking genes coding for proteins with significant homology with cADPR-forming enzymes. Substrate-docking to zebrafish wild-type protein, and characterization of the ADPRibase-Mn H97A mutant pointed to a role of His-97 in catalysis by orientation, and to a bidentate water bridging the dinuclear metal center as the potential nucleophile. Finally, three structural elements that delimit the active site entrance in the zebrafish protein were identified as unique to the ADPRibase-Mn-like family within the metallo-dependent phosphatase superfamily.


Assuntos
Adenosina Difosfato Ribose/metabolismo , Cistina Difosfato/metabolismo , Manganês/metabolismo , Pirofosfatases/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra , Animais , Sítios de Ligação , Domínio Catalítico , AMP Cíclico/metabolismo , Ativação Enzimática/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Magnésio/farmacologia , Simulação de Acoplamento Molecular , Mutação , Pirofosfatases/química , Pirofosfatases/genética , Ratos , Especificidade por Substrato , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/genética
12.
FEBS Lett ; 583(10): 1593-8, 2009 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-19379742

RESUMO

Cyclic ADP-ribose (cADPR) metabolism in mammals is catalyzed by NAD glycohydrolases (NADases) that, besides forming ADP-ribose, form and hydrolyze the N(1)-glycosidic linkage of cADPR. Thus far, no cADPR phosphohydrolase was known. We tested rat ADP-ribose/CDP-alcohol pyrophosphatase (ADPRibase-Mn) and found that cADPR is an ADPRibase-Mn ligand and substrate. ADPRibase-Mn activity on cADPR was 65-fold less efficient than on ADP-ribose, the best substrate. This is similar to the ADP-ribose/cADPR formation ratio by NADases. The product of cADPR phosphohydrolysis by ADPRibase-Mn was N(1)-(5-phosphoribosyl)-AMP, suggesting a novel route for cADPR turnover.


Assuntos
Adenosina Difosfato Ribose/química , ADP-Ribose Cíclica/química , Manganês/metabolismo , Pirofosfatases/química , Adenosina Difosfato Ribose/metabolismo , Animais , ADP-Ribose Cíclica/metabolismo , Hidrólise , Modelos Moleculares , Pirofosfatases/metabolismo , Ratos , Especificidade por Substrato
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