Threonine, an essential amino acid, must be obtained through diet as the human body cannot synthesize it. 

Beyond its basic nutritional role, threonine is crucial for various physiological functions, including cellular homeostasis, energy metabolism, macromolecular biosynthesis, and gut health. 

It is vital for producing gastrointestinal mucin and modulating the intestinal immune system via signaling pathways like MAPK and TOR. 

Threonine is indispensable for cell growth and proliferation, influencing lipid metabolism and protein synthesis, particularly in skeletal muscles. 

Furthermore, it plays a significant role in embryonic stem cell function and epigenetic regulation. 

The metabolism of threonine, which can produce glycine, acetyl CoA, and pyruvate, involves key enzymes such as threonine dehydrogenase (TDH) and threonine dehydratase (STDH), with different pathways active depending on physiological states. 

In humans, threonine primarily follows the dehydratase pathway, but during fasting or high protein intake, alternative pathways may become significant. 

This comprehensive role underscores threonine's importance in nutrition and health management.

What is Threonine? 

Threonine is an essential amino acid, meaning it cannot be synthesized by the human body and must be obtained from dietary sources.

Above and beyond its role as an essential amino acid, Threonine is an important regulator of cellular homeostasis.

It is important in nutritional metabolism, macromolecular biosynthesis, gut homeostasis, and the modulation of energy metabolism. 

Threonine is a vital component of gastrointestinal mucin and influences the intestinal immune system via signaling pathways such as MAPK and TOR. 

It's indispensable for cell growth and proliferation, and optimizing Threonine intake can positively impact animal health and disease resistance.

Threonine is also a precursor to glycine. [9.]

Functions of Threonine [15.]

Metabolic Pathways of Threonine 

Threonine serves as a substrate for protein synthesis, particularly mucin.

It can be metabolized via Three different pathways to produce glycine, acetyl CoA, and pyruvate, essential for various metabolic processes.

Threonine dehydrogenase (TDH) and Threonine dehydratase (STDH) are key enzymes in Threonine metabolism, with different pathways depending on physiological states.

Lipid Metabolism 

Threonine enhances hepatic lipid metabolism and protects against hepatic triglyceride accumulation by regulating lipogenesis signaling pathways and thermogenic gene expression.

Protein Synthesis

Threonine is crucial for synthesizing Threonine-rich proteins like mucins, enhancing protein synthesis in tissues such as skeletal muscle. It activates signaling pathways (e.g., PI3K/AKT/TOR) that promote muscle protein synthesis and suppress proteolysis.

Effects on Embryonic Stem Cells (ESCs)

Threonine supports ESC proliferation and differentiation by providing substrates for macromolecular biosynthesis and energy production.

It plays a role in epigenetic regulation, necessary for chromatin modifications and maintaining pluripotency in ESCs.

Intestinal Health and Functions

Uptake and Utilization

A significant portion of dietary Threonine is utilized by the gut for protein synthesis and mucosal health.

Nutrient Digestibility

Threonine supplementation improves intestinal structure, nutrient absorption, and enzyme activity.

‍Gut Microbiota

Threonine positively impacts gut microbiota, promoting beneficial bacterial populations and mucin secretion.

Barrier Function

Threonine is essential for mucin-2 production, maintaining the mucus layer that protects the gut lining. It regulates goblet cell differentiation and mucin synthesis, crucial for intestinal health, especially under stress conditions.

Immune Function

Threonine supports gut immune function by influencing lymphocyte proliferation, immunoglobulin production, and cytokine expression. It modulates inflammatory responses via pathways like NF-κB and TOR, enhancing overall immune defense.

Threonine's comprehensive role in lipid metabolism, protein synthesis, ESC function, and intestinal health underscores its importance in animal nutrition and health management. Further research is needed to explore its regulatory mechanisms in different animal models and its interaction with intestinal microbiota, immune response, and barrier functions.

Threonine Biochemical Pathways

Major Threonine Metabolism Pathways

There are three main metabolic pathways for threonine processing.

Threonine Dehydrogenase Pathway [3.]

This enzyme is active in bacteria and in some animals, but not in humans.

The human L-threonine 3-dehydrogenase (TDH) gene is classified as an expressed pseudogene. Located at 8p23-22, the gene has 8 exons spanning 10 kb, but due to three mutations, it encodes non-functional truncated proteins. 

Consequently, the resulting TDH proteins lack critical parts of the NAD+ binding motif and the C-terminal domain necessary for L-threonine binding. 

TDH mRNA is present in various tissues, indicating that the gene is still transcribed despite its non-functional status. 

However, some research shows that his pathway does have some minor functionality in humans. This pathway converts threonine into 2-amino-3-ketobutyrate, subsequently cleaved into glycine and acetyl-CoA. [2.] 

Interestingly, in human infants, the threonine dehydrogenase pathway is more significant, accounting for 44% of threonine oxidation, suggesting age-related differences in threonine metabolism. [2.] 

Threonine Dehydratase (Serine Dehydratase) Pathway [2.]

In humans, this is the primary pathway for threonine catabolism. Threonine is converted to α-ketobutyrate by threonine dehydratase (also known as serine dehydratase). This reaction is analogous to the serine dehydratase reaction and is likely catalyzed by the same enzyme in the liver.

This pathway converts threonine into 2-ketobutyrate and ammonia, with 2-ketobutyrate rapidly oxidized to CO2. 

Threonine Kinase Pathway

Various isoforms of threonine kinase exist, with different functions. 

Generally, threonine kinases phosphorylate the hydroxyl group of threonine residues on proteins, converting them into phosphothreonine as part of various signaling and regulatory processes within the cell. [4.]

For example, the CK1 family of threonine kinase enzymes are involved in various biological processes including cell cycle regulation, circadian rhythm maintenance, Wnt signaling, Hippo signaling, Hedgehog signaling, and apoptosis. [4.]

These phosphorylated threonine residues also play critical roles in T cell signaling, metabolism, and immune responses. [8.]

Factors Affecting Threonine Metabolism [15.] 

The pathways of threonine metabolism are affected by different physiological states, including the following:

Fasting and Starvation

During fasting and starvation, threonine is primarily metabolized via the glycine-independent pathway. 

In this state, threonine is catalyzed to α-ketobutyric acid and ammonia by liver threonine dehydratase (STDH), which is then decarboxylated to form propionyl-CoA.

Normal Adult Metabolism

In adults, threonine metabolism includes both the glycine-independent pathway (via STDH) and the glycine-dependent pathway (via threonine dehydrogenase (TDH) and threonine aldolase). 

About 7-10% of total threonine is catabolized by the TDH pathway in adults, meeting the body's glycine requirements.

Infant Metabolism

In infants, threonine is exclusively degraded by the STDH pathway (glycine-independent). This is because infants have higher glycine requirements compared to adults.

These physiological states influence the choice of metabolic pathway for threonine, impacting how it is utilized and metabolized in the body.

Health Benefits of Threonine

Supports Digestive Health [15.] 

Threonine helps produce a protective mucus gel layer that covers the digestive tract, acting as a barrier against damaging digestive enzymes.

It promotes the protective effects of the gut mucus barrier and supports healthy gut function.

Boosts Immune System [8.] 

The thymus gland uses threonine to make T-cells that help fight infections.

Threonine is involved in controlling immune system functions through its role in serine/threonine kinases. 

Supports Liver Health [12.] 

Threonine acts as a lipotropic agent, helping control fat buildup in the liver.  It does this by maintaining liver mitochondrial function and overall liver health. Threonine deficiency has been shown in animal models to alter energy processing in the liver, including fat metabolism. 

Supports Muscle and Bone Strength 

Threonine is important for the formation of collagen and elastin, which are crucial for muscle and connective tissue strength. [17.] 

It helps maintain proper protein balance in the body.

Wound Healing

Higher serum levels of threonine are associated with better healing outcomes in diabetic foot ulcer patients. [5.] 

May Improve Muscle Contractions

Threonine is an essential amino acid that acts as a precursor to glycine, which may help manage spasticity by increasing glycine levels in the central nervous system.

However, results are mixed. [9.]

May Improve Sleep

Some research suggests threonine may have sleep-promoting effects that could help with insomnia and sleep disorders. 

The link between amino acid processing, including threonine, and sleep have been demonstrated in fruit flies, providing a mechanistic pathway and indicating that more research may provide additional insights into human sleep patterns. [6.]

Foods High in Threonine

Food Sources of Threonine

Threonine can be obtained from dietary sources, primarily from protein-rich foods such as meat, poultry, fish, eggs, and dairy products. Plant-based sources of Threonine include legumes, nuts, and seeds.

For individuals with specific dietary restrictions or increased Threonine requirements, Threonine supplements are available in various forms, including capsules, tablets, and powders.

Threonine Safety Considerations and Recommended Dosages

While Threonine is generally considered safe when consumed in recommended amounts, excessive intake may lead to adverse effects. 

It is essential to follow dosage guidelines and consult with healthcare professionals, especially for individuals with underlying medical conditions or taking medications.

Dosages may range from a few hundred milligrams to several grams per day, depending on the intended use and individual requirements. Always consult with a medical professional prior to initiating new supplements. 

Testing Threonine Levels

Test Information, Sample Collection and Preparation

Amino acids including Threonine may be tested in blood or urine. Blood tests require a venipuncture, while urine samples may be collected from the comfort of home. 

Fasting is generally required prior to sample collection. It is important to consult with the ordering provider prior to sample collection to determine whether certain supplements should be avoided. 

Plasma vs. Urine Assessment of Amino Acids

Plasma amino acid testing and urine amino acid testing are both valuable diagnostic tools used to assess amino acid metabolism and provide insights into various aspects of health. However, each method offers distinct advantages. 

Plasma amino acid testing involves the analysis of amino acid levels in the bloodstream, offering real-time information about amino acid concentrations and their role in metabolic processes. 

This method provides a snapshot of amino acid status and allows clinicians to identify immediate metabolic dysregulation, amino acid deficiencies, and imbalances in metabolic pathways. 

Additionally, plasma amino acid testing enables the evaluation of amino acid levels associated with neurotransmitter synthesis, providing insights into neurotransmitter balance and cognitive health. [10.]  A plasma sample is also recommended when kidney function is compromised.

Recent food intake briefly elevates plasma levels, making fasting samples preferable. While short-term fasting doesn't deplete plasma amino acids, long-term malnutrition does. 

Despite good correlation between plasma and urine amino acids, urine samples represent recent dietary intake and metabolism, offering insight into fluctuating diets or controlled dietary changes. 

Urine samples, collected conveniently at home, are suitable for assessing controlled diets or recent dietary modifications, although results are influenced by kidney function, with biomarkers ratioed to urine creatinine.

In contrast, urine amino acid testing offers a comprehensive view of amino acid excretion and metabolic waste products.  [11.]   

While urine amino acid testing may not provide real-time information about amino acid concentrations in the bloodstream, it offers valuable insights into amino acid metabolism and renal function.

Urine amino acid testing is often used to screen for inborn errors of amino acid metabolism, although it is also used in assessing long-term metabolic health and monitoring treatment responses over time. [1.]

Interpreting Threonine Test Results

Optimal Levels of Threonine

Threonine levels should be interpreted within the context of an individual’s full medical history, depending on the sample type used. 

One laboratory company recommends a plasma Threonine level between 6-17 μmoles/100ml.

[13.] 

Another laboratory company recommends a random or first-morning urine Threonine level between 60-230 micromol/g creatinine. [14.] 

Clinical Significance of Excessive Threonine Levels

Although rare, excessively high Threonine levels may indicate excessive supplementation or decreased metabolism and utilization of Threonine. 

Animal studies have shown increased threonine levels in the setting of low-protein diets and/or metabolic shifts. [7.]

Clinical Significance of Decreased Threonine Levels

Decreased Threonine levels may be associated with malnutrition or poor protein intake, or digestive insufficiency. In urine tests, low levels of amino acids such as Threonine may signal kidney disease. 

FAQ: Threonine

Threonine is an essential amino acid that is crucial for various bodily functions. It plays a significant role in protein synthesis and maintaining proper muscle and connective tissue health. This FAQ section addresses common questions about Threonine, its benefits, sources, and potential deficiency symptoms.

What is Threonine?

Threonine is an essential amino acid that the body cannot produce on its own and must be obtained through diet. It is a building block for proteins and is involved in various metabolic processes.

What are Threonine’s Benefits?

Threonine offers several benefits including supporting the formation of collagen and elastin, which are important for healthy skin and connective tissues. It also aids in liver function, immune system support, and fat metabolism.

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What is a Threonine Supplement?

A Threonine supplement is a dietary supplement that provides an additional source of Threonine. It is often used by individuals who may not get enough Threonine from their diet, such as athletes, vegetarians, or those with specific health conditions.

What are Threonine Deficiency Symptoms?

Symptoms of Threonine deficiency can include digestive issues, fatty liver, muscle weakness, and impaired immune function. Since Threonine is essential for protein synthesis, a deficiency can also lead to poor overall growth and development.

What Foods have Threonine?

Threonine is found in high-protein foods. Good sources include meat, fish, dairy products, eggs, nuts, seeds, beans, and lentils. Incorporating these foods into your diet can help ensure you get an adequate amount of Threonine.

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