Identificador: TDX:480
Autores: Ferré Pallàs, Natàlia
Resumen:
1. IntroductionParaoxonase (PON) is an ester hidrolase that catalyzes the hydrolysis of some xenobiotics, such as organophosforates, unsaturated aliphatic esters, aromatic carboxylic esters, and possibly, carbamates. The PON gene family contains, in mammals, at least tree members, PON1, PON2 and PON3. The most known of these gene products is PON1, called 'paraoxonase' or 'arilesterase' depending on the substrate used to measure its activity.PON1 is known to be tightly bound with HDL in serum, and some studies suggest that this association contributes to the protection conferred by HDL against LDL oxidation, since PON1 is capable to hydrolyze lipid peroxides located in oxidized LDL. There are some polymorphisms in PON1 gene, the most known being Gln/Arg substitution at position 192 and Met/Leu substitution at position 55. These polymorphisms are known to influence the activity and concentration of PON1. Some authors have associated these polymorphisms with PON1's ability to protect against LDL oxidation. LDL oxidation plays a key role in arteriosclerosis and, some studies have investigated the relation between PON1 protein, polymorphisms and these disease. The results had been inconclusive.The liver plays a key role in the synthesis of serum PON1. PON1 gene expression has been observed only in the liver, and in vitro biochemical studies indicate properties shared by hepatic and serum PON1 what supports the hypothesis of a common identity for both enzymes. The possible function of PON1 in liver diseases is not known. 2. AimsFirst study: to assess whether PON1 polymorphisms at positions 55 and 192 or their phenotypic expression are associated with the incidence of myocardial infarction in a Mediterranean population.Second study: to investigate the relationship between PON1 activity in hepatic microsomes, lipid peroxidation and hepatic damage progression in rats with CCl4 induced cirrhosis.Third study: to investigate a) the relationship between serum PON1 activity and the degree of hepatic damage in patients with chronic liver disease; b) the influence of genetic variability on serum PON1 activity in these patients and; c) the efficacy of serum PON1 activity measurement, alone and in combination with the standard liver function tests, in the assessment of liver damage.3. Results and discussionFirst study: Paraoxonase Gln-Arg (192) and Leu-Met (55) gene polymorphisms and enzyme activity in a population with a low rate of coronary heart disease. Clinical Biochemistry 2002; 35: 197-203.Second study: Hepatic paraoxonase activity alterations and free radical production in rats with experimental cirrhosis. Metabolism 2001; 50: 997-1000.Third study: Serum paraoxonase activity: a new additional test for the improved evaluation of chronic liver damage. Clinical Chemistry 2002; 48: 261-268.
Repositori URV