A Novel Pathway for Metabolism of the Cardiovascular Risk Factor Homoarginine by alanine:glyoxylate aminotransferase 2
Rodionov RN, Oppici E, Martens-Lobenhoffer J, Jarzebska N, Brilloff S, Burdin D, Demyanov A, Kolouschek A, Leiper J, Maas R, Cellini B, Weiss N, Bode-Boeger SM (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 6
Pages Range: 35277
DOI: 10.1038/srep35277
Abstract
Low plasma concentrations of L-homoarginine are associated with an increased risk of cardiovascular events, while homoarginine supplementation is protective in animal models of metabolic syndrome and stroke. Catabolism of homoarginine is still poorly understood. Based on the recent findings from a Genome Wide Association Study we hypothesized that homoarginine can be metabolized by alanine:glyoxylate aminotransferase 2 (AGXT2). We purified human AGXT2 from tissues of AGXT2 transgenic mice and demonstrated its ability to metabolize homoarginine to 6-guanidino-2-oxocaproic acid (GOCA). After incubation of HepG2 cells overexpressing AGXT2 with isotope-labeled homoarginine-d4 we were able to detect labeled GOCA in the medium. We injected wild type mice with labeled homoarginine and detected labeled GOCA in the plasma. We found that AGXT2 knockout (KO) mice have higher homoarginine and lower GOCA plasma levels as compared to wild type mice, while the reverse was true for AGXT2 transgenic (Tg) mice. In summary, we experimentally proved the presence of a new pathway of homoarginine catabolism - its transamination by AGXT2 with formation of GOCA and demonstrated that endogenous AGXT2 is required for maintenance of homoarginine levels in mice. Our findings may lead to development of novel therapeutic approaches for cardiovascular pathologies associated with homoarginine deficiency.
Authors with CRIS profile
Involved external institutions
Otto-von-Guericke-Universität Magdeburg
Germany (DE)
Technische Universität Dresden
Germany (DE)
University of Verona / Università degli Studi di Verona
Italy (IT)
MRC London Institute of Medical Sciences
United Kingdom (GB)
Saint Petersburg State University (SPbU) / Санкт-Петербургский государственный университет (СПбГУ)
Russian Federation (RU)
Germany (DE)
Technische Universität Dresden
Germany (DE)
University of Verona / Università degli Studi di Verona
Italy (IT)
MRC London Institute of Medical Sciences
United Kingdom (GB)
Saint Petersburg State University (SPbU) / Санкт-Петербургский государственный университет (СПбГУ)
Russian Federation (RU)
How to cite
APA:
Rodionov, R.N., Oppici, E., Martens-Lobenhoffer, J., Jarzebska, N., Brilloff, S., Burdin, D.,... Bode-Boeger, S.M. (2016). A Novel Pathway for Metabolism of the Cardiovascular Risk Factor Homoarginine by alanine:glyoxylate aminotransferase 2. Scientific Reports, 6, 35277. https://doi.org/10.1038/srep35277
MLA:
Rodionov, Roman N., et al. "A Novel Pathway for Metabolism of the Cardiovascular Risk Factor Homoarginine by alanine:glyoxylate aminotransferase 2." Scientific Reports 6 (2016): 35277.
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