Alanylglutamine: A Comprehensive Overview

1) Conditions Studied

Alanylglutamine, also known as alanyl-l-glutamine or dipeptide L-alanyl-L-glutamine, has been studied for a variety of conditions, including:

• Improving intestinal health in individuals with gastrointestinal disorders.
• Enhancing recovery and immune function in critically ill patients.
• Reducing muscle wasting and supporting metabolism in patients with cachexia or critical illnesses.
• Supporting hydration and electrolyte balance in athletes.

2) Efficacy in Treating Conditions

Studies have shown mixed results regarding the efficacy of alanylglutamine in treating the above conditions. While some research suggests it can help improve intestinal function and support hydration, its overall effectiveness can vary based on the specific condition and individual patient characteristics.

3) Health Benefits

Alanylglutamine has been associated with several potential health benefits, including:

• Supporting gut health and integrity.
• Enhancing immune response and reducing infection rates in hospitalized patients.
• Improving nutrient absorption and metabolism.
• Potentially aiding in muscle recovery and reducing exercise-induced muscle damage.
• Assisting in maintaining hydration and electrolyte balance.

4) Potential Downsides

While alanylglutamine is generally considered safe, there are potential downsides, including:

• Mild gastrointestinal issues in some individuals.
• Potential interactions with certain medications or health conditions.
• Overuse may lead to imbalances in amino acid levels.

It's always recommended to consult with a healthcare provider before starting any new supplement regimen.

5) Effects on Genetic Variations

Currently, there is limited research on the relationship between alanylglutamine and specific genetic variations. However, individual differences in metabolism and nutrient absorption could potentially influence how one responds to alanylglutamine supplementation. More research is needed to understand the genetic factors that may affect its benefits or risks.

Summary on Alanylglutamine

Alanylglutamine (Ala-Gln) is a dipeptide synthesized using an enzymatic method in Escherichia coli overexpressing α-amino acid ester acyltransferase from Sphingobacterium siyangensis. Optimized conditions allowed for a yield of 69.7 g/L Ala-Gln with a 67% molar yield. Genetic modifications in E. coli increased precursor amino acid availability and reduced dipeptide degradation, enabling over 100 mM Ala-Gln production extracellularly during fed-batch cultivation. This method avoids non-natural amino acids and longer peptides, showing promise for clinical and nutritional applications of Ala-Gln.

Ala-Gln supplementation is essential for critically ill patients, as glutamine can become insufficient during severe illness, affecting immune cells and nucleotide synthesis. It is standard care for patients on parenteral nutrition, with 20-25 grams per day normalizing plasma levels without adverse effects. Oral rehydration based on Ala-Gln was found to be more effective than glutamine-based solutions in treating secretory diarrhea in a rat model, suggesting potential for human clinical trials.

Ingesting Ala-Gln raises plasma L-glutamine levels more effectively than free L-glutamine or hydrolyzed wheat protein, maintaining elevated levels for a longer duration. This dipeptide also improves endurance exercise performance by enhancing fluid and electrolyte uptake during mild hydration stress. Alanylglutamine has been shown to protect against oxidative injury in the gut, maintaining cellular antioxidants and PepT1 protein levels, which are important for small peptide absorption.

Synthetic glutamine dipeptides like Ala-Gln are stable, soluble, and can be industrially produced, making them suitable for clinical use. They improve nitrogen balance, immune function, and gut integrity, reducing hospital stays and mortality. The oligopeptide transporter Pept-1, crucial for absorbing proteins in the intestine, specifically transports dipeptides but not larger peptides or individual amino acids. Alanylglutamine supplementation in total parenteral nutrition preserves intestinal structure and function in rats, and protects against mucosal damage from ischemia-reperfusion injury.

Studies on rats show that oral supplementation with either the dipeptide (Ala-Gln) or a combination of free L-glutamine and L-alanine reduces muscle damage and oxidative stress from high-intensity exercise. In addition, Ala-Gln supplementation maintains higher muscle and plasma glutamine levels after exhaustive exercise. Carbohydrate supplementation can prevent increased branched-chain amino acid oxidation during exercise, while amino acids like glutamine are critical for the energy metabolism of exercising muscles. Intravenous infusion of alanylglutamine is predominantly cleared by the kidneys, significantly affecting plasma levels of free alanine and glutamine.

References:

1. Enzymatic production of L-alanyl-L-glutamine by recombinant E. coli expressing α-amino acid ester acyltransferase from Sphingobacterium siyangensis
2. Fermentative production of L-alanyl-L-glutamine by a metabolically engineered Escherichia coli strain expressing L-amino acid alpha-ligase
3. Clinical use of glutamine supplementation
4. L-glutamine absorption is enhanced after ingestion of L-alanylglutamine compared with the free amino acid or wheat protein
5. Effects of an alanyl-glutamine-based oral rehydration and nutrition therapy solution on electrolyte and water absorption in a rat model of secretory diarrhea induced by cholera toxin
6. Examination of the efficacy of acute L-alanyl-L-glutamine ingestion during hydration stress in endurance exercise
7. New developments in glutamine delivery
8. The oligopeptide transporter (Pept-1) in human intestine: biology and function
9. Alanylglutamine dipeptide and growth hormone maintain PepT1-mediated transport in oxidatively stressed Caco-2 cells
10. Expression of the peptide transporter hPepT1 in human colon: a potential route for colonic protein nitrogen and drug absorption
11. Alanyl-glutamine dipeptide-supplemented parenteral nutrition improves intestinal metabolism and prevents increased permeability in rats
12. Alanyl-glutamine-supplemented parenteral nutrition prevents intestinal ischemia-reperfusion injury in rats
13. Alanyl-glutamine and glutamine plus alanine supplements improve skeletal redox status in trained rats: involvement of heat shock protein pathways
14. Effects of supplementation with free glutamine and the dipeptide alanyl-glutamine on parameters of muscle damage and inflammation in rats submitted to prolonged exercise
15. Effects of oral supplementation with glutamine and alanyl-glutamine on glutamine, glutamate, and glutathione status in trained rats and subjected to long-duration exercise
16. Effect of alanyl-glutamine supplementation on plasma and tissue glutamine concentrations in rats submitted to exhaustive exercise
17. Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism
18. Carbohydrate supplementation, glycogen depletion, and amino acid metabolism during exercise
19. Splanchnic, renal, and muscle clearance of alanylglutamine in man and organ fluxes of alanine and glutamine when infused in free and peptide forms
20. Cloning and structural analysis of genomic DNA for human renal dipeptidase
21. Gene structural analysis and expression of human renal dipeptidase
22. L-Alanylglutamine inhibits signaling proteins that activate protein degradation, but does not affect proteins that activate protein synthesis after an acute resistance exercise
23. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice
24. AMPK activation stimulates myofibrillar protein degradation and expression of atrophy-related ubiquitin ligases by increasing FOXO transcription factors in C2C12 myotubes
25. The effect of amino acid analogues and heat shock on gene expression in chicken embryo fibroblasts
26. Transient rates of synthesis of individual polypeptides in E. coli following temperature shifts
27. Heat shock proteins and thermal resistance in yeast
28. The heat shock response: life on the verge of death
29. Human skeletal muscle HSP70 response to physical training depends on exercise intensity
30. L-alanyl-L-glutamine ingestion maintains performance during a competitive basketball game
31. Two percent dehydration impairs and six percent carbohydrate drink improves boys basketball skills
32. The effect of water restriction on anaerobic power and vertical jumping height in basketball players
33. Progressive dehydration causes a progressive decline in basketball skill performance
34. Improvement of intestinal permeability with alanyl-glutamine in HIV patients: a randomized, double blinded, placebo-controlled clinical trial

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