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Amino Acids

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

Homoarginine in the renal and cardiovascular systems

  • Stefan Pilz
  • 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

Abstract

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.

Keywords

Homoarginine AGAT Cardiovascular Stroke Heart failure Nitric oxide Mortality 

Abbreviations

ADMA

Asymmetric dimethylarginine

AGAT

l-Arginine:glycine amidinotransferase

AMPK

AMP-activated protein kinase

Arg

l-Arginine

BMI

Body mass index

CKD-MBD

Chronic kidney disease-mineral and bone disease

GAMT

Guanidinoacetate N-methyltransferase

GFR

Glomerular filtration rate

GWAS

Genome wide association study

hArg

l-Homoarginine

KO

Knockout

LURIC

Ludwigshafen risk and cardiovascular health

MACE

Major adverse cardiovascular events

NO

Nitric oxide

PAD

Peripheral arterial disease

PRMT

Protein arginine methyltransferase

SD

Standard deviation

SNP

Single-nucleotide polymorphism

WT

Wild-type

Notes

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
  • 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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