L-homoarginine and cardiovascular disease

Curr Opin Clin Nutr Metab Care. 2015 Jan;18(1):83-8. doi: 10.1097/MCO.0000000000000123.

Abstract

Purpose of review: An increasing number of reports indicate that low levels of the endogenous amino acid L-homoarginine are linked to cardiovascular disease. In this article, we review the current findings regarding L-homoarginine metabolism and (patho-)physiology with a focus on its clinical impact.

Recent findings: Recent clinical and epidemiological studies revealed a strong association of low circulating L-homoarginine with cardiovascular outcomes and mortality. Human and murine studies identified L-arginine:glycine amidinotransferase (AGAT) as the responsible enzyme for endogenous L-homoarginine formation, suggesting a further important function of AGAT apart from its involvement in creatine and energy metabolism. Further studies related L-homoarginine to smoking and hypertension, and metabolic phenotypes.

Summary: AGAT deficiency results in diminished intracellular energy stores (i.e., ATP and phosphocreatine), as well as a lack of L-homoarginine, and has been linked to an improved metabolic risk profile, but also to impaired cardiac and cerebrovascular function. L-homoarginine's structural similarity to L-arginine suggested physiological interference with L-arginine pathways (e.g., nitric oxide). Animal experiments and clinical trials are needed to improve knowledge on the physiology of L-homoarginine and differentiate its role as marker and mediator in cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amidinotransferases / deficiency*
  • Amino Acid Metabolism, Inborn Errors / complications*
  • Animals
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / metabolism
  • Developmental Disabilities / complications
  • Energy Metabolism
  • Homoarginine / deficiency*
  • Homoarginine / metabolism
  • Humans
  • Intellectual Disability / complications*
  • Speech Disorders / complications*

Substances

  • Homoarginine
  • Amidinotransferases

Supplementary concepts

  • Arginine-Glycine Amidinotransferase Deficiency