Current Enzyme Inhibition - Volume 4, Issue 2, 2008

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have well-recognized cardio-beneficial effects that include reductions in atherosclerotic lesions and mortality from myocardial infarction, stroke, and sudden cardiac death. In contrast, evidence suggests that more than 30,000 premature coronary deaths per year in the US alone are associated with consumption of high levels of trans isomers of unsaturated fatty acids, or trans fatty acids (TFAs). Epidemiological evidence from four large cohort studies overwhelmingly supports the conclusion that TFAs are linked to coronary heart disease (CHD). CHD in patients is associated with pathological vascular remodeling (PVR) and impaired compensatory vascular remodeling (CVR). PVR is characterized by thickening of vessel walls, reduction in elasticity, and occlusion of vessels, resulting in restricted blood flow. CVR represents a physiological process whereby vessels from a pre-existing arteriolar network develop into collateral arteries, effectively bypassing the site of arterial occlusion. The structure and function of vascular endothelial cell membranes are altered by both PVR and CVR. Oxidative stress and the induction of endothelial adhesion molecules promote PVR and inhibit CVR. It is known that n-3 PUFAs inhibit the release of soluble adhesion molecules and proinflammatory cytokines whereas TFA consumption has been linked to an increased release of these proinflammatory mediators. However, it is not known whether the changes in cell membrane composition induced by n-3 PUFAs or TFAs impact development of PVR and CVR directly or whether the changes result indirectly from altered expression and/or release of proinflammatory mediators. This review summarizes studies suggesting that n-3 PUFAs and TFAs have opposing effects on endothelial cells and that their effects on the endothelium might play an important role in vascular remodeling.

It is known that nitric oxide (NO) realizes its basic physiological effects by affecting activity of specific enzymes, such as guanylate cyclase and caspase. Since NO itself in physiological conditions is a short-lived substance, it is considered that it acts by means of some metabolites such as nitrosothiols and some nitro-compounds, which may serve as NO - donors. These NO metabolites are relatively stable substances and their concentrations in biological tissues are also relatively stable. But in this case it is unclear how their physiological effects are controlled. Could they, for example, respond to the certain factors, be accumulated in the right place at the right time or just dissociate releasing NO? In scientific literature these questions remain unanswered. In this review we present the result of our analysis of the available scientific data from the different researchers on the interaction of some NO-donors with guanylate cyclase, caspase and catalase. We propose that NO-like effects of these NOdonors are not the result of only their simple dissociation with releasing of NO. Mostly it is a complex process that starts with initial transformation of these substances into nitrosyl-iron complexes. NO-group of this complex becomes available for the interaction as nitrosation agent only at the moment of destabilization of the complex, which can be initiated by variation of iron associated ligands included in the complex. The ligand content in the medium can be changed depending on physiological conditions.

Cancer cells enter the circulation and attach to endothelial cells to pass through them and migrate over a distance to enter the tissue of the metastatic organ to proliferate there. In the same way, neutrophils drift in blood and adhere loosely to adhesive molecules on the endothelial cells in an inflamed area. They roll along the endothelial cells and then adhere closely to the endothelial cells to penetrate vessel wall. Neutrophils can destroy the basement membrane and migrate over a distance to fight against foreign bodies. Thus, the process that both of them follow is quite the same. Neutrophil elastase (NE) is a neutral serine protease which has broad substrate specificity under the physiological conditions, and its excessive production results in digestion of not only elastin, but also other extracellular matrix proteins. This minireview summarizes our recent experimental and clinical studies on NE/NE inhibition and cancer/cancer treatment based on our original view point.

Catalases are enzymes composed of a protein and a prosthetic group made up of iron porphyrin. The aim of the present research, was to study the catalytic mechanism of catalase on organic hydroperoxides rather than on hydrogen peroxide, when operating in organic solvents such as decane or hexane. The investigation was performed using gas chromatography and amperometry to analyse the reagents and reaction products of the catalytic reaction of catalase on tertbutylhydroperoxide or on cumene hydroperoxide, carried out in decane. The analytical results pointed to the hypothesis that, in this case, the organic solvent is involved in the reaction. In the absence of other reducing agents, therefore, a small percentage of it is oxidized and this redox reaction presumably involves the molecular oxygen present in solution, the consumption of which is determined experimentally through amperometry. This interpretation was confirmed in the gas chromatograms performed by the appearance of new peaks formed as a result of the enzymatic reaction in decane which are presumably to be attributed to species derived from the oxidation of decane, such as decanol.