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Written by Dr. Tom Shurlock for and on behalf of GWF Nutrition Limited. Published: May 2019.
Copyright: GWF Nutrition Limited - Not for Reproduction.
Described under EU register of feed additives, glutamic acid, or glutamate, is defined as a natural or corresponding synthetic chemically defined flavouring, alongside is its salt monosodium glutamate. However, glutamic acid has many more roles.
Glutamic acid is a non-essential amino acid, in that it can be synthesised by transamination of ketoglutarate and is one of the most prevalent amino acids in the body. Similarly, it can donate its amino group, releasing α-ketoglutarate which can enter the TCA cycle, and is a major route of oxidation and energy generation in the small intestine; glutamic acid has rapid turnover and a relatively low blood pool, as its utilisation is high. It was assumed that, due to its rapid metabolism, uptake by glutamate was limited to the liver and gut. However, its role as a neuroprotectant, excitatory molecule and taste stimulant (in the free form) are well documented.
Currently, there has been an addition to the classical four taste responses (sweet, bitter, sour, salt); a fifth, umani, has been described as a “savoury” response. There are three main components, which are activated through the receptors T1R1 + T1R3, mGluR4, and mGluR1, and involve glutamate (as the ion, sodium, calcium & potassium salts), 5’-inosinate, and 5’-guanylate; these latter are derived from the decomposition of ATP & RNA respectively as a result of cell death. Glutamate, however, stimulates a response in its free state; glutamic acid when protein bound has no taste. Free glutamate is a stable product and so can be incorporated into processed products with little deterioration. Dogs have been reported as having high synergy between the receptors that may explain their acceptance of savoury foods, but also a rejection of meat that is over decayed.
It has also been shown that dietary-free glutamate in the stomach interacts with specific glutamate receptors (T1R1/T1R3 and mGluR1–8) expressed on surface epithelial and gastric gland cells. Furthermore, luminal glutamate activates the vagal afferents in the stomach through the paracrine cascade including nitric oxide and serotonin (5-HT), both of which modulate gastric secretions and impact on hunger/satiety mechanisms.
Function in Small Intestine
Although glutamate has the highest concentration in the luminal peptides, it has the lowest in venous blood. This is largely because glutamate is extensively oxidized in small intestine epithelial cells during its transcellular journey from the lumen to the bloodstream and after its uptake from the bloodstream. Oxidative capacity coincides with a high energy demand of the epithelium, which is in rapid renewal and responsible for the nutrient absorption process. Dissociation to α-ketoglutarate is the mechanism to supply the energy.
Glutamate is also a precursor for glutathione and N-acetylglutamate in enterocytes. Glutathione is an antioxidant involved in moderating damage caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals . N-acetylglutamate is an activator of carbamoylphosphate synthetase 1, which is implicated in L-citrulline production by enterocytes; citrulline is central to the urea cycle. Glutamate is a precursor in enterocytes for several other amino acids, including L-alanine, L-aspartate, L-ornithine, and L-proline.
Intestinal epithelial cell capacity to oxidize glutamine and glutamate is high; in colonocytes, glutamate also serves as a fuel but is provided from the bloodstream. Alimentary and endogenous proteins that escape digestion enter the large intestine and are fermented by colonic bacterial flora, which then release free glutamate into the lumen. Glutamate can then serve in the colon lumen as a precursor for butyrate and acetate in bacteria. Glutamate, in addition to fibre and digestion-resistant starch, can thus serve as a luminally derived fuel precursor for colonocytes. Additionally, it enhances cell viability and membrane integrity by increasing the abundance of the tight junction proteins occludin, claudin-3, zonula occludens (ZO)-2, and ZO-3. As it also acts as a precursor for butyrate, colonocyte integrity, and hindgut cell tight junctions are also maintained.
One further product that glutamate is a precursor is ϒ-aminobutyric acid (GABA)
GABA is a nonstandard amino acid that acts as the principal inhibitory neurotransmitter in central nervous system (CNS) function. Up to 40% of all synapses in the CNS operate for GABA, and GABA receptors are found in every region of the brain. GABA systems are implicit in a number of neurophysiological processes, including motor function, pain, sleep, brain development and anxiety. Interacting with the endocannabinoid system, GABA also has an analgesic role in pain and inflammatory control; as such it also has modulatory actions with interleukin and tumour necrosis factors.
Glutamate is also the main excitatory neurotransmitter, its interaction with GABA being the basis of the balance between metabolic processes, and down regulating both excitatory and sedative processes. Neural glutamate activity is also modulated by other chemicals; arachidonic acid blocks glutamate uptake, serotonin modulates 3H-GA binding to receptors, and interleukin-1l-β and ϒ-neuropeptide all increase neuronal glutamate release.
Glutamate is a precursor of glutamine, a conditionally essential amino acid. Within amino acid biochemistry is the Glutamine-Glutamate-GABA shunt. This process supports glucose metabolism in the neurones, and in astrocytes (non-neurone cells in the brain & CNS) and so supports the interaction of the glutamate GABA control of neurotransmission. However, glutamine has a further role, in wound healing. Glutamine has shown epithelialisation with new blood vessel formation, decreased wound area, increased wound contraction & tensile strength and hydroxyproline content.
Although glutamic acid is a commonly occurring amino acid, it has an important role in neurotransmission, through its interaction with the metabolites, GABA and glutamine, and is also critical for gut health, oxidative protection and energy generation of the intestinal cells, As the free amino acid – as in supplementation - it provides gustatory stimulation (improves taste through the umani receptors) as well as modulating gastric secretions. This latter “prepares” the gut for the oncoming food as is therefore integral across gut function.
Because of the range of effects, where supplementation by glutamic acid can be of benefit, GWF Nutrition have added it across their range of products, Inflammatory interaction, gut health and specialist feeds (e.g. Hembra & Cria) all benefit from gustatory and absorptive support, as supplied by glutamic acid.
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