RESUMO
AMP-deaminase (EC 3.5.4.6) is an enzyme of nucleotide breakdown involved in regulation of adenine nucleotide pool in mammalian cells. Reaction catalysed by AMP-deaminase constitutes a rate-limiting step in adenine nucleotide catabolism in liver. In this study kinetic and regulatory properties of AMP-deaminase purified from normal and cirrhotic human liver were investigated. In comparison to AMP-deaminase extracted from the normal human liver, AMP-deaminase extracted from the cirrhotic liver was less sensitive towards substrate analogues, and only a very limited response towards pH and adenylate energy charge changes tested for enzyme isolated from this tissue source had been observed. At physiological pH 7.0, in the absence and in the presence of important allosteric effectors (ATP, ADP, GTP and orthophosphate), AMP-deaminases from the two sources studied manifested different regulatory profiles, with half-saturation constant (S0.5) values being distinctly higher for the enzyme extracted from the pathological organ. In contrast to AMP-deaminase isolated from the normal, healthy liver, where presence of relatively large (68 kDa) protein fragment was also detected, only smaller protein fragments were identified, while SDS-PAG electrophoresis of AMP-deaminase isolated from the cirrhotic liver was performed. The obtained results indicate clearly that advanced proteolytic processes occurring in the cirrhotic liver may affect structural integrity of AMP-deaminase studied, making enzyme less active and less sensitive to regulatory action of important allosteric effectors.
Assuntos
AMP Desaminase/química , AMP Desaminase/metabolismo , Cirrose Hepática Alcoólica/enzimologia , Adulto , Regulação Alostérica , Estudos de Casos e Controles , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Peso Molecular , Especificidade por SubstratoRESUMO
The importance of dyslipidemia in the development of cardiovascular disease is now recognized as a central factor of equal, if not greater significance than any other risk factor. Although correction of high level of low-density lipoproteins (LDL) has been regarded now as the main goal of therapy, it has now been reaffirmed that the contribution of low level of high-density lipoproteins (HDL) to the risk of ischaemic heart disease should also be considered. In the therapy of dislipidemias with hipertriglyceridemia and decreased level of HDL lipoprotein fibrates play an especially important role. In the article the molecular mechanism of fibrates action is presented.
Assuntos
Bezafibrato/uso terapêutico , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Hiperlipidemias/complicações , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Hepatócitos/efeitos dos fármacos , Humanos , Hiperlipidemias/genética , Isquemia Miocárdica/genética , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/genética , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaAssuntos
Doenças Cardiovasculares/terapia , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Canais de Potássio/efeitos dos fármacos , AMP Desaminase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Doenças Cardiovasculares/metabolismo , Humanos , Mutação , Miocárdio/metabolismo , Canais de Potássio/genética , Canais de Potássio/metabolismoRESUMO
Clinical studies indicate that treatment with statins significantly reduces the incidence of myocardial infarction and death from cardiovascular diseases. Quite recently statins were found to exert a direct cardiovascular effect, which is independent on their well-known cholesterol lowering action. In this article current views on the role of statins in improvement of function of vascular endothelium are presented.
