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Homoarginine in the renal and cardiovascular systems

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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.

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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

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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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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria

    Stefan Pilz & Martin Gaksch

  2. Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands

    Stefan Pilz

  3. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria

    Andreas Meinitzer & Winfried März

  4. Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria

    Martin Grübler, Nicolas Verheyen & Andreas Tomaschitz

  5. Division of Nephrology, Department of Medicine I, University of Würzburg, Oberdürbacherstrasse 6, 97080, Würzburg, Germany

    Christiane Drechsler

  6. Department of Radiology, Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital and the Weill Cornell Medical College, 507 E 61st Street, New York, USA

    Bríain ó Hartaigh

  7. Department of Physiology, University of Tübingen, Gmelinstrasse 5, 72076, Tübingen, Germany

    Florian Lang, Ioana Alesutan & Jakob Voelkl

  8. Synlab Academy, Synlab Services GmbH, Gottlieb-Daimler Strasse 25, 68165, Mannheim, Germany

    Winfried März

  9. Specialist Clinic for Rehabilitation Bad Aussee, Braungasse 354, 8990, Bad Aussee, Austria

    Andreas Tomaschitz

  10. Department of Cardiology, Campus Virchow, Charité University, Berlin, Germany

    Andreas Tomaschitz

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  1. Stefan Pilz
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  2. Andreas Meinitzer
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  7. Bríain ó Hartaigh
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  8. Florian Lang
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  11. Winfried März
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  12. Andreas Tomaschitz
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Correspondence to Stefan Pilz.

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Pilz, S., Meinitzer, A., Gaksch, M. et al. Homoarginine in the renal and cardiovascular systems. Amino Acids 47, 1703–1713 (2015). https://doi.org/10.1007/s00726-015-1993-2

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  • DOI: https://doi.org/10.1007/s00726-015-1993-2

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