Neurochemical effects ofl-pyroglutamic acid

Mello, Carlos Fernando; Vega, D.; Pizutti, Leandro Timm; Lopes, F P; Rubin, Maribel Antonello; Homerich, J G; Melo, Carlos R.; Somer, J. E.; Souza, Diogo Onofre Gomes de; Wajner, Moaçir

doi:10.1007/bf00970591

Cited by 4 publications

(6 citation statements)

References 21 publications

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“…While the transport rate of l ‐glutamate into cytoplasm was the highest among amino acids for P. oshimae , it was strongly inhibited by the presence of l ‐aspartate. In nerve cells, PGA inhibits l ‐glutamate transport by competitively binding at the l ‐glutamate receptor [3,5]. These evidences suggest a possible failure in efficient proton transport in thermoacidophiles by the presence of PGA as a structural analog of l ‐glutamate.…”

Section: Resultsmentioning

confidence: 93%

“…l ‐Pyroglutamic acid (2‐pyrrolidone‐5‐carboxylic acid, PGA) forms spontaneously from l ‐glutamate by the cyclization of internal amide, and its conversion rate is highly dependent on the temperature and pH of the l ‐glutamate solution [1]. Since its identification, the ‘forgotten’ amino acid has been reported to possess a strong neurotoxic effect on brain cell by reducing l ‐glutamate‐binding on neuron [2–5]. Competitive interaction between PGA and l ‐glutamate with glutamate receptors was ascribed to their structural similarity [3,5].…”

Section: Introductionmentioning

confidence: 99%

“…Since its identification, the ‘forgotten’ amino acid has been reported to possess a strong neurotoxic effect on brain cell by reducing l ‐glutamate‐binding on neuron [2–5]. Competitive interaction between PGA and l ‐glutamate with glutamate receptors was ascribed to their structural similarity [3,5]. In contrast to mammalian cells, little information is available on the effect of PGA on microorganisms to date.…”

Section: Introductionmentioning

confidence: 99%

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Inhibitory effect of l-pyroglutamate on extremophiles: correlation with growth temperature and pH

Park

Ryu

Lee

2003

FEMS Microbiology Letters

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L-Pyroglutamate (PGA) is naturally occurring from L-glutamate solution with accelerated formation rate under high temperature and low pH. Even though PGA has been identified as a neurotoxic agent on brain cells, the effect of PGA on the growth of microorganisms is rarely known. Here various kinds of microorganisms differing in their optimal growth temperature, pH, phylogeny, and isolated biotope were investigated for the effect of PGA. We found that growth of thermoacidophiles, including both archaea and bacteria, was seriously inhibited by the presence of PGA, and the extent of the inhibitory effect was closely related with growth temperature and pH. Interestingly, only microbes that grow at high temperature and low pH are inhibited by PGA, while this compound may stimulate growth rates of organisms that live at neutral pH and low temperature.

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibitory effect of l-pyroglutamate on extremophiles: correlation with growth temperature and pH

Park

Ryu

Lee

2003

FEMS Microbiology Letters

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“…In this study, we showed that L-glutamate, one of the most abundant amino acids in yeast extract, can be spontaneously converted to PGA during cultivation of hyperthermophiles and that PGA significantly suppresses growth of S. solfataricus. Although thermal conversion of L-glutamate to PGA was originally described several decades ago (31) and the role of PGA as an agonist for the glutamate receptor has been investigated with nerve cells (6,19), there have been no previous reports concerning the effects of PGA on the growth of microorganisms.…”

Section: Discussionmentioning

confidence: 99%

l -Pyroglutamate Spontaneously Formed from l -Glutamate Inhibits Growth of the Hyperthermophilic Archaeon Sulfolobus solfataricus

Park

Lee

Ryu

2001

Appl Environ Microbiol

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Identification of physiological and environmental factors that limit efficient growth of hyperthermophiles is important for practical application of these organisms to the production of useful enzymes or metabolites. During fed-batch cultivation of Sulfolobus solfataricus in medium containing L-glutamate, we observed formation of L-pyroglutamic acid (PGA). PGA formed spontaneously from L-glutamate under culture conditions (78°C and pH 3.0), and the PGA formation rate was much higher at an acidic or alkaline pH than at neutral pH. It was also found that PGA is a potent inhibitor of S. solfataricus growth. The cell growth rate was reduced by one-half by the presence of 5.1 mM PGA, and no growth was observed in the presence of 15.5 mM PGA. On the other hand, the inhibitory effect of PGA on cell growth was alleviated by addition of L-glutamate or L-aspartate to the medium. PGA was also produced from the L-glutamate in yeast extract; the PGA content increased to 8.5% (wt/wt) after 80 h of incubation of a yeast extract solution at 78°C and pH 3.0. In medium supplemented with yeast extract, cell growth was optimal in the presence of 3.0 g of yeast extract per liter, and higher yeast extract concentrations resulted in reduced cell yields. The extents of cell growth inhibition at yeast extract concentrations above the optimal concentration were correlated with the PGA concentration in the culture broth. Although other structural analogues of L-glutamate, such as L-methionine sulfoxide, glutaric acid, succinic acid, and L-glutamic acid ␥-methyl ester, also inhibited the growth of S. solfataricus, the greatest cell growth inhibition was observed with PGA. We also observed that unlike other glutamate analogues, N-acetyl-L-glutamate enhanced the growth of S. solfataricus. This compound was stable under cell culture conditions, and replacement of L-glutamate with N-acetyl-L-glutamate in the medium resulted in increased cell density.Recently, hyperthermophiles have attracted the attention of many workers in the biotechnology research community because of the potential industrial applications of these organisms and because they may provide a better understanding of how cell components are stabilized when they are heated (1,13,18,28,29). Despite the biotechnological potential of hyperthermophiles, thus far the uses of these organisms have been limited because of the low cell yields when they are cultivated, which are attributed mainly to a lack of knowledge concerning the physiological characteristics and high-temperature cultivation techniques (5, 17). Therefore, identification of physiological and environmental factors that limit efficient growth of hyperthermophiles and development of strategies to obtain high cell densities under high-temperature conditions are particularly important for increasing the biomass yields of these microorganisms in environments different from their natural habitats.Sulfolobus solfataricus P2 is a hyperthermophilic archaeon which normally grows at 75 to 85°C and pH 2.0 to 4.0 (4, 7, 32). Since phy...

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“…Pyroglutamic acid (PGA) is the primary thermal degradation product of glutamine (Gln) by releasing ammonia, besides, it is also the thermal degradation product of glutamic acid (Glu) by releasing water (Figure ) . According to reports in the literature, PGA has adverse effect on the central nervous system of patients by facilitating recurrent seizures . Most analytical methods based on HPLC in the literature that deal with PGA, focus on its determination in samples like commercial liquid nutritional products , coffee , human stratum corneum , peptides , etc.…”

Section: Introductionmentioning

confidence: 99%

Direct and simultaneous determination of methionine sulfoxide and pyroglutamic acid impurities in Compound Amino Acid Injection‐18 AA by ion‐pair reversed‐phase HPLC

Qin

et al. 2018

Separation Science Plus

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A direct and simultaneous determination of methionine sulfoxide and pyroglutamic acid impurities in Compound Amino Acid Injection‐18 AA by ion‐pair reversed‐phase high‐performance liquid chromatography with ultraviolet detection is described. The separation of both impurities in Compound Amino Acid Injection‐18 AA was accomplished with gradient elution consisting of acetonitrile and 10 mM diammonium hydrogen phosphate buffer (containing 15 mM sodium 1‐heptanesulfonate and obtaining pH 2.3 by addition of phosphoric acid). The limits of detection (μg/mL, S/N = 3:1) and quantification (μg/mL, S/N = 10:1) of methionine sulfoxide and pyroglutamic acid were 0.02 and 0.08, and 0.06 and 0.19, respectively. The linearity was in the range of 0.08–200.20 μg/mL for methionine sulfoxide and 0.19–201.20 μg/mL for pyroglutamic acid. The relatively simple method proved accurate (recovery 99.68–102.98% for methionine sulfoxide, 98.10–102.00% for pyroglutamic acid, n = 9) and precise (repeatability RSD = 1.06% for methionine sulfoxide, RSD = 0.60% for pyroglutamic acid, n = 6) in its application to commercial Compound Amino Acid Injection‐18 AA.

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Neurochemical effects ofl-pyroglutamic acid

Cited by 4 publications

References 21 publications

Inhibitory effect of l-pyroglutamate on extremophiles: correlation with growth temperature and pH

Inhibitory effect of l-pyroglutamate on extremophiles: correlation with growth temperature and pH

l -Pyroglutamate Spontaneously Formed from l -Glutamate Inhibits Growth of the Hyperthermophilic Archaeon Sulfolobus solfataricus

Direct and simultaneous determination of methionine sulfoxide and pyroglutamic acid impurities in Compound Amino Acid Injection‐18 AA by ion‐pair reversed‐phase HPLC

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