GLUTAMINE INNUTRITIONAL MANANGMENT

Present by: Sajjad MoradiMs student of Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran

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INTRODUCTION Glutamine (abbreviated as Gln or Q, and

often called L-glutamine) one of the 20 amino acids encoded by

the standard genetic code Its codons are CAA and CAG

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INTRODUCTION Glutamine is the most abundant amino acid (building

block of protein) in the body It can be synthesized by the body and is therefore

not essential to the diet Glutamine serves as an important carrier of ammonia

and contributes it to the formation of urea and purines (which are essential to make DNA and RNA).

Most glutamine is stored in muscles followed by the lungs, where much of the glutamine is made

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INTRODUCTION In human blood, glutamine is the most

abundant free amino acid Its side-chain is an amide formed by replacing

the side-chain hydroxyl of glutamic acid with an amine functional group, making it the amide of glutamic acid

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Functions Protein synthesis, as any other of the 20 proteinogenic amino

acids Regulation of acid-base balance in the kidney by producing ammonium Cellular energy, as a source, next to glucose Nitrogen donation for many anabolic processes, including the synthesis of purines Carbon donation, as a source, refilling the citric acid cycle Nontoxic transporter of ammonia in the blood circulation

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Producers Glutamine is synthesized by the enzyme 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

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Glutamine and glutamate

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Consumers The most eager consumers of

glutamine are the cells of intestines the kidney cells for the acid-base

balance activated immune cells many cancer cells

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Dietary Sources Dietary sources of glutamine include plant and

animal proteins such as beef, pork and poultry, milk, yogurt, ricotta cheese, cottage cheese, raw spinach, raw parsley, and cabbage

Meat, poultry, fish and seafood are among the best sources of glutamine

Although they all contain ample amounts of protein, foods that supply higher levels of protein tend to be higher in glutamine

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Glutamine Metabolism

Glutamine is synthesized in the body from glutamate and glutamic acid by the action of glutamine synthetase

The primary site for glutamine synthesis is in skeletal muscle. The lungs, liver and brain are the secondary sites

Glutamine's key structural feature is that it contains two nitrogen atoms. This enables it to function as a nitrogen shuttle, carrying nitrogen between different organs and tissues

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Glutamine Metabolism

Glutamine is utilized primarily as a fuel source by tissues such as the small intestine, immune system and hair follicles

The GI tract alone accounts for 40% of the total glutamine utilized by the body

It is also utilized by a smaller extent in the kidneys and in the liver where it plays a vital role, assisting in numerous detoxification processes

Glutamine is able to cross the blood-brain barrier, where it is used as an energy source and a precursor for neurotransmitter substances

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Glutamine Metabolism

Glutamine transporters

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Glutamine and other amino acids

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Glutamine in nucleotide metabolism

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Glutamine in nucleotide metabolism

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Glutamine in brain

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Glutamine in brain

Glutamine in MUSCLE AND LIVER

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Glutamine in Kidney

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Medical uses In catabolic states of injury and illness, glutamine

becomes conditionally essential requiring intake from food or supplements

Supplementation does not appear to have an effect in infants with significant problems of the stomach or intestines

Glutamine has been used as a component of oral supplementation to reverse cachexia (muscle wasting) in patients with advanced cancer

HIV/AIDS

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Is Glutamine an Essential Fuel forCells? All cells have the capacity to transport and use

the full repertoire of amino acids Glutamate transporters were originally

believed to be highly concentrated only in the brain, liver, gut, and kidney

Glutamate transporters are expressed at moderate levels in most other tissues, including the heart, lung, and placenta.

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Is Glutamine an Essential Fuel forCells? Glutamine is a major substrate used by small intestinal

cells in the fed animal. Theoretically, there is a rationale for a unique role for

glutamine in cells, because it is metabolized to glutamate rapidly and extensively, and glutamate enters the Krebs cycle to be metabolized to alpha-ketoglutarate

In agreement with these metabolic pathways, the major energy sources for the small intestinal cell are glutamine, glutamate, and aspartate

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Glutamine in cellular protection Heat shock proteins (HsPs) protect cells by

preventing apoptosis and by acting as molecular chaperones to correct stress-related misfolding of proteins

A heat shock transcription factor (HsF-1) is activated in response to several stressors and increases the transcription of heat shock protein genes

The availability of glutamine in cell cultures is necessary for the expression of HsPs

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Glutamine in cellular protection glutamine supplementation enhances the

expression of HsPs in in vitro and in vivo studies In surgical intensive care patients, glutamine-

enriched parenteral nutrition increased HsP levels after 7 days, a finding that correlated with a decrease in ICU length of stay

Glutamine modulates intracellular signalling pathways involved in apoptotic changes. This may become a target of treatment in human sepsis

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Glutamine in cellular protection

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Glutamine in cellular protection

Gut barrier dysfunction Intestinal integrity is secured by intact cellular linings and

their tight junctions. It is jeopardized by glutamine depletion, oxidative stress, increased nitric oxide (NO) production, pro-inflammatory cytokines and prolonged parenteral nutrition

Gut barrier dysfunction may promote bacterial and endotoxin translocation

the release and preservation of glutathione (GsH), attenuation of inducible NO synthase (iNOs) expression maintaining tight junction functionality, rapid reduction of protein kinase C mediated hyperper meability in intestinal cells, attenuation of cytokine release, increased HsP expression and reduced gut mucosal apoptosis

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Anti-inflammatory action glutamine is able to induce an anti-inflammatory

response that may prove beneficial to the critically ill One of the first indications that glutamine could be a

modulator of inflammatory cytokine production For patients in this trial, glutamine-enriched enteral

nutrition reduced levels of soluble TNF receptors NFκB signalling pathways→ reduced levels of pro-

inflammatory cytokines (TNF-α, IL-6, IL-18) and improved survival

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Immune modulation The expression of major histocompatibility

complex class II antigens (HLA-DR) on monocytes is a prerequisite for effective antigen presentation to CD4+ T cells, which is an important component of immune response to infection

Surgery, trauma and inflammation reduce HLA-DR expression on monocytes

postoperative administration of glycyl-glutamine was accompanied by a smaller reduction in HLA-DR expression

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Immune modulation

The preservation of HLA-DR expression on monocytes was also found in trauma patients receiving glutamine-enriched enteral nutrition Both parenteral and enteral glutamine administration seem to preserve HLA-DR expression on monocyte

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Immune modulation

Glutamine and oxidative stress In the critically ill, oxidative stress contributes

to tissue injury and influences clinical outcome The redox potential influences the cellular

capability to scavenge free radicals derived from oxygen and also influences several intracellular mechanisms.

A regulator of cellular redox potential is GsH, a potent anti-oxidant During critical illness, plasma GsH levels decrease

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Glutamine and oxidative stress Glutamine is essential for GsH synthesis and

may therefore help to reduce oxidative stress In trauma patients, parenteral glutamine

supplementation has been found to attenuate GsH depletion in skeletal muscle

Early enteral nutrition with high dose glutamine (50-60g) and antioxidants improved the sequential organ failure assessment score

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Glutamine and oxidative stress Glutamine may also attenuate oxidative stress by

increasing plasma taurine levels Taurine, an amino acid with anti-oxidative

properties, is present in large amounts within the cell itself

trauma and sepsis plasma taurine levels decrease in response to surgical injury

by using enteral glutamine supplements, an increase in plasma taurine levels could be achieved in trauma patients and stressed rats

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Preservation of insulin sensitivity Glutamine has been found to preserve insulin

sensitivity in animal studies and critically ill patients severe illness is accompanied by reduced insulin

sensitivity, which leads to hyperglycaemia tight glucose control through the administration of

insulin, reduced morbidity and mortality in ICU patients

Glutamine blunted the effect of insulin on glucose production and enhanced insulin-mediated glucose utilization

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Preservation of insulin sensitivity In rats on a high fat diet, glutamine prevented weight gain

by inducing insulin resistance in adipose tissue, thus preventing lipogenesis, while it improved liver and peripheral insulin sensitivity

Decreased TNF-α production and NFκB activation were observed, suggesting that glutamine influences glucose and fat metabolism by reducing pro-inflammatory pathways

In a multicenter randomized controlled trial in 114 surgical and trauma ICU patients, glutamine supplementation resulted in reduced hyperglycaemic events

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SPORT uses Oral glutamine supplements are purported to: boost athletic performance promote muscle gain, and/or repair improve immune function after physical stress During exercise, glutamine concentrations in

the body may change depending on the type, duration, and intensity of exercise

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Why is Glutamine Important in Sports Nutrition? Because athletes subject their bodies to high levels of

physical (and mental) stress, many nutrients, including glutamine, are required at levels above those of a non-training person

If a sufficient quantity and quality of a nutrient is not obtained in the diet, or is unable to be manufactured by the body at the required rate, depletion occurs

This can contribute to sub-optimal performance and slow recovery

Supplementation to insure dietary intake is adequate becomes an important consideration

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Safety of Orally Administered L-Glutamine Glutamine is absorbed efficiently by the human

gastrointestinal tract Acute oral ingestion of glutamine at doses up

to 0.3 grams per kg of body weight showed no evidence of clinical toxicity (i.e. approximately 21 grams for 70kg person)

Oral supplementation is an effective and safe means of providing additional free glutamine to the body

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Glutamine: When and How Much

It is known that muscle glutamine levels decline in a dose-dependent manner to the degree of stress (i.e. greater the stress, the greater the loss), thus the need for glutamine is variable for different athletes

The daily requirement of glutamine for an athlete is between 8 to 20 grams, depending upon the dietary intake of glutamine containing foods, health and frequency and intensity of exercise

Glutamine supplementation ranging from 2 to 6 grams, two to four times throughout the day is suggested

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Glutamine: When and How Much There is no preferred time for

glutamine administration. It is suggested one dose early in the morning and one either prior to or after a workout or training session will assist in maintaining plasma levels of glutamine and may confer anti-catabolic protection

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Possible Interactions If you are currently being treated with any of the following

medications, you should not use glutamine supplements without first talking to your health care provider

Cancer therapy glutamine may increase the effectiveness and reduce the side effects of chemotherapy treatments with doxorubicin, methotrexate, and 5-fluorouracil in people with colon cancer.

Preliminary clinical studies suggest that glutamine supplements may prevent nerve damage associated with a medication called paclitaxel, used for breast and other types of cancers

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Possible Interactions Medications used to prevent seizures affect

chemicals in the brain. Glutamine may also affect chemicals in the brain. By affecting chemicals in the brain, glutamine may decrease the effectiveness of medications used to prevent seizures

Some medications used to prevent seizures include phenobarbital, primidone (Mysoline), valproic acid (Depakene), gabapentin (Neurontin), carbamazepine (Tegretol), phenytoin (Dilantin), and others.

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