Glutamine
Encyclopedia
Glutamine is one of the 20 amino acid
s encoded by the standard genetic code
. It is not recognized as an essential amino acid
but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders. Its side-chain is an amide
formed by replacing the side-chain hydroxyl
of glutamic acid
with an amine
functional group
. Therefore, it can be considered the amide of glutamic acid
. Its codons
are CAA and CAG. In human blood, glutamine is the most abundant free amino acid
, with a concentration of about 500-900 µmol/l.
glutamine synthetase
from glutamate and ammonia. The most relevant glutamine-producing tissue is the muscle mass, accounting for about 90% of all glutamine synthesized. Glutamine is also released, in small amounts, by the lung and the brain. Although the liver is capable of relevant glutamine synthesis, its role in glutamine metabolism is more regulatory than producing, since the liver takes up large amounts of glutamine derived from the gut.
cells. In respect to the last point mentioned, different glutamine analogues such as DON
, Azaserine
or Acivicin
are tested as anti-cancer drugs.
, bodybuilding
, endurance, and other sports. Evidence indicates that glutamine when orally loaded may increase plasma HGH levels by stimulating the anterior pituitary gland. In biological research, L-glutamine is commonly added to the media in cell culture
.
time after operations. Hospital-stay times after abdominal surgery
can be reduced by providing parenteral nutrition regimes containing high amounts of glutamine to patients. Clinical trials have revealed that patients on supplementation regimes containing glutamine have improved nitrogen balances, generation of cysteinyl-leukotriene
s from polymorphonuclear neutrophil granulocytes, and improved lymphocyte
recovery and intestinal permeability (in postoperative patients), in comparison to those that had no glutamine within their dietary regime, all without any side-effects
.
in the human body and one of the few amino acids that directly cross the blood-brain barrier
. In the body, it is found circulating in the blood as well as stored in the skeletal muscle
s. It becomes conditionally essential (requiring intake from food or supplements) in states of illness or injury.
. Small amounts of free L-glutamine are also found in vegetable juices and foods such as tofu.
function and cell differentiation.
This may relate to the fact that the intestinal extraction rate of glutamine is higher
than that for other amino acids, and is therefore thought to be the most viable option when attempting to alleviate conditions relating to the gastrointestinal tract.
These conditions were discovered within the gut between glutamine-enriched and non-glutamine-enriched diets. However, even though glutamine is thought to have "cleansing" properties and effects, it is unknown to what extent glutamine has clinical benefits, due to the varied concentrations of glutamine in varieties of food.
Glutamine may help to protect the lining of the gastrointestinal tract or mucosa. It has been suggested that people who have inflammatory bowel disease IBD (ulcerative colitis and Crohn' s disease) may not have enough glutamine. However, two clinical trials found that taking glutamine supplements did not improve symptoms of Crohn' s disease. More research is needed.
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s encoded by the standard genetic code
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
. It is not recognized as an essential amino acid
Essential amino acid
An essential amino acid or indispensable amino acid is an amino acid that cannot be synthesized de novo by the organism , and therefore must be supplied in the diet.-Essentiality vs. conditional essentiality in humans:...
but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders. Its side-chain is an amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
formed by replacing the side-chain hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
of glutamic acid
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
with an amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
. Therefore, it can be considered the amide of glutamic acid
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
. Its codons
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
are CAA and CAG. In human blood, glutamine is the most abundant free amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
, with a concentration of about 500-900 µmol/l.
Glutamine structure
Functions
Glutamine plays a role in a variety of biochemical functions including:- Protein synthesis, as any other amino acidAmino acidAmino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
. - Regulation of acid-base balance in the kidney by producing ammoniumAmmoniumThe ammonium cation is a positively charged polyatomic cation with the chemical formula NH. It is formed by the protonation of ammonia...
. - Cellular energy, as a source, next to glucoseGlucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
. - NitrogenNitrogenNitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
donation for many anabolic processesAnabolismAnabolism is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy. One way of categorizing metabolic processes, whether at the cellular, organ or organism level is as 'anabolic' or as 'catabolic', which is the opposite...
. - Carbon donation, as a source, refilling the citric acid cycleCitric acid cycleThe citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
. - Nontoxic transporter of ammonia in the blood circulation.
Producers
Glutamine is synthesized by the enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
glutamine synthetase
Glutamine synthetase
Glutamine synthetase is an enzyme that plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine:Glutamate + ATP + NH3 → Glutamine + ADP + phosphate...
from glutamate and ammonia. The most relevant glutamine-producing tissue is the muscle mass, accounting for about 90% of all glutamine synthesized. Glutamine is also released, in small amounts, by the lung and the brain. Although the liver is capable of relevant glutamine synthesis, its role in glutamine metabolism is more regulatory than producing, since the liver takes up large amounts of glutamine derived from the gut.
Consumers
The most eager consumers of glutamine are the cells of intestines, the kidney cells for the acid base balance, activated immune cells and many cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cells. In respect to the last point mentioned, different glutamine analogues such as DON
6-Diazo-5-oxo-L-norleucine
6-Diazo-5-oxo-L-norleucine is a glutamine antagonist, which was isolated originally from Streptomyces. It is a non-standard amino acid. The diazo compound was characterized in 1956 by Henry W Dion et al., who suggested a possible use in cancer therapy. This antitumoral efficacy was confirmed in...
, Azaserine
Azaserine
Azaserine is a carcinogen primarily used for researching pancreatic cancer in animal models. It is a glutamine analogue that irreversibly inhibits glutamine utilizing enzymes such as Gln: Phosphoribosyl Amidotransferase, which is involved in the biosynthesis of Inosine monophosphate...
or Acivicin
Acivicin
Acivicin is a glutamine analog antimetabolite, used as an antineoplasitc agent. It is fermented product of Streptomyces sviceus. It interferes with glutamate metabolism and inhibits glutamate dependent synthesis of enzymes, and is thereby potentially helpful in the treatment of solid...
are tested as anti-cancer drugs.
Examples for the usage of glutamine
In catabolic states of injury and illness, glutamine becomes conditionally-essential (requiring intake from food or supplements). Glutamine has been studied extensively over the past 10–15 years and has been shown to be useful in treatment of serious illnesses, injury, trauma, burns, and treatment-related side-effects of cancer as well as in wound healing for postoperative patients. Glutamine is also marketed as a supplement used for muscle growth in weightliftingPowerlifting
Powerlifting is a strength sport. It resembles the sport of Olympic weightlifting, as both disciplines involve lifting weights in three attempts. Powerlifting evolved from a sport known as 'odd lifts' which followed the same three attempt format but used a wide variety of events akin to Strongman...
, bodybuilding
Bodybuilding
Bodybuilding is a form of body modification involving intensive muscle hypertrophy. An individual who engages in this activity is referred to as a bodybuilder. In competitive and professional bodybuilding, bodybuilders display their physiques to a panel of judges, who assign points based on their...
, endurance, and other sports. Evidence indicates that glutamine when orally loaded may increase plasma HGH levels by stimulating the anterior pituitary gland. In biological research, L-glutamine is commonly added to the media in cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
.
Aiding recovery after surgery
It is also known that glutamine has various effects in reducing healingWound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
time after operations. Hospital-stay times after abdominal surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
can be reduced by providing parenteral nutrition regimes containing high amounts of glutamine to patients. Clinical trials have revealed that patients on supplementation regimes containing glutamine have improved nitrogen balances, generation of cysteinyl-leukotriene
Leukotriene
Leukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...
s from polymorphonuclear neutrophil granulocytes, and improved lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
recovery and intestinal permeability (in postoperative patients), in comparison to those that had no glutamine within their dietary regime, all without any side-effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
.
Occurrences in nature
Glutamine is the most abundant naturally occurring, non-essential amino acidEssential amino acid
An essential amino acid or indispensable amino acid is an amino acid that cannot be synthesized de novo by the organism , and therefore must be supplied in the diet.-Essentiality vs. conditional essentiality in humans:...
in the human body and one of the few amino acids that directly cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. In the body, it is found circulating in the blood as well as stored in the skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
s. It becomes conditionally essential (requiring intake from food or supplements) in states of illness or injury.
Dietary sources
Dietary sources of L-glutamine include beef, chicken, fish, eggs, milk, dairy products, wheat, cabbage, beets, beans, spinach, and parsleyParsley
Parsley is a species of Petroselinum in the family Apiaceae, native to the central Mediterranean region , naturalized elsewhere in Europe, and widely cultivated as an herb, a spice and a vegetable.- Description :Garden parsley is a bright green hairless biennial herbaceous plant in temperate...
. Small amounts of free L-glutamine are also found in vegetable juices and foods such as tofu.
Aiding gastrointestinal function
In recent studies, glutamine-enriched diets have been linked with intestinal effects including maintenance of gut barrierEnterocyte
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells found in the small intestines and colon. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase surface area for the digestion and transport of molecules from the intestinal...
function and cell differentiation.
This may relate to the fact that the intestinal extraction rate of glutamine is higher
than that for other amino acids, and is therefore thought to be the most viable option when attempting to alleviate conditions relating to the gastrointestinal tract.
These conditions were discovered within the gut between glutamine-enriched and non-glutamine-enriched diets. However, even though glutamine is thought to have "cleansing" properties and effects, it is unknown to what extent glutamine has clinical benefits, due to the varied concentrations of glutamine in varieties of food.
Glutamine may help to protect the lining of the gastrointestinal tract or mucosa. It has been suggested that people who have inflammatory bowel disease IBD (ulcerative colitis and Crohn' s disease) may not have enough glutamine. However, two clinical trials found that taking glutamine supplements did not improve symptoms of Crohn' s disease. More research is needed.