RESUMO
Incorporation of fatty acids into phospholipids as well as cholesterol and phospholipid concentration has been investigated using samples of rat liver homogenate, Krebs-Ringer-phosphate buffer (pH = 7.4), containing 0.3% albumin, fatty acid mixture and glycerol. The addition of kynurenine, kynurenic, xanthurenic, picolinic, and 5-hydroxyindoleacetic acids to incubation medium for phospholipid biosynthesis in vitro induced the elevation of cholesterol/phospholipid ratio, cholesterol concentration in samples, an increase of saturated and a decrease of polyunsaturated fatty acids, especially arachidonic acid incorporation into phospholipids. It allowed us to suggest that these metabolites of tryptophan can decrease the membrane fluidity, depress cell cycle, cell transformation and may stimulate cholesterol precipitation. The addition of tryptophan, 3-hydroxykynurenine, 3-hydroxyanthranilic, quinolinic, nicotinic acids, serotonin together with iproniasid, acetylserotonin, and melatonin to incubation medium for phospholipid biosynthesis in vitro induced an inverse relationship. Tryptophan and above mentioned metabolites decreased cholesterol/phospholipid ratio, cholesterol concentration in samples and incorporation of saturated fatty acids into phospholipids. The incorporation of polyunsaturated fatty acids, especially arachidonic acid increased. It allowed us to suggest that tryptophan and these metabolites, may increase membrane fluidity, stimulate cell cycle, cell transformation and can protect against cholesterol precipitation.
Assuntos
Fígado/efeitos dos fármacos , Fluidez de Membrana/efeitos dos fármacos , Triptofano/análogos & derivados , Triptofano/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Ácido Hidroxi-Indolacético/farmacologia , Cinética , Ácido Cinurênico/farmacologia , Cinurenina/farmacologia , Fígado/citologia , Fígado/metabolismo , Masculino , Fluidez de Membrana/fisiologia , Lipídeos de Membrana/metabolismo , Fosfolipídeos/biossíntese , Fosfolipídeos/metabolismo , Ácidos Picolínicos/farmacologia , Ratos , Ratos Wistar , Xanturenatos/farmacologiaAssuntos
Colesterol/metabolismo , Cinurenina/farmacologia , Fígado/metabolismo , Fluidez de Membrana/efeitos dos fármacos , Fosfolipídeos/metabolismo , Pteridinas/farmacologia , Animais , Ácidos Graxos/análise , Cinética , Fígado/efeitos dos fármacos , Masculino , Lipídeos de Membrana/metabolismo , Ratos , Ratos WistarAssuntos
Pressão Sanguínea , Catecolaminas/sangue , Glomerulonefrite Membranoproliferativa/sangue , Glomerulonefrite Membranoproliferativa/fisiopatologia , Hipertensão/fisiopatologia , Cinurenina/sangue , Triptofano/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Diástole , Dopamina/sangue , Epinefrina/sangue , Humanos , Hipertensão/sangue , Hipertensão/complicações , Norepinefrina/sangue , Valores de Referência , SístoleAssuntos
Cinurenina/farmacologia , Metabolismo dos Lipídeos , Fosfato de Piridoxal/deficiência , Animais , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Rim/metabolismo , Cinurenina/metabolismo , Fígado/metabolismo , Masculino , Miocárdio/metabolismo , Fosfolipídeos/metabolismo , Fosfato de Piridoxal/farmacologia , Ratos , Ratos EndogâmicosRESUMO
The present work is divided into two parts: clinical observations and experimental investigations. The endogenic formation of nicotinic acid was decreased in all patients with ischaemic heart disease, and we have found an increased accumulation of kynurenine in blood serum after tryptophan loading in many cases - a clear indication of pyridoxal-5-phosphate (P-5-P) deficiency in the organism. The results of experimental investigations showed that L-kynurenine sulphate initiates cardiac dysrhythmias as well as dystrophic changes in cardiomyocytes. Both the clinical observations and experimental investigations point out a previously unknown pathogenetic mechanism for the ischaemic heart disease, and for bradyarrhythmia as well as myocardial cell failure, caused by P-5-P deficiency in the organism.
