Protein and the Brain

All life requires proteins — tiny biological machines that perform specific functions. Therefore, in humans, all bodily functions require action from these essential biomolecules. This is especially true for maintaining the most complex human organ — the brain. To keep the brain running, all the necessary proteins need to be produced by brain cells, at the right time and in the appropriate proportion. Therefore, lacking important brain proteins could lead to cognitive deficiencies such as dementia (e.g. Alzheimer’s disease) that can severely impact quality of life.

Knowing this, how can we maintain proper protein activity in the brain? One way we can achieve this is by providing the brain with amino acids, which are the building blocks of protein. Just twenty amino acids generally form the basis for most proteins. However, this is not their only role. Amino acids are also used as scaffolds to produce unique amino acid by-products which can be used as signaling molecules for cell-to-cell communication.

What are Amino Acids?

Amino acids serve as the fundamental components of proteins, which are essential macromolecules in biological systems. Proteins are composed of long chains of amino acids linked together in specific sequences. These sequences determine the structure and function of each protein, enabling a vast array of biological activities critical for maintaining life. The human body contains thousands of distinct proteins, each tailored for unique physiological roles.

To conceptualize this, amino acids can be like letters in an alphabet. By arranging letters in diverse combinations, we construct different words. Similarly, arranging amino acids in varying sequences forms proteins with distinct structures and functions, highlighting their importance in biological processes.

What do Amino acids do?

Amino acids are indispensable to numerous physiological processes, primarily serving as the foundational units for protein synthesis. The specific types and arrangements of amino acids within a protein dictate its structure and function, enabling the body to perform a wide range of critical activities. Key functions of amino acids include:

• Facilitating Nutrient Metabolism: Amino acids are essential for the breakdown of food, aiding in converting dietary macronutrients into usable energy and molecules.
• Tissue Growth and Repair: They play a central role in the growth, repair, and maintenance of body tissues, including muscles, skin, and organs.
• Synthesis of Hormones and Neurotransmitters: Many amino acids are precursors for hormones and neurotransmitters, which regulate metabolic processes and facilitate communication within the nervous system.
• Energy Provision: Certain amino acids can be metabolized as an alternative energy source, especially during prolonged fasting or intense physical activity.
• Support for Skin, Hair, and Nail Health: Amino acids contribute to the production of structural proteins, such as keratin and collagen, which are vital for maintaining healthy skin, hair, and nails.
• Muscle Development: They are integral to muscle protein synthesis, making them crucial for building and maintaining muscle mass.
• Immune Function: Amino acids enhance immune system responses by supporting the production of antibodies and immune cells.
• Digestive Health: They contribute to the integrity and function of the digestive system, supporting processes like nutrient absorption and gut barrier maintenance.

Through these diverse roles, amino acids are fundamental to maintaining the body’s overall health and ensuring optimal physiological function.

What are the Different Types of Amino Acids?

The human body requires 20 distinct amino acids to perform essential physiological functions. These amino acids combine in various configurations to form proteins, which are vital for numerous biological processes. While the body synthesizes many amino acids, there are nine that it cannot produce. These are termed essential amino acids, as they must be obtained from dietary sources. The remaining amino acids, produced by the body, are classified as nonessential amino acids. A subset of nonessential amino acids, known as conditionally essential amino acids, become crucial during periods of illness or stress.

Essential Amino Acids

1. Histidine: A precursor to histamine, a neurotransmitter essential for immune responses, digestion, sleep regulation, and sexual function.
2. Isoleucine: Plays a role in muscle metabolism, immune support, hemoglobin production, and energy regulation.
3. Leucine: Facilitates protein synthesis, muscle tissue growth and repair, wound healing, and blood sugar regulation.
4. Lysine: Critical for hormone production, energy generation, calcium absorption, and immune system function.
5. Methionine: Supports tissue growth, metabolic processes, detoxification, and the absorption of essential minerals like zinc and selenium.
6. Phenylalanine: A precursor for neurotransmitters, including dopamine, epinephrine, and norepinephrine. It also contributes to the synthesis of other amino acids.
7. Threonine: Integral to the production of collagen and elastin, structural proteins vital for skin and connective tissue health. It also aids in blood clot formation, fat metabolism, and immune function.
8. Tryptophan: Essential for maintaining nitrogen balance and synthesizing serotonin, a neurotransmitter involved in mood, appetite, and sleep regulation.
9. Valine: Supports muscle growth, tissue repair, and energy production.

Nonessential Amino Acids

The body can synthesize the following 11 amino acids under normal conditions:

• Alanine
• Arginine
• Asparagine
• Aspartic Acid
• Cysteine
• Glutamic Acid
• Glutamine
• Glycine
• Proline
• Serine
• Tyrosine

Certain amino acids, classified as conditionally essential, become vital under specific circumstances such as illness or physiological stress when the body’s ability to synthesize them is insufficient. These amino acids include arginine, cysteine, glutamine, tyrosine, glycine, ornithine, proline, and serine. During periods of heightened physical demand or compromised health, the body's requirements for these amino acids increase, necessitating additional intake through diet or supplementation to support recovery and maintain proper physiological function.

Given the diversity of amino acids, which ones are crucial for brain health? Some famous examples include:

• Tryptophan: Tryptophan is the precursor for the creation of the behavioral neurotransmitter serotonin. Thus, tryptophan levels are correlated with serotonin levels, thereby impacting feelings such as depression and alertness. One small study showed that patients who did not receive a dietary supplement of tryptophan were observed to be more vulnerable to depressive episodes than those who had received it. Interestingly, tryptophan produced in the body can contribute to either making proteins or it can be used to produce a by-product called kynurenine. It has been noted that changes in kynurenine concentration may be linked to the etiology of depression.
• Arginine: Arginine levels have been connected to a variety of neurological effects and disorders. Observations from brain samples of Alzheimer’s disease patients showed significant changes in the metabolism of both arginine and several arginine-related molecules. Arginine is also the precursor for another molecule called creatine. Deficiency in creatine production, which may stem from a lack of arginine, can result in speech impediments and epilepsy. Some researchers have also suggested that arginine concentrations in the body may be related to depression. Studies have shown that some major depressive disorder patients exhibit decreased arginine concentrations. Furthermore, depression patients taking prescribed medication had higher levels of arginine than the tested non-patient samples. While this is an interesting connection, further studies are ongoing to account for the variation across populations.

What Foods are High in Amino Acids?

If you are informed by a healthcare provider that amino acid supplementation may be beneficial or would like to attempt nutritional psychiatry with amino acid supplements, one actionable strategy is to make dietary changes. Conveniently, in the case of tryptophan and arginine, many similar foods can act as a source for boosting these amino acids. Dairy (e.g., milk and cheese), nuts (e.g., peanuts), and poultry meats (e.g., turkey and chicken) are all readily available sources of arginine and tryptophan. Although we have only highlighted two examples, there are still many more molecules amongst the twenty standard amino acids and their related by-products (e.g., proline, L-theanine, cysteine, gamma-aminobutyric acid) which are being investigated for their effects on the nervous system and mental health.

Despite the importance of amino acids to human health, the cells in our bodies are not able to produce all of them. Our inability to produce essential amino acids has led to their outsourced production by the resident microbiota of our intestinal tracts. Subsequently, this can lead to their uptake and use by the human host via the gut-brain axis. For example, it has been suggested that the production of the amino acid lysine and subsequent intake by the human host is up to 20% and can be traced back to the residential bacteria of the small and large intestines.

The interplay between amino acids and the nervous system in humans is an incredibly complex picture. Given their importance to the brain (and subsequently mental health) we should be exploring all avenues that help us understand how we can utilize amino acids to improve our daily lives with appropriate diets and supplementation.