Pegzilarginase is an enhanced human arginase
that enzymatically depletes the amino acid arginine.
Enzyme abbreviations are as follows: ADC, arginine decarboxylase; ARG, arginase
; GAD, glutamate decarboxylase; NOS, NO synthase; ODC, ornithine decarboxylase; P5CR, pyrroline-5-carboxylate reductase; P5CS, pyrroline-5-carboxylate synthetase.
From the foregoing, it can be concluded that the use of arginase
inhibitors is necessary to increase the production of nitric oxide, which helps prevent the formation of endothelial dysfunction.
MDSCs have potent immunomodulatory properties due to their expression and activity of arginase
, NOS2, IDO, NADPH, IL-10, and prostaglandin [29, 30, 38, 39,45, 46].
Kuo, "Macrophage arginase
promotes tumor cell growth and suppresses nitric oxide-mediated tumor cytotoxicity," Cancer Research, vol.
Quantification of Nitric Oxide, Arginase
Activity, and IL-10.
After many doctor visits, lots of tests, and months of fear, a Metabolic Specialist diagnosed me with a rare genetic defect, arginase
deficiency, a part of the urea cycle group of birth defects.
Manganese homeostasis is of great importance to the organism because it is an essential mineral for the activity of several enzymes such as pyruvate carboxylase, which catalyzes the conversion of pyruvate to oxaloacetate (16); arginase
, which converts arginine to urea (17); and manganese superoxide dismutase (MnSOD), critical for antioxidant defense (18).
In addition, haemolysis releases Arginase
, which degrades Arginine the substrate for endothelial NO synthase resulting in decreased NO production.
Furthermore, arginine is the common substrate for both arginase
and NOS and the increase of arginase
activity reduces the arginine needed for NO production by NOS, a status which can cause endothelial dysfunction [105, 111].
Luckner et al., "Suppression of T-cell functions by human granulocyte arginase
," Blood, vol.
MDSCs can adopt multiple mechanisms to induce immunosuppression, including production of arginase
1 and inducible nitric oxide synthase, leading to T-cell inhibition [19,20].