Arilesterasa. Aspectos metodológicos y funcionales de una enzima clave en la enfermedad cardiovascular. Parte II

Resumen

Cardiovascular diseases (CVD) are the first cause of death in developed countries and it is estimated that by 2010 they will also be the leading cause of death in developing countries. Epidemiologic studies have demonstrated that reduction of total serum cholesterol decreases prevalence and death rates associated with ischemic cardiopathy and CVD. Furthermore, a high concentration of LDL is considered a risk factor, while high levels of HDL are thought to be a protective factor. Many authors have suggested that HDL-bound PON1 enzyme may confer the protective effects to HDL. PON1 is an enzyme with several in vitro activities: paraoxonase, arylesterase, and lactonase. It has been reported that PON1 inhibits LDL and HDL peroxidation, as well as it facilitates the cholesterol reverse transport, helping to inhibit the development of atherosclerosis. Its native substrates, its in vivo mechanism of action and its molecular targets in the human body are still unknown. Nevertheless, calorimetric and spectrophotometric methods, very often employed but reaching to low very precise and sensible results, to determine its arylesterase activity have been developed. In this paper several aspects of this enzyme such as the mechanism of action, the regulation by substrates, genes and diet, are reviewed. Moreover, we present a method that uses a serum mimetic buffer that permits to obtain more precise and reproductible results of the arylesterase activity in humans and mice. Furthermore the relationship between PON1 polymorphisms and arylesterase activity is also tested in subjects at increased CVD-risk.