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

Sara Tommasi, David Elliot, Mariasole Da Boit, Stuart Gray, Benjamin Lewis, Arduino Mangoni

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    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 K i values of 8.14 ± 0.52 mM and 6.1 ± 0.50 mM, and arginase 2 with IC50 and K i 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 unlikely to play a significant role in the reported cardio-protective effects of HOMOARG.

    Original languageEnglish
    Article number3697
    Number of pages13
    JournalScientific Reports
    Volume8
    Issue number1
    DOIs
    Publication statusPublished - 2018

    Fingerprint Dive into the research topics of 'Homoarginine and inhibition of human arginase activity: kinetic characterization and biological relevance'. Together they form a unique fingerprint.

  • Cite this