Amino Acids

, Volume 47, Issue 9, pp 1703–1713 | Cite as

Homoarginine in the renal and cardiovascular systems

  • Stefan PilzEmail author
  • Andreas Meinitzer
  • Martin Gaksch
  • Martin Grübler
  • Nicolas Verheyen
  • Christiane Drechsler
  • Bríain ó Hartaigh
  • Florian Lang
  • Ioana Alesutan
  • Jakob Voelkl
  • Winfried März
  • Andreas Tomaschitz
Review Article
Part of the following topical collections:
  1. Homoarginine, Arginine and Relatives


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.


Homoarginine AGAT Cardiovascular Stroke Heart failure Nitric oxide Mortality 



Asymmetric dimethylarginine


l-Arginine:glycine amidinotransferase


AMP-activated protein kinase




Body mass index


Chronic kidney disease-mineral and bone disease


Guanidinoacetate N-methyltransferase


Glomerular filtration rate


Genome wide association study






Ludwigshafen risk and cardiovascular health


Major adverse cardiovascular events


Nitric oxide


Peripheral arterial disease


Protein arginine methyltransferase


Standard deviation


Single-nucleotide polymorphism




Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All studies reported here were approved by the local Ethics Committees.


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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Stefan Pilz
    • 1
    • 2
    Email author
  • Andreas Meinitzer
    • 3
  • Martin Gaksch
    • 1
  • Martin Grübler
    • 4
  • Nicolas Verheyen
    • 4
  • Christiane Drechsler
    • 5
  • Bríain ó Hartaigh
    • 6
  • Florian Lang
    • 7
  • Ioana Alesutan
    • 7
  • Jakob Voelkl
    • 7
  • Winfried März
    • 3
    • 8
  • Andreas Tomaschitz
    • 4
    • 9
    • 10
  1. 1.Division of Endocrinology and Metabolism, Department of Internal MedicineMedical University of GrazGrazAustria
  2. 2.Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care ResearchVU University Medical CentreAmsterdamThe Netherlands
  3. 3.Clinical Institute of Medical and Chemical Laboratory DiagnosticsMedical University of GrazGrazAustria
  4. 4.Department of CardiologyMedical University of GrazGrazAustria
  5. 5.Division of Nephrology, Department of Medicine IUniversity of WürzburgWürzburgGermany
  6. 6.Department of Radiology, Dalio Institute of Cardiovascular ImagingNewYork-Presbyterian Hospital and the Weill Cornell Medical CollegeNew YorkUSA
  7. 7.Department of PhysiologyUniversity of TübingenTübingenGermany
  8. 8.Synlab AcademySynlab Services GmbHMannheimGermany
  9. 9.Specialist Clinic for Rehabilitation Bad AusseeBad AusseeAustria
  10. 10.Department of Cardiology, Campus VirchowCharité UniversityBerlinGermany

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