Homoarginine and inhibition of human arginase activity: kinetic characterization and biological relevance

Scientific Reports
S TommasiArduino A Mangoni

Abstract

The inhibition of arginase, resulting in higher arginine (ARG) availability for nitric oxide synthesis, may account for the putative protective effect of homoarginine (HOMOARG) against atherosclerosis and cardiovascular disease. However, uncertainty exists regarding the significance of HOMOARG-induced arginase inhibition in vivo. A novel UPLC-MS method, measuring the conversion of ARG to ornithine (ORN), was developed to determine arginase 1 and arginase 2 inhibition by HOMOARG, lysine (LYS), proline (PRO), agmatine (AG), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and NG-Monomethyl-L-arginine (L-NMMA). Plasma HOMOARG, ARG and ORN concentrations were further measured in 50 healthy older adults >65 years (27 males and 23 females). HOMOARG inhibited arginase 1 with IC50 and Ki values of 8.14 ± 0.52 mM and 6.1 ± 0.50 mM, and arginase 2 with IC50 and Ki values of 2.52 ± 0.01 mM and 1.73 ± 0.10 mM, respectively. Both arginase isoforms retained 90% activity vs. control when physiological HOMOARG concentrations (1-10 µM) were used. In partial correlation analysis, plasma HOMOARG was not associated with ARG (P = 0.38) or ARG/ORN ratio (P = 0.73) in older adults. Our results suggest that arginase inhibition is...Continue Reading

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Citations

May 29, 2018·European Journal of Clinical Investigation·Angelo ZinelluArduino A Mangoni
Aug 10, 2018·Expert Opinion on Therapeutic Patents·Rakhi DhankharRajeev Kumar Kapoor
Jan 18, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Katrin NitzDorothee Atzler
Mar 15, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Ekaterina S KaretnikovaRoman N Rodionov
Jul 4, 2019·Age and Ageing·Arduino A MangoniSalvatore Sotgia
Jul 30, 2020·International Journal of Molecular Sciences·Gonçalo S ClementePhilip H Elsinga
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Methods Mentioned

BETA
electrophoresis

Clinical Trials Mentioned

NCT02843009

Software Mentioned

SPSS Statistics
Waters MassLynx
SPSS
EnzFitter
ImageQuant

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