Homoarginine in the renal and cardiovascular systems.
Homoarginine (hArg) is an endogenous, nonproteinogenic amino acid which differs from arginine by an additional methylene (CH2) group in the backbone. In this brief narrative review, we summarize the current literature on hArg in the renal and cardiovascular systems. Epidemiological studies have identified low hArg levels as an independent risk marker for cardiovascular, cerebrovascular, and renal diseases as well as for mortality. The relatively low correlation of hArg with established cardiovascular risk factors underlines its great potential as an emerging biomarker to improve risk prediction because plasma hArg concentrations might reflect previously unrecognized pathophysiological processes. hArg may be involved in the pathogenesis of various diseases due to its effects on nitric oxide (NO) and energy metabolism. In view of its structural similarities with arginine, it has been proposed that hArg impacts on arginine metabolism and subsequently also on NO synthesis. The key enzyme for hArg synthesis, arginine:glycine amidinotransferase (AGAT), is involved in the synthesis of energy metabolites including guanidinoacetate, the precursor of creatine. Therefore, the involvement of hArg in energy metabolism could partially explain the close association between hArg and cardiovascular diseases such as heart failure. Whether hArg supplementation or modification of key enzymes of hArg metabolism such as AGAT activity is effective for the treatment of chronic diseases remains to be elucidated.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria, stefan.pilz@chello.at.
Stefan
S
Pilz
Andreas
A
Meinitzer
Martin
M
Gaksch
Martin
M
Grübler
Nicolas
N
Verheyen
Christiane
C
Drechsler
Bríain Ó
BÓ
Hartaigh
Florian
F
Lang
Ioana
I
Alesutan
Jakob
J
Voelkl
Winfried
W
März
Andreas
A
Tomaschitz
D000579:Amidinotransferases / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002561:Cerebrovascular Disorders / Q000097:blood* / Q000401:mortality; D004734:Energy Metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000097:blood; D006333:Heart Failure / Q000097:blood* / Q000401:mortality; D006709:Homoarginine / Q000097:blood*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000401:mortality; D009569:Nitric Oxide / Q000097:blood
D015415:Biomarkers; D006709:Homoarginine; D009569:Nitric Oxide; D000579:Amidinotransferases; C020681:glycine amidinotransferase; C004946:glycocyamine; D005998:Glycine