Arginase: an old enzyme with new tricks

Abstract

Arginase has roots in early life forms. It converts L-arginine to urea and ornithine. The former provides protection against NH3; the later serves to stimulate cell growth and other physiological functions. Excessive arginase activity in mammals has been associated with cardiovascular and nervous system dysfunction and diseases. Two relevant aspects of this elevated activity may be involved in these disease states. First, excessive arginase activity reduces the supply of L-arginine needed by nitric oxide (NO) synthase to produce NO. Second, excessive production of ornithine leads to vascular structural problems and neural toxicity. Recent research has identified inflammatory agents and reactive oxygen species (ROS) as drivers of this pathologic elevation of arginase activity and expression. Here we review involvement of arginase in cardiovascular and nervous system dysfunction and discuss potential therapeutic interventions targeting excess arginase.

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“…Because NO serves to relax the smooth muscles of the corpus cavernosum, inhibition of ARG, at this time, is useful for increasing the supply of the substrate to the action of eNOS [93].…”

“…It is interesting to note that ARG activity is related to tumour progression, since the formation of polyamines and proline that are the result of enzyme action can contribute to cell proliferation and tumour growth, as shown by studies that have found a relationship of risk between the increased expression of ARG 2 and the appearance of disease [93,105]. Thus, ARG inhibition has the potential to curb this process, which might work in favour of the action of other anticancer substances.…”

“…There remains considerable controversy about the role of the expression of ARG in different conditions like atherosclerosis and other forms of vessel inflammation. For instance, hyperglycaemia of diabetes causes ED via the activation of p38 MAPK, which produces the upregulation of ARG 1 in coronary arteries and the increased expression of ARG 2 in mesenteric arteries [44,122].…”

“…There is also growing evidence that ARG expression and activation can be detrimental or beneficial depending on the biological context that is analysed. For this reason, it is not yet completely understood which ARG isoform should be targeted in order to achieve better outcomes [26,44,84].…”

“…Therapies utilising ARG inhibitors in systemic doses are used in the treatment of parasitic diseases without significant adverse effects [44].…”