Role of Glutamine as an Ergogenic Amino Acid during Fatigue

Abstract

Physical activity has an impact on the interior environment's balance. Contracting muscles provide force, power, and heat during exercise. As a result, physical activity is a kind of mechanical energy. The body's energy reserves will be depleted as a result of the created energy. During exercise, metabolites and heat are produced, affecting the internal environment's steady state. Depending on the type of activity, weariness and exhaustion will set in sooner or later. Glutamine is the most common free amino acid in human muscle and plasma, and it is used extensively by rapidly proliferating cells, such as leucocytes, to supply energy and ideal circumstances for nucleotide production. As a result, it is thought to be necessary for effective immunological function. Glutamate serves a variety of functions, including protein synthesis, an anabolic precursor for muscle growth, acid-base balance in the kidney, ureagenesis in the liver, hepatic and renal gluconeogenesis, oxidative fuel for the intestine and immune system cells, inter-organ nitrogen transport, a precursor for neurotransmitter synthesis, a precursor for nucleotide and nucleic acid synthesis, and precursor for glutathione production. Severe metabolic stress, such as sepsis or extensive surgery, depletes glutamine reserves in muscles. As a result, it is regarded as conditionally vital in certain circumstances. The physiological importance of glutamine is discussed in this review, as well as how glutamine supplementation can help with weariness.

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Role of Glutamine as an Ergogenic Amino Acid during Fatigue
Keshav Trivedi1, Md Sadique Hussain2,*, Chandan Mohapatra2
1School of Engineering and Technology, Jaipur National University, Jagatpura (302017), Jaipur, Rajasthan, India.
2School of Pharmaceutical Sciences, Jaipur National University, Jagatpura (302017), Jaipur, Rajasthan, India.
Corresponding Author: Sadique Hussain, School of Pharmaceutical Sciences, Jaipur National University Jagatpura (302017), Jaipur,
Rajasthan, India.
Received Date: November 01, 2021; Accepted Date: December 16, 2021; Published Date: January 05, 2022
Citation: Keshav Trivedi, Md Sadique Hussain, Chandan Mohapatra (2022) Role of Glutamine as an Ergogenic Amino Acid during
Fatigue, J, Clinical Medical Reviews and Reports. 4(2); DOI:10.31579/2690-8794/111
Copyright: © 2022, Sadique Hussain, This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Physical activity has an impact on the interior environment's balance. Contracting muscles provide force, power, and
heat during exercise. As a result, physical activity is a kind of mechanical energy. The body's energy reserves will be
depleted as a result of the created energy. During exercise, metabolites and heat are produced, affecting the internal
environment's steady state. Depending on the type of activity, weariness and exhaustion will set in sooner or later.
Glutamine is the most common free amino acid in human muscle and plasma, and it is used extensively by rapidly
proliferating cells, such as leucocytes, to supply energy and ideal circumstances for nucleotide production. As a result,
it is thought to be necessary for effective immunological function. Glutamate serves a variety of functions, including
protein synthesis, an anabolic precursor for muscle growth, acid-base balance in the kidney, ureagenesis in the liver,
hepatic and renal gluconeogenesis, oxidative fuel for the intestine and immune system cells, inter-organ nitrogen
transport, a precursor for neurotransmitter synthesis, a precursor for nucleotide and nucleic acid synthesis, and precursor
for glutathione production. Severe metabolic stress, such as sepsis or extensive surgery, depletes glutamine reserves in
muscles. As a result, it is regarded as conditionally vital in certain circumstances. The physiological importance of
glutamine is discussed in this review, as well as how glutamine supplementation can help with weariness.
Keywords: anti-fatigue, immune booster, exercise enhancer, muscle repair
Introduction
Many physiologists have been interested in exercise-induced weariness
and exhaustion for far more than a century. Even though most exercise-
related research focuses on the neuromuscular system, all organs are
involved. Other organs, in addition to the neuromuscular system, respond
to an individual's exercise ability. This exercise ability is widely
recognized to be diminished during sickness. End-stage renal failure, for
example, has a significant influence on exercise ability [1, 2]. Fatigue is
the inability to maintain power production and strength, resulting in a
reduction in physical performance. The buildup of protons in the muscle
cell, depletion of energy supplies (e.g., phosphocreatine and glycogen),
ammonia accumulation in the blood and tissues, oxidative stress, muscle
injury, and changes in neurotransmitter production, such as an increase in
serotonin and a reduction in dopamine, are the major causes of weariness.
Several dietary techniques have been used to postpone the onset of
weariness and increase athletic performance. The role of amino acids in
the improvement of fatigue has been debated since the mid-1980s and
1990s, and indication has shown that plasma glutamine concentrations
and the glutamine/glutamate plasma ratio are diminished in athletes
suffering from chronic fatigue and overtraining syndrome, raising the
question of glutamine supplementation's possible ergogenic effects [3, 4].
Of the 20 amino acids in humans, glutamine (Gln) is the most prevalent
free (non-essential) amino acid. In healthy people, no deficits are expected
to exist because Gln can be produced from scratch [5] Figure 1 shows the
steps in the synthesis of Gln. It also functions as a precursor of nucleotide
bases and the antioxidant glutathione in acid-base control,
gluconeogenesis, and as a precursor of nucleotide bases and glutathione
[6, 7]. Gln levels drop dramatically in a variety of catabolic illness
conditions, prompting speculation that Gln is a conditionally required
dietary component rather than a non-essential amino acid [8]. During
acute metabolic stress, such as sepsis or major surgery, Gln is drained
from muscle reserves. As a result, it is regarded conditionally necessary
under certain circumstances [9]. During a short-term fast, such as an
overnight fast, Gln is the major amino acid produced from skeletal
muscle. The concentration of Gln in human muscle is 20 mmol/L,
compared to 0.6 mmol/L in plasma. During times of stress, such as
exercise, a rise in cortisol levels in the blood causes muscle protein
proteolysis and Gln release. The liver, muscle, adipose, and lung are
among the tissues that may produce and release Gln into the circulation.
However, skeletal muscle is the most significant, since it both synthesizes
and stores Gln, which is absorbed by the colon, liver, and kidney, as well
as some immune system cells. The whole human muscle releases about
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8–9g of Gln each day [10]. Gln is the most common amino acid in the
human body and is involved in the prevention and treatment of
physiological stress and serious disease on a biological level. Gln
supplementation has been linked to improvements in biological indicators
of heat stress in both human and animal models, as well as a reduction in
athletes' perceived weariness [11].
Figure 1: Synthesis of Glutamine.
The enzyme Gln synthetase (GS) is primarily responsible for the
production of Gln, which is then hydrolyzed by glutaminase (GLS). Gln
biosynthesis is catalysed by GS utilising glutamate and ammonia (NH3)
as sources. One ATP is spent in this reaction. Many amino acids can
supply glutamate, either exogenously (via the food) or endogenously
(through the degradation of endogenous amino acids). GLS, on the other
hand, is in charge of converting glutamine to glutamate and ammonium
ion (NH4). GS and GLS are expressed by almost all cells in the body, and
their predominant expression and activity determine whether a tissue is
more likely to create or consume Gln in health and sickness [12].
Athletes have an increased risk of sickness following extensive,
exhausting activity, as has been widely established. Individuals who have
completed a marathon, for example, have greater symptoms than athletes
who engage in moderate activity or athletes who prepare for but do not
compete in endurance events. Furthermore, additional evidence has been
gathered indicating Gln's putative significance in the immune system.
When compared to the number of infections reported by athletes
following a 15-mile training session or a 10-kilometer race, infections
were higher in most categories of athletes tested after an intensive training
session or an endurance event. Gln in a drink reduced the frequency of
infections in athletes during the week after various forms of exhausting,
long-duration exercise [13] Figure 2 represents the other broader
functions of glutamine.
Figure 2: General functions of glutamine.

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Glutamine as Anti-Fatigue
Gln quantities in the body are not only high but also exceedingly labile,
as scientists discovered a few years ago. The concentration of Gln in the
circulation and cellular pools drops rapidly after surgery, damage,
systemic infection, and other serious disorders. The drop in Gln
concentrations is bigger than any other amino acid, correlates to the
severity of the underlying illness process in general, and is only restored
late in the healing phase. The fast loss of large amounts of Gln from
muscle pools in catabolic illness shows that Gln may make up a
considerable portion of the labile protein pool recruited after damage [14,
15]. It's been suggested that a lack of Gln in the muscles might lead to a
slower rate of lymphocyte proliferation in response to antigens,
compromising immunological protection against viral infection. Intense
physical activity may reduce the rate of Gln production from skeletal
muscle and/or accelerate the amount of Gln absorption by other Gln-using
organs or tissues, reducing Gln availability for immune system cells [16,
17]. In figure 3, it represents the mechanism of glutamine as an anti-
fatigue.
Figure 3: Schematic diagram of the mechanism of action of glutamine as an anti-fatigue ergogenic amino acid.
Gln has also been linked to the avoidance of ammonia buildup. Ammonia
is produced during exercise as a result of amino acid oxidation and energy
metabolism, implying a decrease in ATP concentration and glycogen
content; consequently, Gln supplementation may reduce ammonia
generation by affecting energy metabolism. Because ammonia is
poisonous and impairs the activity of several flux-generating enzymes,
cell permeability to ions, and the ratio of NAD+/NADH, ammonia
buildup is a major cause of tiredness [18]. Finally, Gln may help to avoid
dehydration, which is a potential anti-fatigue effect. A sodium-dependent
mechanism transports Gln over the intestinal brush barrier, facilitating
greater Gln absorption [19, 20]. Given its possible benefits, Gln appears
to be a promising supplement for reducing tiredness, particularly for
athletes who participate in endurance sports [21]. In Figure 4, the primary
features of glutamine in postponing tiredness are shown.

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Figure 4: Anti-fatigue properties of Glutamine.
Glutamine Supplements and Muscle Anabolic
Processes
In a fasting condition, muscle protein is broken down. A recent study
suggests that resistance training lowers protein catabolism, but an
anabolic (muscle growth) response needs the consumption of necessary
amino acids (dietary protein) during the recovery period following
exercise. This improves the rate of tissue protein synthesis without
influencing the rate of protein breakdown by increasing amino acid
absorption into the muscle. Taking supplements of specific non-essential
amino acids at this time is unlikely to give any further benefit if the
consumed protein contains the 8 necessary amino acids [22].
Serial
No.
Changes in the muscle fibers
1
Pi (inorganic phosphate) accumulates in the sarcoplasm, resulting in a reduction in contractile force owing to the
suppression of cross-bridge contacts.
2
H+ ion accumulation in the sarcoplasm, which results in a reduction in contractile force owing to suppression of
cross-bridge interactions. Furthermore, an increase in H+ ions in the sarcoplasmic reticulum may induce a decrease
in calcium re-uptake. This might be the major reason for the increased relaxing period following fatiguing
contractions.
3
Mg2+ ions accumulate in the sarcoplasm. The release of Ca2+ from the sarcoplasmic reticulum is inhibited by
Mg2+.
4
Pi buildup inhibits the sarcoplasmic reticulum's release of Ca2+. Precipitation of calcium phosphate inside the
sarcoplasmic reticulum lumen and phosphorylation of the Ca2+ release channels both impede Ca2+ release.
5
Glycogen reserves are depleting, and blood glucose levels are dropping (in severe situations). Even a brief drop in
blood glucose can have a significant impact on CNS processes. Increased muscular fatigue is caused by the depletion
of glycogen reserves in an unknown way.

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6
Reduced action potential conduction velocity along the sarcolemma, most likely as a result of exercise-related
metabolic changes in and around muscle fibers. The decrease in conduction velocity is mirrored in the EMG (change
in frequency content), but no immediate effect on muscle force output is recognized.
7
Potassium ions (K+) outflow from muscle fibers is increased. Because of the depression of excitation-contraction
coupling, an increase in potassium in the t-tubule lumen may result in a block of the tubular action potential and
hence reduced force.
8
Neuromuscular synaptic transmission can be impeded; however, this appears to be a disease-related component
(myasthenia gravis).
Table 1: Overview of exercise-related changes that can occur in the muscle fibers [23, 24].
There's some evidence that Gln supplementation can help promote
glycogen synthesis in the first few hours following a workout: Ingesting
8g of Gln along with 61g of glucose polymer after a glycogen-depleting
bout of exercise resulted in a 25% increase in whole-body glucose
disposal in the 2 hours following the exercise, compared to glucose
polymer alone. However, a further study including appropriate
carbohydrate eating after exercise is needed to back up this conclusion
and provide it practical application [25]. The amount of carbohydrate
consumed is insufficient; more than 100g is required to reach the maximal
rate of muscle glycogen synthesis throughout a 2-hour post-exercise
interval. As a result, a post-workout meal that is primarily carbohydrate
(100g) with some protein (20g) appears to be the optimal strategy for
promoting both glycogen and protein synthesis in muscle. The plasma
content of growth hormone was boosted 4-fold 90 minutes after oral
administration of 2g Gln, according to one research. However, because 1
hour of moderate to high-intensity activity can result in a 20-fold rise in
plasma growth hormone concentration, Gln supplements are not
recommended for athletes who exercise [26, 27]. Plasma Gln
concentrations are unaffected by eccentric exercise-induced muscle
injury. There is no empirical evidence that oral Gln supplementation
improves muscle regeneration following exercise-induced injury, and
there is no evidence that Gln consumption reduces muscular soreness
when compared to placebo [28, 29].
Glutamine Intakes in the Athletic Population
Gln intake through dietary protein is typically 3–6 g/d (assuming a daily
protein consumption of 0.8–1.6 g/kg bm for a 70-kg person). L-glutamine
pills or capsules (250, 500, and 1000 mg) or powder are now available as
supplements. Protein supplements, such as whey protein and protein
hydrolysates, are other dietary sources of Gln for athletes. Although Gln
is regarded to be quite safe and well accepted by most individuals, it is
not indicated for persons with renal issues. In healthy athletes, no adverse
effects to short-term Gln supplementation of 20–30 g within a few hours
have been documented [30, 31].
Although there is little research on Gln supplement in the athletic
population in terms of strength and performance, it seems logical to
conclude that it may be useful for those who engage in prolonged and
rigorous exercise training. The amount of glutamine in muscle decreases
in proportion to the amount of stress. Furthermore, during and after
intense training, plasma glutamine levels drop. Furthermore, under
stressful conditions, the quantity of glutamine produced by skeletal
muscle is larger than the amount detected in the intracellular pool and
incorporated into proteins. Glutamate, on the other hand, may promote
skeletal muscle hydration, increasing cellular volume. Increased cell
volume might be an anabolic signal for muscle cells, resulting in increased
muscular strength [32-34].
Conclusion
It is now well understood that Gln is used extensively by a vast variety of
bodily tissues and cells and that it is required for their proper function.
Kidney, gut, liver, certain neurons in the CNS, immune system cells, and
pancreatic β-cells are among these tissues and cells. Because quick
workout, nutrient intake, disease, and traumatic injury all affect plasma
Gln levels, researchers should be aware of these influences and consider
it if they plan to use plasma Gln measurement as part of a series of tests
to oversee athletes for indications of impending overtraining. The usage
of Gln as a dietary supplement by athletes has ergogenic effects. Athletes
that participate in strength-power exercises, which need a substantial
amount of skeletal muscle mass, would benefit from the Gln. In all
athletes, glutamine may help to mitigate the immune system's impacts of
overtraining.
Conflict of Interest
None.
Funding
None.
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