AN IN- VITRO BIOPHYSICAL STUDY OF THE INFLUENCE OF FATTY ACIDS AND SOME DRUGS ON ATPase ACTIVITY IN PATIENTS WITH MYOCARDIAL INFARCTION

number: 
1453
English
department: 
Degree: 
Imprint: 
Medicine
Author: 
Raid Jasim Mohammed AL-Timimi
Supervisor: 
Dr. Samir Mahmood Jasim
year: 
2006

Abstract:

This review deals with the membrane – located ATPases that have a transport function. A common characteristics of these enzymes is that they catalyze the same overall reaction ( the hydrolysis of ATP to ADP and inorganic phosphate ) and utilized the free energy change of this reaction for the transport of ions against an electrochemical gradient across the membrane in which they are located. ATPases are vectorial enzymes , in that their enzymatic activity leads to the transport of an ion in a certain direction across a membrane. As the ion transport system is the principle regulator for normal cell function and there are different underlying causes for myocardial infarction ( MI ), two types of ATPases ( Na+,K+ATPase and Ca2+ATPase ) were chosen to investigate the transport alteration in MI by studying the biophysical and kinetic parameters of enzymatic reactions of ATP hydrolysis in MI patients and in a control group with and without taking medications. An in vitro study for the effect of FA and FA plus some drugs ( Actilyse, Atenolol and Isosorbide ) on ATPase activities has been investigated. Sixety subjects were enrolled in this study and subdivided into two groups .The first included 30 MI patients with a mean age of (27-67) years admitted to the emergency department with chest pain diagnosed as myocardial infarction .The second group ( control group ) is of 30 subjects with a mean age of (25-60) . Methods 1- Determination of NEFA plasma level for the MI patients and the control group. 2- Measuring the erythrocyte membrane ATPase enzyme activity which is based on the measurement free phosphate release from ATP. 3- Making an in-vitro study to explore the nature of the lipid - ATPase interaction and examining the effect of FA concentration on the ATPase activity . 4- To samples containing FA, three types of drugs were employed to study their effects on ATPase activities. 5- The activity of ATPase was measured at different temperatures and the basic thermodynamic functions of enzyme ATPase interaction ( ΔG, ΔH and ΔS ) have been estimated.
6- Measuring the Michaelis – Menten parameters ( Km and V max ) for the two types of ATPase in the control group and groups with FA and FA plus drugs of ( Actilyse, Atenolol and isosorbide ). Results
1- Plasma levels of non-esterified fatty acid exhibited elevated values after myocardial infarction. 2- Fatty acid was found to decrease the activity of the two types of ATPases. 3- Both Atenolol and Isosorbide decreased the ATPases activity, while Actilyse worked as an activator to these enzymes . 4- At high levels of fatty acid concentrations, no effect was observed on enzymes activity when different concentrations of FA were used. 5- All types of hydrolysis reactions of ATP in the presence of FA and drugs appeared spontaneous with negative values of ΔG accompanied with negative values of ΔH and ΔS. 6- All types of ATPases appeared with a highest activity at the physiological temperature 37.5 ºC. 7- Michaelis – Menten parameters ( Km and Vmax ) for the ATPases when treated with FA and drugs of Atenolol and Isosorbide appeared of lower values as compared with the corresponding values of the control group. A contrast behavior was noticed for the system FA plus Actilyse.