Aspartic acid

Aspartic acid, represented by the symbols Asp or D, is an alpha amino acid central to numerous biochemical processes in living organisms. In its deprotonated form, it is known as aspartate, a term typically used under physiological conditions where the side chain carries a negative charge. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids incorporated into proteins, whereas the D-isomer has specialised but more limited biological roles, including participation in specific peptides and neuromodulatory signalling. Its chemical versatility and reactivity make aspartic acid a significant component in protein structure, metabolic pathways and industrial applications.

Structure and Chemical Properties

Like all amino acids, aspartic acid possesses an amino group and a carboxylic acid group bound to a central alpha carbon. Under physiological conditions, the amino group exists predominantly in its protonated ammonium form (NH₃⁺), while the carboxyl group is deprotonated (COO⁻). Its side chain, CH₂COOH, is also acidic, conferring a negative charge at approximately pH 7.4 and classifying aspartic acid, along with glutamic acid, as an acidic amino acid.
The side chain’s ability to form hydrogen bonds supports secondary-structure motifs such as asx turns and asx motifs, especially at the N-termini of alpha helices. The pKa of the side chain is around 3.9, but in peptide environments this may vary widely depending on local interactions, sometimes reaching significantly higher values. Aspartic acid is encoded in the genetic code by the codons GAU and GAC, and in the one-letter amino acid code is represented as D, chosen arbitrarily.

Discovery

Aspartic acid was first identified in 1827 by Auguste-Arthur Plisson and Étienne-Ossian Henry. The researchers obtained the compound through the hydrolysis of asparagine, itself isolated from asparagus juice in the early nineteenth century. Although lead hydroxide was used in their early protocol, contemporary methods employ alternative acidic or basic reagents to generate purer yields.

Forms and Nomenclature

Aspartic acid exists in two enantiomeric forms: L-aspartic acid and D-aspartic acid. The non-racemic, L-enantiomer is incorporated into proteins during translation, whereas the D-isomer appears in certain peptides, tissues and signalling pathways, particularly within mammalian nervous systems. Chemical synthesis methods often generate a DL-racemic mixture, while enzymatic pathways typically produce a single, enantiomerically pure form.

Synthesis

Biosynthesis

Aspartate is synthesised primarily via the transamination of oxaloacetate. An aminotransferase enzyme transfers an amino group from a donor molecule, often alanine or glutamine, yielding aspartate and a corresponding α-keto acid. This reaction integrates aspartate production into central metabolic processes, linking amino acid synthesis to the citric acid cycle.

Chemical and Industrial Synthesis

Industrial production commonly involves the amination of fumarate, catalysed by L-aspartate ammonia-lyase. For racemic mixtures, synthetic routes may employ compounds such as diethyl sodium phthalimidomalonate, which can be converted into aspartic acid through sequential chemical steps.

Metabolic Roles

Aspartate participates in several key metabolic pathways across plants, microorganisms and animals.

• In plants and microbes, aspartate is a precursor for several essential amino acids, including methionine, threonine, isoleucine and lysine. The first step involves reducing aspartate to its semialdehyde.
• Asparagine is formed from aspartate through transamidation, using glutamine or glutamic acid as the amide donor.
• Aspartate contributes a nitrogen atom to the biosynthesis of inosine, the purine precursor.
• It functions within the urea cycle and plays a role in gluconeogenesis.
• In the malate–aspartate shuttle, aspartate facilitates the transport of reducing equivalents across mitochondrial membranes by interconversion with oxaloacetate.
• Aspartic acid acts as a hydrogen acceptor within the proton-translocation mechanism of ATP synthase.

Dietary L-aspartic acid has also been shown to inhibit β-glucuronidase, an enzyme involved in enterohepatic circulation of bilirubin and bile acids.

Aspartate as a Neurotransmitter

Aspartate, in its ionic form, acts as an excitatory neurotransmitter. It is capable of stimulating NMDA receptors, though less potently than glutamate. The compound lends its name to the NMDA receptor through the synthetic agonist N-methyl-D-aspartate, used extensively in neurophysiological research.

Applications and Market Use

Aspartic acid plays an important role in numerous commercial and industrial products. As of 2014, the global market value was estimated at approximately US$117 million, with significant demand in the United States, Western Europe and China.
Key application areas include:

• Biodegradable polymers such as polyaspartic acid
• Low-calorie sweeteners, notably aspartame, synthesised from aspartic acid and phenylalanine
• Scale and corrosion inhibitors
• Resins and coating agents

One rapidly expanding sector is the production of biodegradable superabsorbent polymers (SAPs) and hydrogels, used primarily in absorbent hygiene products. Approximately three-quarters of SAPs are used in disposable nappies, with additional demand in products for adult incontinence and feminine hygiene. Polyaspartic acid offers an environmentally friendly alternative to polyacrylate-based polymers.
Aspartic acid also features in fertilisers, where polyaspartate polymers enhance water retention and nitrogen uptake in soils.

Dietary Sources

As a non-essential amino acid, aspartic acid does not require direct dietary intake for human health, since it can be synthesised endogenously from intermediates of central metabolism. Because roughly one in twenty amino acids within eukaryotic proteins is an aspartate residue, nearly all dietary protein sources supply measurable amounts.
Aspartic acid may also be consumed in salt forms such as magnesium aspartate. Its derivative, aspartame, used as a sweetener, contributes both phenylalanine and aspartic acid upon digestion.