RESUMO
Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl--dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4-]2- and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3-]-. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.
Assuntos
Biologia Computacional , Creatina/metabolismo , Doença , Saúde , Animais , Transporte Biológico , Creatina/biossíntese , Creatina/química , Creatina Quinase/metabolismo , HumanosRESUMO
OBJECTIVES: To determine the metabolite levels (myo-inositol [MI], choline [Cho], glutamate [Glx], creatine [Cr] and N-acetylaspartate [NAA]) visible on magnetic resonance spectroscopy in patients with chronic hepatic failure, before and after liver transplantation and to correlate these data with results of neuropsychiatric tests and clinical findings. METHODS: Twenty five patients with chronic hepatic failure from the Liver Transplantation Unit of the Federal University of Parana were prospectively studied. Patients were submitted to clinical evaluation and magnetic resonance spectroscopy. Thirty healthy volunteers also submitted to the same evaluations. Sixteen of the 25 patients were evaluated after liver transplantation. RESULTS: Before liver transplantation, significant reductions in MI/Cr and Cho/Cr and a significant increase in Glx/Cr were observed in patients with hepatic encephalopathy compared with healthy subjects. The Ross's criteria for spectroscopic diagnosis of the hepatic encephalopathy (MI/Cr and Cho/Cr lower than 2 SD of controls) demonstrated a sensitivity of 61.54%, specificity of 91.67% and accuracy of 76%, further Cho/Cr was the best parameter. Spectroscopy after liver transplantation showed changes in the metabolite ratios compared with the pretransplantation status. CONCLUSION: Magnetic resonance spectroscopy permits an accurate diagnosis of hepatic encephalopathy. Improvement of metabolic ratios after liver transplantation suggests an important role of MI and Cho in the development of hepatic encephalopathy.
Assuntos
Encéfalo/metabolismo , Metabolismo Energético/fisiologia , Encefalopatia Hepática/metabolismo , Transplante de Fígado , Espectroscopia de Ressonância Magnética , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Estudos de Casos e Controles , Colina/análise , Creatina/análise , Creatina/biossíntese , Feminino , Encefalopatia Hepática/cirurgia , Humanos , Inositol/análise , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJETIVOS: Determinar os níveis dos metabólitos (mio-inositol [MI], colina [Cho], glutamina [Glx], creatina [Cr] e N-acetilaspartato [NAA]) por meio da espectroscopia por ressonância magnética em portadores de hepatopatia crônica, antes e após o transplante hepático, correlacionando com a avaliação clínica. MÉTODOS: Foram estudados prospectivamente 25 pacientes portadores de hepatopatia crônica do Serviço de Transplante Hepático da Universidade Federal do Paraná por meio de avaliação clínica e espectroscópica. Trinta voluntários sadios formaram o grupo controle, sendo submetidos às mesmas avaliações. Dezesseis dos 25 pacientes também foram avaliados após o transplante. RESULTADOS: Antes do transplante hepático reduções significativas nos índices de MI/Cr e Cho/Cr e aumento significativo no índice de Glx/Cr foram observadas nos pacientes portadores de encefalopatia hepática comparados ao grupo controle. Os critérios quantitativos de Ross para diagnóstico espectroscópico da encefalopatia hepática (MI/Cr e Cho/Cr < média + 2 desvios padrão do grupo controle) demonstraram uma sensibilidade de 61,54 por cento, especificidade de 91,67 por cento e precisão de 76 por cento, sendo que a Cho/Cr foi o melhor parâmetro isolado. A espectroscopia após o transplante mostrou mudanças nos índices metabólicos comparados com o status pré-transplante. CONCLUSÃO: A espectroscopia permite um diagnóstico preciso da encefalopatia hepática. A melhora dos níveis metabólicos após o transplante hepático sugere um importante papel do MI e da Cho no desenvolvimento da encefalopatia hepática.
OBJECTIVES: To determine the metabolite levels (myo-inositol [MI], choline [Cho], glutamate [Glx], creatine [Cr] and N-acetylaspartate [NAA]) visible on magnetic resonance spectroscopy in patients with chronic hepatic failure, before and after liver transplantation and to correlate these data with results of neuropsychiatric tests and clinical findings. METHODS: Twenty five patients with chronic hepatic failure from the Liver Transplantation Unit of the Federal University of Parana were prospectively studied. Patients were submitted to clinical evaluation and magnetic resonance spectroscopy. Thirty healthy volunteers also submitted to the same evaluations. Sixteen of the 25 patients were evaluated after liver transplantation. RESULTS: Before liver transplantation, significant reductions in MI/Cr and Cho/Cr and a significant increase in Glx/Cr were observed in patients with hepatic encephalopathy compared with healthy subjects. The Ross's criteria for spectroscopic diagnosis of the hepatic encephalopathy (MI/Cr and Cho/Cr lower than 2 SD of controls) demonstrated a sensitivity of 61.54 percent, specificity of 91.67 percent and accuracy of 76 percent, further Cho/Cr was the best parameter. Spectroscopy after liver transplantation showed changes in the metabolite ratios compared with the pretransplantation status. CONCLUSION: Magnetic resonance spectroscopy permits an accurate diagnosis of hepatic encephalopathy. Improvement of metabolic ratios after liver transplantation suggests an important role of MI and Cho in the development of hepatic encephalopathy.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encéfalo/metabolismo , Metabolismo Energético/fisiologia , Encefalopatia Hepática/metabolismo , Transplante de Fígado , Espectroscopia de Ressonância Magnética , Ácido Aspártico/análise , Ácido Aspártico/análogos & derivados , Estudos de Casos e Controles , Colina/análise , Creatina/análise , Creatina/biossíntese , Encefalopatia Hepática/cirurgia , Inositol/análise , Estudos ProspectivosRESUMO
Arginine:glycine amidinotransferase deficiency is a treatable inborn error of creatine synthesis, characterized by mental retardation, language impairment, and behavioral disorders. We describe a patient in whom arginine:glycine amidinotransferase was diagnosed at birth and treated at 4 months with creatine supplementation. In contrast with his 2 older sisters, he had normal psychomotor development at 18 months.
Assuntos
Amidinotransferases/deficiência , Creatina/uso terapêutico , Erros Inatos do Metabolismo/terapia , Amidinotransferases/genética , Aleitamento Materno , Creatina/análise , Creatina/biossíntese , Suplementos Nutricionais , Humanos , Recém-Nascido , Espectroscopia de Ressonância Magnética , Masculino , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/genética , Leite Humano/química , Mutação , Fenótipo , Desempenho Psicomotor , Fatores de TempoRESUMO
La L-arginina es uno de los aminoácidos más versátiles desde el punto de vista metabólico y fisiológico. Entre sus funciones conocidas se incluyen: sustrato de la biosíntesis de proteínas y de péptidos bioactivos, participación en la detoxificación de amonio, liberación de hormonas, y biosíntesis de poliaminas y creatina. Las funciones de la arginina se han visto recientemente incrementadas con el descubrimiento de su papel como sustrato precursor del óxido nítrico, un efector multifuncional implicado en la vasodilatación, neurotransmisión, y con actividad antimicrobiana y antitumoral. Desde el punto de vista nutricional, la arginina es un aminoácido "condicionalmente esencial" para los mamíferos. Sus requerimientos se cubren gracias al aporte dietético y la síntesis endógena, siendo ésta última en el hombre, al parecer, suficiente para cubrir las necesidades fisiológicas habituales pero insuficiente en períodos o condiciones de elevada demanda del aminoácido. Tal situación sugiere un potencial uso terapéutico para la arginina que está comenzando a ser analizado. Esta revisión pretende resumir los conocimientos actuales sobre la síntesis de arginina y sus principales destinos metabólicos (AU)