Newly-revealed amino acid function could be used to
boost antioxidant levels
December 14, 2016
A Japanese research team has become the first in the world
to discover that 2-aminobutyric acid (2-AB) is closely involved in the
metabolic regulation of the antioxidant glutathione, and that it can
effectively raise levels of glutathione in the body when ingested.
Newly-revealed amino acid function
could be used to boost antioxidant levels.
Credit: Image courtesy of Kobe
A Japanese research team has become
the first in the world to discover that 2-aminobutyric acid (2-AB) is closely
involved in the metabolic regulation of the antioxidant glutathione, and that
it can effectively raise levels of glutathione in the body when ingested. The
findings were published in the online version of Scientific Reports on
Glutathione, an antioxidant with
antidotal properties, plays an important role in keeping us healthy. This
finding could contribute to the development of new ways to prevent, diagnose
and treat various oxidative stress-related conditions including Alzheimer’s,
aging, cancer, lifestyle-related diseases, hardened arteries, and organ damage
caused by medicines and toxins.
The team was led by Kobe University
Graduate School of Medicine, Division of Evidence-Based Laboratory Medicine
Assistant Professor IRINO Yasuhiro and Associate Professor TOH Ryuji, in
collaboration with Professor HIRATA Ken-ichi (Kobe University, Division of
Cardiovascular Medicine) and Professor MIYATA Okiko (Kobe Pharmaceutical
University, Medicinal Chemistry Laboratory)
Glutathione is a major antioxidant
component within cells, and keeps our bodies healthy by contributing to the
detoxification of foreign substances. Monitoring glutathione metabolism in the
body can help with early diagnosis of illness, as glutathione is consumed when
bodies experience oxidative stress. However, glutathione concentration in the
blood is 100- to 1000-fold lower than levels within cells, making it hard to
accurately measure. Our bodies also compensate for the depletion of glutathione
under stress, so circulating levels will not necessarily decrease during
illness. This makes it difficult to accurately monitor the metabolism of
glutathione just by measuring its levels in the blood.
Increasing levels of glutathione in
the body could help to prevent and treat a variety of conditions which involve
oxidative stress and organ damage caused by toxins. However, simply ingesting
glutathione does not efficiently increase glutathione levels in the body.
2-aminobutyric acid (2-AB) has been
reported as a basic component of ophthalmic acid, which is produced when
glutathione is synthesized. Until now, the metabolism and physiological effects
of 2-AB itself were unknown. The group investigated whether 2-AB could be a
marker for glutathione dynamics, and whether it could be used to modulate
Searching for leads to develop new
diagnoses and treatment to combat heart failure, the group started by
comprehensively analyzing metabolites in the bloodstreams of atrial septal
defect patients using a gas chromatography mass spectrometer. Results showed
that levels of 2-AB were higher in these patients than in healthy subjects, and
2-AB levels decreased after the closure of atrial septal defect. Then, the
group clarified for the first time that 2-AB is a byproduct of cysteine, one of
the constituent amino acids of glutathione, and revealed that activation of
glutathione synthetic pathway under oxidative damage led to 2-AB accumulation.
Because blood concentration of 2-AB reflects the metabolism of glutathione
within the body, 2-AB could potentially be used as a new biomarker for early
detection of oxidative stress.
Intriguingly, the group also found
that 2-AB promotes glutathione synthesis. The anticancer drug doxorubicin
causes heart damage via oxidative stress as an adverse effect. They discovered
that when taken orally, 2-AB increases the concentration of glutathione in the
bloodstream and the heart, lessening the heart damage caused by doxorubicin.
This research found that as well as
being a biomarker, 2-AB itself is an antioxidant that can be used to
effectively increase glutathione in the body (patent pending). 2-AB is a
naturally-occurring amino acid that can be found in everyday food products. Future
research will examine which foods contain high levels of 2-AB, the recommended
level to ingest, whether it can be used as an antioxidant for other organs, and
the development of medicines and functional food for clinical use.
Materials provided by Kobe
University. Note: Content may be edited for style and length.
- Yasuhiro Irino, Ryuji Toh, Manabu Nagao, Takeshige
Mori, Tomoyuki Honjo, Masakazu Shinohara, Shigeyasu Tsuda, Hideto
Nakajima, Seimi Satomi-Kobayashi, Toshiro Shinke, Hidekazu Tanaka, Tatsuro
Ishida, Okiko Miyata, Ken-ichi Hirata. 2-Aminobutyric acid modulates
glutathione homeostasis in the myocardium. Scientific Reports,
2016; 6: 36749 DOI: 10.1038/srep36749
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