Free Glutamate Research Articles

1H NMR Metabolite Fingerprint and Pattern Recognition of Mullet (Mugil cephalus) Bottarga

Nuclear magnetic resonance (NMR) spectroscopy combined with multivariate data analysis (MVA) was used to investigate the molecular components of the aqueous extract of samples of bottarga, that is, salted and dried mullet (Mugil cephalus) roe, manufactured in Sardinia (Italy) from mullets of known and unknown geographical provenience. Principal component analysis (PCA) applied to the processed (1)H NMR spectra indicated that samples tend to cluster according to their geographical origin and also on the basis of storage and manufacturing procedures. The most important metabolites that characterized grouping of samples are the free amino acids methionine (Met), glutamate (Glu), histidine (His), phenylalanine (Phe), tyrosine (Tyr), and isoleucine (Ile); trimethylamine (TMA) and dimethylamine (DMA), both biomarkers of degradation; nucleotides and derivatives; choline (Cho) and phosphorylcholine (P-cho); and lactate (Lac).

Dietary free glutamate prevents diarrhoea during intra-gastric tube feeding in a rat model

Recent studies indicate that l-glutamate (l-Glu), abundant in many foods, is a stimulator of gastric vagal afferent nerves. The aim of the present study was to examine the possibility that l-Glu supplementation of a protein-rich liquid diet may prevent the incidence of diarrhoea during repetitive intra-gastric tube feeding. The gastric vagal afferent nerve recording of rats indicated that intra-gastric administration of a protein-rich liquid diet supplemented with 0·5% monosodium glutamate enhanced the basal afferent activities seen with the protein-rich diet alone. The examination of the faeces showed that the addition of monosodium glutamate to the liquid diet significantly prevented the incidence of diarrhoea induced by repetitive gastric feeding. In conclusion, supplementation of an enteral liquid diet with free l-Glu may ameliorate diarrhoea during intra-gastric tube feeding by sending visceral glutamate information from the stomach to the brain.

N-Acetylaspartylglutamate Synthetase II Synthesizes N-Acetylaspartylglutamylglutamate

N-Acetylaspartylglutamate (NAAG) is found at high concentrations in the vertebrate nervous system. NAAG is an agonist at group II metabotropic glutamate receptors. In addition to its role as a neuropeptide, a number of functions have been proposed for NAAG, including a role as a non-excitotoxic transport form of glutamate and a molecular water pump. We recently identified a NAAG synthetase (now renamed NAAG synthetase I, NAAGS-I), encoded by the ribosomal modification protein rimK-like family member B (Rimklb) gene, as a member of the ATP-grasp protein family. We show here that a structurally related protein, encoded by the ribosomal modification protein rimK-like family member A (Rimkla) gene, is another NAAG synthetase (NAAGS-II), which in addition, synthesizes the N-acetylated tripeptide N-acetylaspartylglutamylglutamate (NAAG(2)). In contrast, NAAG(2) synthetase activity was undetectable in cells expressing NAAGS-I. Furthermore, we demonstrate by mass spectrometry the presence of NAAG(2) in murine brain tissue and sciatic nerves. The highest concentrations of both, NAAG(2) and NAAG, were found in sciatic nerves, spinal cord, and the brain stem, in accordance with the expression level of NAAGS-II. To our knowledge the presence of NAAG(2) in the vertebrate nervous system has not been described before. The physiological role of NAAG(2), e.g. whether it acts as a neurotransmitter, remains to be determined.

Engineered pH-Dependence at the Kir6.2 Helix Bundle Crossing

The hallmark functional property of KATP (ATP-sensitive potassium) channels is inhibition by intracellular ATP, which binds to a well-defined binding site on Kir6.x subunits and stabilizes the closed conformation of a gate in the channel pore. Numerous inwardly-rectifying potassium (Kir) channels possess an aromatic residue in the ‘helix bundle crossing’ region, forming the narrowest pore constriction in crystal structures of Kir channels, indicating an important role in channel gating. We have identified a remarkable phenotype of mutant channels carrying a glutamate at this position (F168E). Despite the structural prediction of four glutamates in close proximity, F168E channels are predominantly closed at physiological pH. However, intracellular alkalinization causes rapid and reversible channel activation. These findings suggest that F168E glutamates are uncharged at physiological pH but become deprotonated with a pKa∼9, resulting in opening due to mutual repulsion of multiple nearby glutamate sidechains. The K-channel pore scaffold likely brings these glutamates into close proximity, stabilizing the protonated (uncharged) form of the glutamate sidechain, and resulting in a dramatic pKa shift relative to free glutamate. Only at more alkaline pH do the glutamates deprotonate, with their mutual repulsion driving channel opening. Consistent with a role in ATP-mediated channel closure, alkalinization also affects channel sensitivity to ATP. Taken together, these findings demonstrate an engineered (not intrinsic) mechanism of channel gating by pH, and suggest that ATP-mediated gating of Kir6.2 involves conformational rearrangement of the bundle crossing region.

Hetero-oligomerization of Neuronal Glutamate Transporters

Excitatory amino acid transporters (EAATs) mediate the uptake of glutamate into neuronal and glial cells of the mammalian central nervous system. Two transporters expressed primarily in glia, EAAT1 and EAAT2, are crucial for glutamate homeostasis in the adult mammalian brain. Three neuronal transporters (EAAT3, EAAT4, and EAAT5) appear to have additional functions in regulating and processing cellular excitability. EAATs are assembled as trimers, and the existence of multiple isoforms raises the question of whether certain isoforms can form hetero-oligomers. Co-expression and pulldown experiments of various glutamate transporters showed that EAAT3 and EAAT4, but neither EAAT1 and EAAT2, nor EAAT2 and EAAT3 are capable of co-assembling into heterotrimers. To study the functional consequences of hetero-oligomerization, we co-expressed EAAT3 and the serine-dependent mutant R501C EAAT4 in HEK293 cells and Xenopus laevis oocytes and studied glutamate/serine transport and anion conduction using electrophysiological methods. Individual subunits transport glutamate independently of each other. Apparent substrate affinities are not affected by hetero-oligomerization. However, polarized localization in Madin-Darby canine kidney cells was different for homo- and hetero-oligomers. EAAT3 inserts exclusively into apical membranes of Madin-Darby canine kidney cells when expressed alone. Co-expression with EAAT4 results in additional appearance of basolateral EAAT3. Our results demonstrate the existence of heterotrimeric glutamate transporters and provide novel information about the physiological impact of EAAT oligomerization.

Free Glutamate Content of Condiment and Seasonings and Their Intake in Bogor and Jakarta, Indonesia

Free glutamate has been known as flavor enhancer. Commercially, free glutamate is available in form of monosodium glutamate (MSG) crystal. Seasoning or premix may also contain free glutamate or MSG. The aim of the present study was focus on the determination of the usage and potential/actual exposure of consumers to free glutamate from condiment and seasonings. There were several steps of the study, i.e. survey, laboratory analyses, data analyses, and evaluation of total exposure of free glutamate from condiment and seasonings. The survey was conducted to the 110 households in Bogor (rural) and 112 households in Jakarta (urban). The samples of condiment/seasoning were analyzed by using high performance liquid chromatography (HPLC) with fluorescent detector. The condiment/seasonings were categorized into 15 types, i.e. sweet soy sauce, salty soy sauce, fermented soybean paste, tomato sauce, MSG, premix seasoning, fermented fish/shrimp paste, chili sauce, ready to use seasoning, seasoned flour, dip and sauce, mayonnaise and mustard, spread, oyster and fish sauce, and teriyaki and others. The results of condiment/seasonings survey revealed that sweet soy sauce, MSG, and premix seasoning were used by most of households (±71% or more than 80 households) both in Bogor and Jakarta. The laboratory analyses of free glutamate from condiment/seasonings revealed that the highest free glutamate content was found in MSG (733.29 mg/g). Beside MSG, there were three other condiments that also had high free glutamate content, i.e. premix seasoning (70.77 mg/g in Bogor and 63.66 mg/g in Jakarta), oyster and fish sauce (46.76 mg/g in Bogor), and ready to use seasoning (15.71 mg/g in Jakarta). Although the average condiment/seasonings usage in Bogor (5.39 g/cap/day) was lower than that in Jakarta (9.62 g/cap/day), but the free glutamate intake from condiment/seasonings in Bogor (847.04 mg/cap/day) was higher than that in Jakarta (615.87 mg/cap/day). This was due to the high contribution of MSG that used in higher amount in Bogor.

Excrescence of neurotransmitter glutamate from disc material has nociceptive qualities: evidence from a rat model

Background context The authors have previously demonstrated that herniated human lumbar disc is rich in free glutamate from degradation of aggrecan. Prior data have suggested that free glutamate could contribute to a nociceptive state. Purpose Previous behavioral experiments suggested glutamate-related nociception by comparing pre- and postglutamate infusion responses only. This indirectly suggested nociceptive effects of epidural glutamate but was not a definitive evidence. Now, by using larger numbers of subjects, we have demonstrated that lumbar epidural glutamate infusion causes significant left-to-right differences in hind paw response during treatment, demonstrating more directly the focal nociceptive effects of glutamate. Study design Behavioral studies and immunohistochemistry were used to assess for evidence of a nociceptive state. All researchers were blinded to infusion solution. Methods Via an implanted mini osmotic pump, the epidural space of rats was infused with 0.02 mM glutamate or normal saline for 72 hours. Signs of nociception were assessed by von Frey and plantar thermal stimulation testing and by glutamate receptor expression in the corresponding dorsal horn of the spinal cord and dorsal root ganglion. Results Both von Frey mechanical and plantar thermal stimulations showed differences in hind paw reactivity depending on whether it was on the ipsilateral or contralateral side of glutamate infusion. Saline infusion had no significant behavioral effects. Dorsal horn expression of 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid and N-methyl- d-aspartic acid receptors was significantly increased in glutamate-infused animals, further indicative of a nociceptive state related to glutamate infusion. Conclusions Elevated epidural glutamate concentrations caused a focal hyperesthetic state. Increased epidural glutamate concentration could be a driving force or “chemical” component of disc-related radiculopathy.

Molecular Identification of N-Acetylaspartylglutamate Synthase and β-Citrylglutamate Synthase

The purpose of the present work was to determine the identity of the enzymes that synthesize N-acetylaspartylglutamate (NAAG), the most abundant dipeptide present in vertebrate central nervous system (CNS), and β-citrylglutamate, a structural analogue of NAAG present in testis and immature brain. Previous evidence suggests that NAAG is not synthesized on ribosomes but presumably is synthesized by a ligase. As attempts to detect this ligase in brain extracts failed, we searched the mammalian genomes for putative enzymes that could catalyze this type of reaction. Mammalian genomes were found to encode two putative ligases homologous to Escherichia coli RIMK, which ligates glutamates to the C terminus of ribosomal protein S6. One of them, named RIMKLA, is almost exclusively expressed in the CNS, whereas RIMKLB, which shares 65% sequence identity with RIMKLA, is expressed in CNS and testis. Both proteins were expressed in bacteria or HEK293T cells and purified. RIMKLA catalyzed the ATP-dependent synthesis of N-acetylaspartylglutamate from N-acetylaspartate and l-glutamate. RIMKLB catalyzed this reaction as well as the synthesis of β-citrylglutamate. The nature of the reaction products was confirmed by mass spectrometry and NMR. RIMKLA was shown to produce stoichiometric amounts of NAAG and ADP, in agreement with its belonging to the ATP-grasp family of ligases. The molecular identification of these two enzymes will facilitate progress in the understanding of the function of NAAG and β-citrylglutamate.

Rapid modification of the insect elicitor N-linolenoyl-glutamate via a lipoxygenase-mediated mechanism on Nicotiana attenuata leaves

BackgroundSome plants distinguish mechanical wounding from herbivore attack by recognizing specific constituents of larval oral secretions (OS) which are introduced into plant wounds during feeding. Fatty acid-amino acid conjugates (FACs) are major constituents of Manduca sexta OS and strong elicitors of herbivore-induced defense responses in Nicotiana attenuata plants.ResultsThe metabolism of one of the major FACs in M. sexta OS, N-linolenoyl-glutamic acid (18:3-Glu), was analyzed on N. attenuata wounded leaf surfaces. Between 50 to 70% of the 18:3-Glu in the OS or of synthetic 18:3-Glu were metabolized within 30 seconds of application to leaf wounds. This heat-labile process did not result in free α-linolenic acid (18:3) and glutamate but in the biogenesis of metabolites both more and less polar than 18:3-Glu. Identification of the major modified forms of this FAC showed that they corresponded to 13-hydroxy-18:3-Glu, 13-hydroperoxy-18:3-Glu and 13-oxo-13:2-Glu. The formation of these metabolites occurred on the wounded leaf surface and it was dependent on lipoxygenase (LOX) activity; plants silenced in the expression of NaLOX2 and NaLOX3 genes showed more than 50% reduced rates of 18:3-Glu conversion and accumulated smaller amounts of the oxygenated derivatives compared to wild-type plants. Similar to 18:3-Glu, 13-oxo-13:2-Glu activated the enhanced accumulation of jasmonic acid (JA) in N. attenuata leaves whereas 13-hydroxy-18:3-Glu did not. Moreover, compared to 18:3-Glu elicitation, 13-oxo-13:2-Glu induced the differential emission of two monoterpene volatiles (β-pinene and an unidentified monoterpene) in irlox2 plants.ConclusionsThe metabolism of one of the major elicitors of herbivore-specific responses in N. attenuata plants, 18:3-Glu, results in the formation of oxidized forms of this FAC by a LOX-dependent mechanism. One of these derivatives, 13-oxo-13:2-Glu, is an active elicitor of JA biosynthesis and differential monoterpene emission.

Glutamate Decarboxylase-Mediated Nisin Resistance in Listeria monocytogenes

Analysis of a complete set of glutamate decarboxylase (gad) mutants of Listeria monocytogenes strain LO28 (ΔgadD1, ΔgadDT1, ΔgadD2, ΔgadT2, and ΔgadD3 mutants) revealed that the ΔgadD1 mutant is impaired in its ability to tolerate exposure to both sublethal and lethal levels of the lantibiotic nisin. gadD1 is strain variable and is found only in approximately 50% of L. monocytogenes strains. Growth and survival experiments revealed that possession of gadD1 correlates with a higher degree of tolerance to nisin. Significantly, a similar finding using a gadB mutant of L. lactis IL1403 implies that this may be a general phenomenon in Gram-positive bacteria. Our findings thus suggest that the specific inhibition of GAD activity or a reduction in the levels of free glutamate may prevent the growth of otherwise resistant GAD(+) bacteria in foods where low pH and/or nisin is used as a preservative.

Glutamate determination in foodstuffs with a very simple HPLC-UV method

To date, monosodium glutamate is the most used flavour enhancing food additive. Because high levels of glutamate are toxic to brain concerns appeared regarding the safe use of glutamate and there is a 10 g kg −1 concentration limit in foodstuff. A simple HPLC-UV method, based on a derivatization procedure with o -phthaldialdehyde, was developed for determination of glutamate in meat products, soup bases and vegetable concentrates. Even if our method is less sensitive than the HPLC-fluorescence ones widely available, it is able to measure amounts at least 200 times smaller than the maximum allowed one, has good reproducibility (CV under 2% for intraday and under 3% for interday determinations), linearity and accuracy. Less expensive HPLC systems are required and the formed derivative is very stable (at least 1 week), good separation is obtained with the less expensive 5 μm particle C 18 columns and methanol as organic phase. Concentration of free glutamate ranged between 0.14 g kg −1 in sausage without added glutamate to as high as 2.16 g kg −1 in a pork sausage. Concentration in vegetable mixes and soup bases were between 80–120 g kg −1 .

Urinary Metabolic Phenotyping Differentiates Children with Autism from Their Unaffected Siblings and Age-Matched Controls

Autism is an early onset developmental disorder with a severe life-long impact on behavior and social functioning that has associated metabolic abnormalities. The urinary metabolic phenotypes of individuals (age range=3-9 years old) diagnosed with autism using the DSM-IV-TR criteria (n = 39; male = 35; female = 4), together with their nonautistic siblings (n = 28; male = 14; female = 14) and age-matched healthy volunteers (n = 34, male = 17; female = 17) have been characterized for the first time using (1)H NMR spectroscopy and pattern recognition methods. Novel findings associated with alterations in nicotinic acid metabolism within autistic individuals showing increased urinary excretion of N-methyl-2-pyridone-5-carboxamide, N-methyl nicotinic acid, and N-methyl nicotinamide indicate a perturbation in the tryptophan-nicotinic acid metabolic pathway. Multivariate statistical analysis indicated urinary patterns of the free amino acids, glutamate and taurine were significantly different between groups with the autistic children showing higher levels of urinary taurine and a lower level of urinary glutamate, indicating perturbation in sulfur and amino acid metabolism in these children. Additionally, metabolic phenotype (metabotype) differences were observed between autistic and control children, which were associated with perturbations in the relative patterns of urinary mammalian-microbial cometabolites including dimethylamine, hippurate, and phenyacetylglutamine. These biochemical changes are consistent with some of the known abnormalities of gut microbiota found in autistic individuals and the associated gastrointestinal dysfunction and may be of value in monitoring the success of therapeutic interventions.

Amino acids and minerals in ancient remnants of fish sauce (garum) sampled in the “Garum Shop” of Pompeii, Italy

Savory (umami) condiments are widely used throughout the world to enhance taste properties of some foods. Archeological research has indicated that the use of such condiments, notably high quality fish sauces (garum), might have been extensive already in the ancient Roman Empire; however, little is known about the biochemical composition of garum. The aim of this study was to sample remnants of garum from preserved containers (dolia) located in Pompeii, evaluate concentrations of free amino acids, and compare them to those of modern fish sauces produced in southern Italy and southeast Asia. In spite of significant degradation of amino acids, analysis of remnants from ancient garum confirmed a pattern of free amino acids that was comparable to the pattern detected in modern Italian and Asian products, with free glutamate being the taste-dominant amino acid, followed by sweet-tasting glycine and alanine. Since the above free amino acids are the determining taste substances in savory sauces, the present finding indicates that Romans in the first century AD enjoyed umami condiments with taste profiles paralleling those of modern Asian fish sauces. If technology transfers from Europe to Asia could be documented by archeological means, this study would be the first indication of an early “globalization” in food taste preferences.

GLUTAMATE SUPPRESSES HELICOBACTER PYLORI‐INDUCED GASTRIC ATROPHY ‐MECHANISMS OF CHIEF CELL PROTECTION

Luminal free glutamate (Glu) induces gastroduodenal mucus secretion, suggesting the protective roles of dietary free Glu during digestion process. We have previously reported that Glu supplemented in the diet reduces Helicobacter pylori (HP)‐induced gastric mucosal damages in gerbils. Surprisingly, gastric atrophy (i.e. the loss of pepsinogen‐secreting chief cells and acid‐secreting parietal cells) was also reduced by Glu supplementation. To clarify the mechanisms how Glu reduces gastric atrophy against HP, we investigated the direct protective role of Glu on the cell viability of cultured chief cells against ammonia, a known HP toxin. NH4Cl (an ammonia donor) significantly reduced cell viability. Glu, glutamine, asparagine and aspartate all protected cultured chief cells against NH4Cl. Pharmacological analysis revealed that Glu synthetase inhibitors, L‐methionine sulfoximine and L‐2‐amino adipic acid protected chief cells against NH4Cl‐induced cell death. In contrast, glutathione synthetase inhibitor, L‐buthionine sulfoximine had no effect on Glu‐induced chief cell protection against NH4Cl. These results suggest that Glu reduces HP‐induced gastric atrophy partly via glutamine synthetase‐mediated pathway. Thus, we propose that free Glu in the diet would contribute to the protection from gastric atrophy against HP in daily life.

New Frontiers in Gut Nutrient Sensor Research: Monosodium l-Glutamate Added to a High-Energy, High-Protein Liquid Diet Promotes Gastric Emptying: a Possible Therapy for Patients With Functional Dyspepsia

Functional dyspepsia is a clinical syndrome that features abdominal symptoms centered in the upper abdomen without an organic basis. Three possible mechanisms of gastric dysfunction could be related to functional dyspepsia: 1) delayed gastric emptying, 2) impaired gastric accommodation to food intake, and 3) hypersensitivity to gastric distention. Delayed gastric emptying has been suggested to lead to prolonged antral distension that causes dyspeptic symptoms. Delayed gastric emptying is therefore a focal point of debate about anorexia caused by dyspepsia, and prokinetic agents are often administered in Japan for its treatment. Recently, we found that addition of monosodium l-glutamate (MSG) to a high-energy liquid diet rich in casein promoted gastric emptying in healthy men. Therefore, another potential method to improve delayed gastric emptying could be enhancement of chemosensors that activate the autonomic nervous system innervating the gastrointestinal tract. In conclusion, enrichment with glutamate promoted gastric emptying after intake of a high-protein meal, suggesting that free glutamate is important for protein digestion and that MSG may be helpful for management of delayed gastric emptying in patients with functional dyspepsia.

Pathogenesis, neuroimaging and management in children with cerebral palsy born preterm.

With advances in obstetric and perinatal management, the incidence of intraventricular hemorrhage in premature infants has declined, while periventricular leukomalacia remains a significant concern. It is now known that brain injury in children born preterm also involves neuronal-axonal disease in supratentorial and infratentorial structures. The developing brain is especially vulnerable to white matter (WM) injury from 23 to 34 weeks gestation when blood vessels serving the periventricular WM are immature. Oligodendrocyte progenitors, which are beginning to form myelin during this time, are susceptible to attack from oxygen free radicals, glutamate, and inflammatory cytokines. Advances in imaging techniques such as diffusion tensor imaging provide a more complete picture of the location and extent of injury. Effective management of children born preterm with cerebral palsy is predicated on an understanding of sequential links from etiological antecedents to brain neuropathology as revealed with neuroimaging techniques to clinical phenotypes, toward focused interventions with measurable outcomes.

New Frontiers in Gut Nutrient Sensor Research: Luminal Glutamate–Sensing Cells in Rat Gastric Mucosa

Dietary free glutamate is known to elicit umami, one of the five basic tastes percepted via the specific taste sensor cells on the tongue. Recent studies suggest the specific glutamate sensors exist in the gastric mucosa and contribute to the regulation of gastrointestinal functions, yet the precise mechanism remains still unknown. We established the method to enrich various cell fractions from the isolated rat gastric mucosa and characterized the expression of putative glutamate sensors using such cell fractions. The gastric mucosal cell fractions such as surface mucous, parietal, chief, and endocrine cells were successfully prepared by mucosal protease digestion, elutriation, and gradient centrifugation. The characteristics of these cells were confirmed by real-time RT-PCR using the respective cell-specific markers. Parietal cell fraction exclusively expressed putative umami receptor molecules such as T1R1 and mGluR1 compared to other fractions, although the degree of expression was low. In contrast, the representative taste cell specific markers such as PLCβ2 and TRPM5 were specifically expressed in the smaller endocrine cell fraction. Both parietal and smaller endocrine cell fractions also positively expressed some mGluR subtypes. The chief-cell fraction less expressed T1R1 and mGluR1. These results suggest that multiple glutamate sensors, probably different mechanisms from taste buds, contribute to the glutamate sensing in the gastric mucosa.

A fast ruthenium polypyridine cage complex photoreleases glutamate with visible or IR light in one and two photon regimes

We introduce a new caged glutamate, based in a ruthenium bipyridyl core, that undergoes heterolytic cleavage after irradiation with visible light with wavelengths up to 532nm, yielding free glutamate in less than 50ns. Glutamate photorelease occurs also efficiently following two-photon (2P) excitation at 800nm, and has a functional cross section of 0.14GM.

Patterns of free amino acids in German convenience food products: marked mismatch between label information and composition

Free amino acids affect food palatability. As information on amino acids in frequently purchased pre-packaged food is virtually absent, we analyzed free amino acid patterns of 17 frequently purchased ready-to-serve convenience food products, and compared them with the information obtained from the respective food labels. Quantitative amino acid analysis was performed using ion-exchange chromatography. gamma-Aminobutyric acid (GABA) concentrations were verified using a stable isotope dilution gas chromatography/mass spectrometry (GC-MS) method. The patterns of free amino acids were compared with information obtained from food labels. An obvious mismatch between free amino acid patterns and food label information was detected. Even on considering that tomatoes and cereal proteins are naturally rich in glutamate, the concentrations of free glutamate outranged the natural concentration of this amino acid in several products, and strongly suggested artificial enrichment. Free glutamate was found to be elevated even in dishes that explicitly state 'no glutamate added'. Arginine was markedly elevated in lentils. Free cysteine was generally low, possibly reflecting thermal destruction of this amino acid during food processing. The meat and brain-specific dipeptide carnosine (CARN) was present in most meat-containing products. Some products did not contain detectable amounts of CARN in spite of meat content being claimed on the food labels. We detected GABA at concentrations that contribute significantly to the taste sensation. This investigation highlights a marked mismatch between food label information and food composition.

Metabolic fate and function of dietary glutamate in the gut

Glutamate is a main constituent of dietary protein and is also consumed in many prepared foods as an additive in the form of monosodium glutamate. Evidence from human and animal studies indicates that glutamate is a major oxidative fuel for the gut and that dietary glutamate is extensively metabolized in first pass by the intestine. Glutamate also is an important precursor for bioactive molecules, including glutathione, and functions as a key neurotransmitter. The dominant role of glutamate as an oxidative fuel may have therapeutic potential for improving function of the infant gut, which exhibits a high rate of epithelial cell turnover. Our recent studies in infant pigs show that when glutamate is fed at higher (4-fold) than normal dietary quantities, most glutamate molecules are either oxidized or metabolized by the mucosa into other nonessential amino acids. Glutamate is not considered to be a dietary essential, but recent studies suggest that the level of glutamate in the diet can affect the oxidation of some essential amino acids, namely leucine. Given that substantial oxidation of leucine occurs in the gut, ongoing studies are investigating whether dietary glutamate affects the oxidation of leucine in the intestinal epithelial cells. Our studies also suggest that at high dietary intakes, free glutamate may be absorbed by the stomach as well as the small intestine, thus implicating the gastric mucosa in the metabolism of dietary glutamate. Glutamate is a key excitatory amino acid, and metabolism and neural sensing of dietary glutamate in the developing gastric mucosa, which is poorly developed in premature infants, may play a functional role in gastric emptying. These and other recent reports raise the question as to the metabolic role of glutamate in gastric function. The physiologic significance of glutamate as an oxidative fuel and its potential role in gastric function during infancy are discussed.