Arginase-2, mitochondrial

Definition:

May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to nitric oxid synthase (NOS). Arginine metabolism is a critical regulator of innate and adaptive immune responses. Seems to be involved in negative regulation of the survival capacity of activated CD4(+) and CD8(+) T cells. May suppress inflammation-related signaling in asthmatic airway epithelium. May contribute to the immune evasion of H.pylori by restricting M1 macrophage activation and polyamine metabolism (By similarity). In fetal dendritic cells may play a role in promoting immune suppression and T cell TNF-alpha production during gestation. Regulates RPS6KB1 signaling, which promotes endothelial cell senescence and inflammation and implicates NOS3/eNOS dysfunction. Can inhibit endothelial autophagy independently of its enzymatic activity implicating mTORC2 signaling. Involved in vascular smooth muscle cell senescence and apoptosis independently of its enzymatic activity. Since NOS is found in the penile corpus cavernosum smooth muscle, the clitoral corpus cavernosum and the vagina, arginase-2 plays a role in both male and female sexual arousal.

References:

[1]. Yuyan Xiong, et al. Arginase-II induces vascular smooth muscle cell senescence and apoptosis through p66Shc and p53 independently of its l-arginine ureahydrolase activity: implications for atherosclerotic plaque vulnerability. J Am Heart Assoc. 2013 Jul 5;2(4):e000096. [Content Brief]

[2]. Weiling Xu, et al. Increased mitochondrial arginine metabolism supports bioenergetics in asthma. J Clin Invest. 2016 Jul 1;126(7):2465-81. [Content Brief]

[3]. Roger Geiger, et al. L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. Cell. 2016 Oct 20;167(3):829-842.e13. [Content Brief]

[4]. Naomi McGovern, et al. Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2. Nature. 2017 Jun 29;546(7660):662-666. [Content Brief]

[5]. Evis Cama, et al. Human arginase II: crystal structure and physiological role in male and female sexual arousal. Biochemistry. 2003 Jul 22;42(28):8445-51. [Content Brief]

[6]. Gautham Yepuri, et al. Positive crosstalk between arginase-II and S6K1 in vascular endothelial inflammation and aging. Aging Cell. 2012 Dec;11(6):1005-16. [Content Brief]

[7]. Yuyan Xiong, et al. ARG2 impairs endothelial autophagy through regulation of MTOR and PRKAA/AMPK signaling in advanced atherosclerosis. Autophagy. 2014;10(12):2223-38. [Content Brief]

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