Can the body use D-amino acids? Unlocking their hidden metabolic roles

October 7, 2025 •

4 min read

For years, the scientific community focused almost exclusively on L-amino acids as the building blocks of life, considering their D-counterparts nutritionally irrelevant. However, recent advances in analytical techniques have revealed a surprising prevalence of diverse D-amino acids within mammalian tissues. This discovery leads to a critical question: can the body use D-amino acids, and if so, what are their functions?

Quick Summary

This article explores the biological roles of D-amino acids in humans, revealing their functions as signaling molecules in the nervous and endocrine systems. It details the enzymatic processes that metabolize and regulate these compounds, moving beyond the historical view that they are simply inactive or non-functional stereoisomers.

Key Points

Stereoisomers of L-amino acids: D-amino acids are mirror-image forms of the L-amino acids used to build proteins.
No protein synthesis role: The human body does not incorporate D-amino acids into its proteins.
Key signaling functions: Specific D-amino acids, like D-serine and D-aspartate, act as neurotransmitters and hormones in the nervous and endocrine systems.
Managed by specific enzymes: The body possesses specialized enzymes, such as D-amino acid oxidase (DAO), to metabolize and regulate D-amino acid levels.
Accumulation can be toxic: Without proper enzymatic breakdown, D-amino acid accumulation can be harmful, as seen in some disease contexts.
Multiple sources: D-amino acids can come from endogenous synthesis, food processing, and the metabolic activities of gut bacteria.

The study of amino acids has long been dominated by the L-form, as it is the configuration universally incorporated into proteins across mammalian species. This biological homochirality led to the widespread assumption that D-amino acids were either absent in higher organisms or simply metabolized and excreted as metabolic waste. However, modern biochemistry paints a much more complex and intriguing picture. It is now clear that while D-amino acids are not used for protein synthesis, they play distinct, active roles as signaling molecules and metabolic intermediates. These functions are crucial for understanding various physiological processes, from neurotransmission to gut immunity.

Understanding Chirality: The L vs. D Enantiomers

Amino acids, with the exception of glycine, exist as two non-superimposable mirror-image forms called enantiomers, designated L (levo) and D (dextro). This handedness, or chirality, is a fundamental property of their structure. In a Fischer projection, the amino group (-NH2) is on the left for L-amino acids and on the right for D-amino acids.

The biological significance of L-amino acids

All proteins in the human body are constructed from L-amino acids. The intricate three-dimensional structure of enzymes and protein receptors is designed to interact specifically with these left-handed forms. This specificity is why dietary proteins primarily consist of L-amino acids and why the body's protein-building machinery, involving messenger RNA (mRNA) and transfer RNA (tRNA), only recognizes L-isomers.

The Surprising Roles of D-Amino Acids in Mammals

Contrary to previous assumptions, D-amino acids are not just passive substances. Instead, they serve as potent signaling molecules with specific functions:

D-Serine: Abundant in the brain, D-serine acts as a co-agonist at N-methyl-D-aspartate (NMDA) receptors. These receptors are critical for synaptic plasticity, which underpins learning and memory. Dysregulation of D-serine and NMDA receptor function has been implicated in neurological conditions like schizophrenia and neurodegeneration.
D-Aspartate: Found in neuroendocrine tissues, D-aspartate is involved in regulating hormone synthesis and secretion from various endocrine glands, including the pituitary and testes.
D-Alanine and D-Cysteine: These and other D-amino acids have been linked to regulating innate immunity and modulating gut barrier function.

Metabolism and Regulation by Specific Enzymes

To manage the levels of these compounds, the body employs specialized enzymes that can interact with the D-stereoisomer, a key difference from the general protein-building machinery.

D-Amino Acid Oxidase (DAO): This flavoenzyme is found in the brain, liver, and kidneys. It catalyzes the oxidative deamination of neutral and basic D-amino acids, converting them into a-keto acids, ammonia, and hydrogen peroxide. For instance, DAO is a primary regulator of D-serine concentration in the brain.
D-Aspartate Oxidase: A separate enzyme specifically designed to metabolize D-aspartate.
Detoxification Pathway: The metabolic process mediated by enzymes like DAO serves to prevent the accumulation of D-amino acids, which could be toxic. This mechanism is crucial for maintaining metabolic homeostasis.

Sources of D-Amino Acids

Where do these D-amino acids come from?

Endogenous Synthesis: The body can produce some D-amino acids, such as D-serine, from their L-form counterparts via enzymes like serine racemase.
Dietary Intake: D-amino acids can be ingested through food. They naturally occur in some foodstuffs and can be generated during food processing, including high-temperature treatments, fermentation, and alkaline treatments. For example, dairy products can contain D-amino acids due to microbial activity or heat treatment.
Gut Microbiota: The bacteria residing in the gut produce and secrete various D-amino acids. These microbial D-amino acids can be absorbed and have been shown to influence mammalian physiology, including the immune system.

Comparison of L- and D-Amino Acids


Feature	L-Amino Acids	D-Amino Acids
Chirality	Amino group on the left in Fischer projection	Amino group on the right in Fischer projection
Role in Proteins	The standard form used for building all human proteins	Generally not incorporated into mammalian proteins
Primary Function	Structural components for proteins and enzymes	Signaling molecules (neurotransmitters, hormones) and metabolic intermediates
Metabolism	Metabolized by a wide array of enzymes for protein synthesis and energy	Metabolized by specific enzymes like D-amino acid oxidase (DAO)
Absorption	Primarily absorbed via active, carrier-mediated transport	Absorbed through passive diffusion and, less efficiently, via transporters
Nutritional Value	High, as they are the building blocks for bodily proteins	Low for protein synthesis, but possess distinct biological activities

Conclusion

While the human body does not incorporate D-amino acids into proteins, it has evolved a sophisticated system to absorb, metabolize, and utilize these mirror-image molecules for specialized, non-protein functions. From fine-tuning neurotransmission in the brain to regulating gut immunity, the biological significance of D-amino acids is now widely acknowledged. This shift in understanding from metabolic waste to crucial signaling molecules highlights the intricate complexity of human nutrition and biochemistry. The discovery and functional characterization of these lesser-known amino acid forms continue to provide new insights into health and disease, challenging former theories about mammalian physiology.

For more information, see: D-Amino Acids in the Nervous and Endocrine Systems

Frequently Asked Questions

Yes, D-amino acids can be absorbed by the body, although their absorption mechanism differs from L-amino acids. They are absorbed primarily through passive diffusion and, to a lesser extent, via transporters in the intestine.

No, D-amino acids are not incorporated into proteins in the human body. The cellular machinery responsible for protein synthesis is stereospecific and exclusively uses the L-form of amino acids.

D-serine functions as a neurotransmitter in the brain, where it acts as a co-agonist for NMDA receptors. These receptors are vital for brain functions like synaptic plasticity, learning, and memory.

If not properly metabolized, the accumulation of certain D-amino acids can have detrimental effects. For example, some D-amino acids have been linked to neuro-toxic effects and may be associated with conditions like Alzheimer's disease.

D-amino acids are metabolized by specific enzymes, most notably D-amino acid oxidase (DAO) and D-aspartate oxidase. These enzymes break down the D-forms into α-keto acids, ammonia, and hydrogen peroxide.

D-amino acids have several sources, including endogenous synthesis within the body, formation during food processing (e.g., heating, fermentation), and production by gut bacteria.

The primary difference is their spatial arrangement, or chirality, making them mirror images of each other. L-amino acids are used for building proteins, while D-amino acids serve as specialized signaling and regulatory molecules in mammals.

Yes, D-amino acids can be found in food. They may be present naturally in certain items or can be generated during food processing, including heat and fermentation.