Glutamic acid is metabolized in the tissues by oxidative deamination ... or by transamination with pyruvate to yield oxaloacetic acid ... which, via alpha-ketoglutarate, enters the citric acid cycle ... .. Quantitatively minor but physiologically important pathways of glutamate metabolism involve decarboxylation to gamma-aminobutyrate (GABA) and amidation to glutamine ... . Decarboxylation to GABA is dependent on pyridoxal phosphate, a coenzyme of glutamic acid decarboxylase ..., as is glutamate transaminase. Vitamin B6-deficient rats have elevated serum glutamate levels and delayed glutamate clearance ... . /Glutamic acid/
Oral dose of 1 g/kg monosodium glutamate given to rats was followed by only a small rise in plasma pyroglutamate levels. No incr of pyroglutamate or glutamate brain levels was observed under these conditions.
Monosodium glutamate (MSG) administered intraperitoneally /for 10 days/ at a dose of 4 mg/g bw markedly increase malondialdehyde (MDA) formation in the liver, the kidney and brain of rats. Simultaneous administration of VIT C, VIT E and quercetin to MSG-treated rats significantly reduced this increase in MDA induced by MSG. VIT E reduced lipid peroxidation mostly in the liver followed by VIT C and then quercetin, while VIT C and quercetin showed a greater ability to protect the brain from membrane damage than VIT E. The decreased glutathione (GSH) level elicited by MSG in the three organs corresponded with marked increase in the activity of glutathione-S-transferase (GST). While MSG increased (p < 0.001) the activities of superoxide dismutase and catalase in the liver, it decreased significantly the activities of these enzymes in the kidney and the brain. The three antioxidants were effective at ameliorating the effects of MSG on GSH levels and the enzymes in the three organs examined. While MSG increased the activity of glucose-6-phosphatase in the liver and kidneys of rats (p < 0.001), the activity of the enzyme was abysmally low in the brain. There were marked increases in the activities of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase in rats treated with MSG. The antioxidants tested protected against MSG-induced liver toxicity significantly. MSG at a dose of 4 mg/g significantly (p < 0.01) induced the formation of micronucleated polychromatic erythrocytes (MNPCEs). Co-treatment of rats with VIT C and quercetin inhibited the induction of MNPCEs by MSG (p < 0.001) ...
L-Glutamic acid and its ammonium, calcium, monosodium and potassium salts were evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1988. The Committee noted that intestinal and hepatic metabolism results in elevation of levels in systemic circulation only after extremely high doses given by gavage (>30mg/kg body weight). Ingestion of monosodium glutamate (MSG) was not associated with elevated levels in maternal milk, and glutamate did not readily pass the placental barrier. Human infants metabolized glutamate similarly to adults. Conventional toxicity studies using dietary administration of MSG in several species did not reveal any specific toxic or carcinogenic effects nor were there any adverse outcomes in reproduction and teratology studies. Attention was paid to central nervous system lesions produced in several species after parenteral administration of MSG or as a consequence of very high doses by gavage. Comparative studies indicated that the neonatal mouse was most sensitive to neuronal injury; older animals and other species (including primates) were less so. Blood levels of glutamate associated with lesions of the hypothalamus in the neonatal mouse were not approached in humans even after bolus doses of 10 g MSG in drinking water. Because human studies failed to confirm an involvement of MSG in "Chinese Restaurant Syndrome" or other idiosyncratic intolerance, the JECFA allocated an "acceptable daily intake (ADI) not specified" to glutamic acid and its salts. No additional risk to infants was indicated. The Scientific Committee for Food (SCF) of the European Commission reached a similar evaluation in 1991. The conclusions of a subsequent review by the Federation of American Societies for Experimental Biology (FASEB) and the Federal Drug Administration (FDA) did not discount the existence of a sensitive subpopulation but otherwise concurred with the safety evaluation of JECFA and the SCF.
/SRP Idiosyncratic reaction/: No decontamination measures have been reported. No antidotes exist. Supportive measures: Follow with ECG and cardiac evaluation if chest pain persists. Alert patient to avoid foods with MSG.
/HUMAN EXPOSURE STUDIES/ ... A high dose of 2.5 g was tested in 6 healthy controls and 30 asthmatics (7: allergic asthma; 15: intrinsic asthma with intolerance to aspirin; 8: intrinsic asthma with aspirin intolerance, intolerance to alcohol or to food additives). Two patients presented with a mild bronchospasm, occurring 6 to 10 hours after the ingestion. Different mechanisms are discussed. A cholinergic mechanism might be incriminated, either due to stimulation of the synthesis of acetylcholine, or due to a vagal reflex elicited by a reflux esophagitis. However, a high vagal hyperreactivity seems to be needed for the occurrence of asthma. It is concluded that a very small subset of patients with intrinsic asthma might present with an intolerance to monosodium glutamate if high doses are consumed.
/HUMAN EXPOSURE STUDIES/ Monosodium glutamate is widely regarded as the provocative agent in the "Chinese restaurant syndrome," of which flushing is regarded as part of the reaction. Six subjects were monitored by laser Doppler velocimetry for changes in facial cutaneous blood flow during challenge with monosodium glutamate and its cyclization product, pyroglutamate. Additionally, records of patients challenged with monosodium glutamate in the laboratory were reviewed. No flushing was provoked among the twenty four people tested, eighteen of whom gave a positive history of Chinese restaurant syndrome flushing. These results indicate that monosodium glutamate provoked flushing, if it exists at all, must be rare. Monosodium glutamate and its cyclization product, pyroglutamate, may provoke edema and associated symptoms.
Glutamate is absorbed from the gut by an active transport system specific for amino acids. This process is saturable, can be competitively inhibited, and is dependent on sodium ion concentration... . During intestinal absorption, a large proportion of glutamic acid is transaminated and consequently alanine levels in portal blood are elevated. If large amounts of glutamate are ingested, portal glutamate levels increase ... . This elevation results in increased hepatic metabolism of glutamate, leading to release of glucose, lactate, glutamine, and other amino acids, into systemic circulation ... . The pharmacokinetics of glutamate depend on whether it is free or incorporated into protein, and on the presence of other food components. Digestion of protein in the intestinal lumen and at the brush border produces a mixture of small peptides and amino acids; di-and tri-peptides may enter the absorptive cells where intracellular hydrolysis may occur, liberating further amino acids. Defects are known in both amino acid and peptide transport ... .. Glutamic acid in dietary protein, together with endogenous protein secreted into the gut, is digested to free amino acids and small peptides, both of which are absorbed into mucosal cells where peptides are hydrolyzed to free amino acids and some of the glutamate is metabolized. Excess glutamate and other amino acids appear in portal blood. As a consequence of the rapid metabolism of glutamate in intestinal mucosal cells and in the liver, systemic plasma levels are low, even after ingestion of large amounts of dietary protein. /Glutamic acid/
... Intestinal and hepatic metabolism results in elevation of levels in systemic circulation only after extremely high doses given by gavage (>30mg/kg body weight). Ingestion of monosodium glutamate (MSG) was not associated with elevated levels in maternal milk, and glutamate did not readily pass the placental barrier. Human infants metabolized glutamate similarly to adults.
Oral administration of pharmacologically high doses of glutamate results in elevated plasma levels. The peak plasma glutamate levels are both dose and concentration dependent ... . When the same dose (1 g/kg b.w.) of monosodium glutamate (MSG) was administered by gavage in aqueous solution to neonatal rats, increasing the concentration from 2% to 10% caused a five-fold increase in the plasma area under curve; similar results were observed in mice ... . Conversely, when MSG (1.5 g/kg b.w.) was administered to 43-day-old mice by gavage at varying concentrations of 2 to 20% w/v, no correlation could be established between plasma levels and concentration ...
Administration of a standard dose of 1 g/kg b.w. MSG by gavage as a 10% w/v solution resulted in a marked increase of plasma glutamate in all species studied. Peak plasma glutamate levels were lowest in adult monkeys (6 times fasting levels) and highest in mice (12-35 times fasting levels). Age-related differences between neonates and adults were observed; in mice and rats, peak plasma levels and area under curve were higher in infants than in adults while in guinea pigs the converse was observed.
