Glutamine is a
neutral amino acid that is electrophysiologically inert (1). Glutamine is by far the
most abundant free amino acid in plasma and tissues in humans and plays a number of important physiological roles
(2,3,4). In skeletal muscle
glutamine alone accounts for more than 60% of the free amino acid pool (5).
Glutamine is an important conditionally essential
amino acid with roles related with the immune
response to muscle damage, and is also utilized as an energy source by lymphocytes and macrophages (6). Glutamine is also
a component of cerebrospinal fluid,
intestinal mucose and imunne cells as an energy substrate, and also serves
as a nitrogen shuttle.
Plasma
concentrations are between 400 and 600 µmol/l. Tissue
concentrations vary between 2 and 20 mmol/l intracellular water (7). In
intracellular water of enterocytes glutamine concentrations range between 2 and
4 mmol/l (8). For muscle and liver the concentrations range between 5 and 20
mmol/l (7,9).
Most of the
glutamine synthesis occurs in skeletal muscle, which then gets released into plasma
at high rates. In skeletal muscle, glutamine helps buffer acids and build glycogen (10,11) and protein (12). However, glutamine
alone is no better than glucose alone at restoring muscle glycogen after glycogen-depleting exercise (11)
and adding glutamine to essential amino
acids and carbohydrate does not enhance muscle glycogen or protein synthesis
after glycogen depleting endurance exercise (13).
Glutamine can also increase
cell volume (14). Given the roles in immunity and anabolism, glutamine
was advanced, or shall we say promoted
as a vital supplement for endurance athletes (15,16) because plasma
glutamine levels tend to be decreased for a few hours after prolonged exercise.
L-glutamine supplementation can restore plasma
glutamine concentrations and improve systemic immune system function (17,18).
Although the data is overall weak, some research supports positive effects of
glutamine on immune function and the
prevention of upper respiratory tract infections (19,20,21). These possible
advantages explain in part the increase in popularity of glutamine
supplementation for strength and endurance athletes.
On the other hand, few studies support the
effectiveness on improving muscle function and reducing muscle soreness (22,23).
There is no compelling evidence to
support glutamine supplementation in terms of increasing lean body mass (24).
Clinical use of glutamine (Illness or trauma)
In diseased populations, or after trauma or surgery
there’s an increased amount of free
amino acids mobilized from skeletal muscle (25,26). A decrease in free
glutamine concentration in skeletal muscle is very indicative of whole body
protein catabolism (27,28,29). The same reduction in muscle glutamine is also
observed after 3 days of total
starvation (30).
Severe
illness results in wasting of muscle mass and when prolonged, muscle loss can
be extensive (31,32): a loss of lean body mass can occur after a few days of a
major burn (33,34); a loss of lean body mass exceeding 15% of total weight
results in a decrease in wound healing; a loss of 30% results in increased
infections, severe weakness, skin breakdown and no wound healing (35); and in
extreme cases 40% loss of lean body mass
resulting in death usually from
pneumonia (36).
An
inevitable loss of lean body mass between 10-15% or more can occur over several
weeks, but even though the cells are primed for anabolism after the injury or
disease is resolved (37), the rate of
lean mass gain or protein restoration is much slower than the loss (34,37).
(30)
Solid black line: control group, received no extra parenteral nutrition
support; Broken line: received a full course of Total Parenteral Nutrition that
began upon admission to the hospital 3 weeks after onset of the acute attack and
continued perioperatively until 14 days postoperation (37).
Nevertheless,
the release of amino acids from muscle during illness is considered essential for
recovery, wound healing, immune response and energy requirements (38), with the
two main amino acids released from muscle being alanine and glutamine (39). Alanine
is mainly used by the liver to form glucose and glutamine and is required for cellular
proliferation (40), fuel for the gut
and is important for maintaining gut
integrity from endotoxin translocation (41).
In severe
burn patients there’s alterations in
muscle glutamine transport with a significant increase in the
unidirectional transport of glutamine from muscle leading to a fall in muscle glutamine concentrations (36). There is
also accelerated production and release
of alanine. Pyruvate is transminated with glutamate to form alanine, and
glutamine is formed from glutamate and ammonia, thus the glutamate depletion to form alanine can limit the rate of glutamine
synthesis (42). Other measurements also show an increased net release of
glutamine from muscle, with reduced rates of glutamine transport and turnover
within muscle tissue (43).
These
changes in muscle glutamine metabolism could suggest a possible metabolic adaptation of muscle to
prolong depletion of glutamine; the decrease in the rate of glutamine synthesis
may limit further loss of muscle (44,45). On the other hand, healthy
individuals with glutamine availability show a reciprocal decrease in glutamine
production in muscle indicative of an appropriate feedback response to
increased glutamine availability (46).
Nevertheless,
in critical illness visceral
consumption of glutamine remains high as glutamine availability decreases
even though there’s an improved efficiency in glutamine transport out of muscle
(36,47).
Increases in intramuscular
sodium concentration, blood cortisol, adrenaline, glucagon, and decreases in plasma insulin, or
exposure to endotoxin could all result
in a decrease of intramuscular glutamine
concentration (48).
Parenteral vs. Enteral
The choice of feeding route results in different
metabolic handling of glutamine.
Parenteral
Positive effects from
glutamine on catabolism (anti-catabolism) are only seen when it is administered
via parenteral (intravenous) nutrition and in diseased
populations, after surgery (49) or in response to trauma, acute stress, infection, and burns (36,50).
The plasma response of
glutamine is more pronounced when parenterally
administered than when enterally administered (51). Anabolic effects of parenteral
glutamine feeding were seen in
experimental animals (52,53) and in humans (54,55).
Enteral
In one study when administered via the
enteral (oral) route glutamine was entirely metabolized in the splanchnic (gut) compartment and didn’t have a discernable effect on
whole-body protein and nitrogen kinetics (56). After a Ala-Gln dipeptide was enterally supplied a large
part of glutamine was probably metabolised in the splanchnic area (51).
The glutamine in circulation is taken up by the small
intestine (57,58), specially by the
mucosa which uses glutamine as a substrate for energy production even in the
presence of glucose (59). The total
splanchnic use of enterally supplied glutamine is likely to represent 50–70% of
glutamine ingestion (60,61), and is also used by the liver for gluconeogenesis in the fasted state.
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