Biomedical Engineering Reference
In-Depth Information
INTRODUCTION
Arginine (Arg) was i rst isolated and named in 1886. Its presence in animal
protein was documented in 1895. Arg was classii ed as a semi-essential amino
acid at er a study by Rose (1937) observed that adult rats did not require dietary
Arg for growth and maintenance of nitrogen balance, but that young growing
rats demonstrated more rapid growth when receiving dietary Arg. h is i nding
indicated that endogenous biosynthesis of Arg occurs but not at a sui cient rate
for maximal growth in the young. h is was also found to be true for humans. Arg
has been shown to possess numerous physiological properties. It functions in the
body as a free amino acid, a component of most proteins, and as a substrate for
several non-protein, nitrogen-containing compounds. As a free amino acid, Arg is
an integral constituent of the urea cycle. Arg contains a guanidine group, which is
essential for the synthesis of urea in most mammals. In the cytosol of hepatocytes,
arginase removes the guanidine group from Arg to produce urea and ornithine.
Urea is then transported from the hepatocyte into the blood, and ornithin is used
to regenerate Arg within hepatocytes. Another function of Arg is protein synthesis.
Arg can be converted into proline, glutamate, and glutamine, all of which are
common amino acids found within most proteins. Arg metabolism also generates
several essential non-protein and nitrogen-containing compounds, including
creatine, polyamines, and nitric oxide (NO). Synthesis of creatine is dependent
on the guanidine group of Arg. Creatine functions as a carrier for phosphate
and is needed for the rapid regeneration of adenosine triphosphate in muscles.
Polyamines function in membrane transport and in cell growth, proliferation, and
dif erentiation. Arg and products of Arg metabolism are necessary for both the
regulation and synthesis of polyamine. Arg not only provides the substrate for
polyamine synthesis, it also indirectly stimulates the release of growth hormone,
which in turn promotes polyamine synthesis by increasing ornithine decarboxylase
activity. Arg is a precursor of NO. NO, a short-lived small molecule produced
by most cell types, has a variety of well-dei ned pathophysiological roles. NO is
an antimicrobial agent that is ef ective against pathogens, parasites, and bacteria.
NO is also a neurotransmitter and vasodilator. h e enzyme that produces NO
is nitric oxide synthase (NOS). h ere are three isoforms of NOS. NOS-1 (also
known as nNOS) is constitutive and is predominantly located in neuronal tissue.
NOS-2 (iNOS) is inducible and is located in a variety of tissues. NOS-3 (eNOS) is
constitutive and is primarily localized in endothelial tissue.
ARGININE AND IMMUNITY
Previous reports showed that plasma Arg declines at er severe injury, and a marked
reduction in serum Arg is a predictor of mortality in septic patients (Freund
et al.
1979). Arg supplementation signii cantly increases plasma Arg levels. Numerous
studies have demonstrated the benei ts of Arg supplementation on immune
