The Second Life of Methylarginines as Cardiovascular Targets.
6-guanidino-2-oxocaproic acid (GOCA)
Homoarginine
alanine:glyoxylate aminotransferase 2 (AGXT2)
asymmetric dimethylarginine (ADMA)
asymmetric α-keto-dimethylguanidinovaleric acid (ADGV)
beta-aminoisobutyric acid (BAIBA)
dimethylarginine dimethylaminohydrolase (DDAH)
symmetric dimethylarginine (SDMA)
symmetric α-keto-dimethylguanidinovaleric acid (SDGV)
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
17 Sep 2019
17 Sep 2019
Historique:
received:
14
08
2019
revised:
13
09
2019
accepted:
15
09
2019
entrez:
20
9
2019
pubmed:
20
9
2019
medline:
6
2
2020
Statut:
epublish
Résumé
Endogenous methylarginines were proposed as cardiovascular risk factors more than two decades ago, however, so far, this knowledge has not led to the development of novel therapeutic approaches. The initial studies were primarily focused on the endogenous inhibitors of nitric oxide synthases asymmetric dimethylarginine (ADMA) and monomethylarginine (MMA) and the main enzyme regulating their clearance dimethylarginine dimethylaminohydrolase 1 (DDAH1). To date, all the screens for DDAH1 activators performed with the purified recombinant DDAH1 enzyme have not yielded any promising hits, which is probably the main reason why interest towards this research field has started to fade. The relative contribution of the second DDAH isoenzyme DDAH2 towards ADMA and MMA clearance is still a matter of controversy. ADMA, MMA and symmetric dimethylarginine (SDMA) are also metabolized by alanine: glyoxylate aminotransferase 2 (AGXT2), however, in addition to methylarginines, this enzyme also has several cardiovascular protective substrates, so the net effect of possible therapeutic targeting of AGXT2 is currently unclear. Recent studies on regulation and functions of the enzymes metabolizing methylarginines have given a second life to this research direction. Our review discusses the latest discoveries and controversies in the field and proposes novel directions for targeting methylarginines in clinical settings.
Identifiants
pubmed: 31533264
pii: ijms20184592
doi: 10.3390/ijms20184592
pmc: PMC6769906
pii:
doi:
Substances chimiques
Biomarkers
0
symmetric dimethylarginine
49787G1ULV
N,N-dimethylarginine
63CV1GEK3Y
Arginine
94ZLA3W45F
Amidohydrolases
EC 3.5.-
dimethylargininase
EC 3.5.3.18
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
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