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 journalArticlepeer-review

27 Citations (Scopus)
1 Downloads (Pure)

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 - 27 Feb 2018

Keywords

  • Cardiovascular biology
  • Predictive markers

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