Glutamic acid

Glutamic acid, symbol Glu or E, is a naturally occurring amino acid used by almost all living organisms in the biosynthesis of proteins. In its anionic form it is known as glutamate, a term widely applied in biochemical and nutritional contexts. It is a non-essential amino acid for humans, as the body can synthesise sufficient quantities for its metabolic needs. Beyond its role in proteins, glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system and serves as a precursor for the inhibitory neurotransmitter γ-aminobutyric acid (GABA). It contributes to the flavour of foods through the characteristic savoury taste known as umami and is present naturally in a wide range of dietary sources.

Chemical structure and properties

Glutamic acid has the molecular structure HOOC-CH₂-CH₂-COOH with two carboxylic acid groups and one amine group. The compound has two optically active isomers arising from a chiral centre. In the solid state and in mildly acidic aqueous solutions, it exists predominantly as a zwitterion, in which the amine group is protonated and one carboxyl group is deprotonated.
The amino acid is encoded in the genetic code by the codons GAA and GAG. In aqueous solution, its ionisation state varies with pH. In strongly acidic environments both carboxyl groups are protonated, yielding a positively charged species. Between pH values of approximately 2.5 and 4.1 the molecule exists mainly as a neutral zwitterion. At physiological pH (around 7.35–7.45), glutamate carries a single negative charge as one carboxylate group has lost a proton. At very high pH values, the amine group loses its proton and the molecule becomes a doubly negatively charged anion. The radical derived from glutamate is known as glutamyl.
The one-letter symbol E follows D for aspartic acid, reflecting the structural difference of an additional methylene (CH₂) group.

Optical isomerism

Two enantiomeric forms of glutamic acid exist: L-glutamic acid and D-glutamic acid. The L-form is the one commonly found in proteins and is the biologically predominant form. The D-form, although rare in higher organisms, appears in specific biological contexts. Certain bacteria incorporate D-glutamate into their cell walls via the action of the enzyme glutamate racemase. D-glutamate can also occur in microflora of the intestinal tract and in some foods. Unlike many other amino acids, glutamate is not readily oxidised by amino acid oxidases and undergoes limited deamination when ingested.
Glutamate occurs in free form at surprisingly high levels in mammalian tissues. In the liver, free glutamate accounts for a significant fraction of total glutamate and acts as a potent inhibitor of glutathione synthesis. Some aquatic species, such as particular eels, use glutamate as a pheromone for chemical signalling.

History

Although glutamic acid occurs naturally in food, its flavour-enhancing properties were only systematically identified in the early twentieth century. The compound was first isolated in 1866 by the German chemist Karl Heinrich Ritthausen, who extracted it by treating wheat gluten with sulphuric acid. In 1908, Kikunae Ikeda of Tokyo Imperial University identified glutamic acid crystals as the source of a distinctive taste present in seaweed broth. He termed the flavour umami, recognising it as distinct from the traditional basic tastes. Ikeda later developed and patented a method for producing monosodium glutamate (MSG), the widely used flavour enhancer.

Synthesis and production

BiosynthesisIn human metabolism, glutamate arises primarily from transamination reactions. The amino group of another amino acid is transferred to α-ketoglutarate, a central intermediate of the citric acid cycle, forming glutamate. This reaction is catalysed by transaminases and is crucial for amino acid interconversion. Glutamate can also undergo oxidative deamination by glutamate dehydrogenase, producing α-ketoglutarate and ammonia, thereby linking amino acid degradation with nitrogen disposal through urea synthesis.
Industrial synthesisGlutamic acid is one of the most extensively produced amino acids. Industrial manufacture shifted in the 1950s from chemical synthesis to aerobic fermentation. Microorganisms such as Corynebacterium glutamicum convert sugars and ammonia into glutamic acid on a large scale. The global annual production in the early twenty-first century was estimated in excess of one million tonnes. Purification is achieved by concentration and crystallisation, and the compound is also marketed in the form of its hydrochloride salt.

Metabolic functions

Glutamate plays a central role in cellular metabolism. It participates in:

• Transamination reactions, which allow the transfer of nitrogen between amino acids and carbon skeletons.
• Nitrogen metabolism, serving as an intermediary in the removal of amino groups through deamination.
• Energy production, via its direct relationship with α-ketoglutarate and the citric acid cycle.
• Biosynthesis, providing nitrogen for the synthesis of other amino acids and biomolecules.

Pyruvate and oxaloacetate, which are produced alongside glutamate in specific transamination reactions, are important intermediates in pathways such as glycolysis, gluconeogenesis, and the citric acid cycle. Glutamate’s role in linking transamination and deamination makes it a primary conduit for nitrogen flow through metabolic pathways.
Malignant brain tumours, notably gliomas and glioblastomas, may exploit glutamate as an energy source. Mutations in genes such as IDH1 can increase tumour dependence on glutamate, facilitating growth and metabolic adaptation.

Neurotransmitter function

In vertebrates, glutamate is the chief excitatory neurotransmitter. It is concentrated in synaptic vesicles and released by presynaptic neurons in response to electrical impulses. Glutamate activates both ionotropic receptors, which are ligand-gated ion channels, and metabotropic receptors, which are G-protein-coupled. These receptors mediate fast synaptic transmission and modulate numerous cognitive and motor functions.
Proper regulation of glutamate signalling is essential for neural health. Excessive stimulation can lead to excitotoxicity, a pathological process implicated in several neurological disorders. Glutamate also serves as the immediate precursor to GABA, the principal inhibitory neurotransmitter, through the action of glutamic acid decarboxylase in GABAergic neurons.

Role in flavour and food applications

The glutamate anion contributes the characteristic umami taste found in foods such as seaweed, soy products, meats, and aged cheeses. Food industries utilise glutamate in the form of monosodium glutamate (MSG) to enhance savoury flavour. Within European regulation, glutamate salts are assigned E-numbers and are approved for use as food additives. The compound’s ability to intensify taste arises from binding to specific receptors on the tongue that detect umami.
Glutamic acid and its derivatives are therefore important not only in metabolism and neuroscience but also in culinary science and industrial food production.