The essential amino acid lysine acts as precursor of glutamate in the mammalian central nervous system

Papes, Fábio; Surpili, Marcelo J.; Langone, Francesco; Trigo, José Roberto; Arruda, Paulo

doi:10.1016/s0014-5793(00)02401-7

Cited by 80 publications

(74 citation statements)

References 32 publications

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“…Consistent with initial neuronal injury, expression of Gcdh and the first enzyme in lysine degradation, lysineoxoglutarate reductase (29), are both limited to neurons. These data implicate the neuronal compartment as the predominant location of lysine catabolism and glutaric acid production in the brain.…”

Section: Discussionmentioning

confidence: 87%

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Zinnanti¹,

Lazović²,

Housman³

et al. 2007

J. Clin. Invest.

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Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance ( 1 H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I.

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Section: Discussionmentioning

confidence: 87%

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Zinnanti¹,

Lazović²,

Housman³

et al. 2007

J. Clin. Invest.

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“…Indeed, in preliminary magnetic resonance spectroscopic determinations of glutamate levels in brains of P0 GLS1Ϫ/Ϫ pups, we found that there is an ϳ50% reduction in glutamate levels compared with WT brains, with no reduction in GABA levels (Galloway et al, 2005). The persistence of glutamatergic synaptic transmission in GLS1 null mutants can be accounted for by other glutamate-synthetic pathways that have long been known in neurons such as transamination of ␣-ketoglutarate with alanine, branched-chain amino acids, or lysine (Papes et al, 2001;Hertz, 2004;Sweatt et al, 2004;Yudkoff et al, 2005). Direct reuptake of glutamate into neurons (Chen et al, 2004;Waagepetersen et al, 2005) could also account for relatively normal glutamatergic synaptic function in the absence of GLS1.…”

Section: Discussionmentioning

confidence: 99%

Mice Lacking Brain/Kidney Phosphate-Activated Glutaminase Have Impaired Glutamatergic Synaptic Transmission, Altered Breathing, Disorganized Goal-Directed Behavior and Die Shortly after Birth

Masson¹,

Darmon²,

Conjard³

et al. 2006

J. Neurosci.

117

128

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Neurotransmitter glutamate has been thought to derive mainly from glutamine via the action of glutaminase type 1 (GLS1). To address the importance of this pathway in glutamatergic transmission, we knocked out GLS1 in mice. The insertion of a STOP cassette by homologous recombination produced a null allele that blocked transcription, encoded no immunoreactive protein, and abolished GLS1 enzymatic activity. Null mutants were slightly smaller, were deficient in goal-directed behavior, hypoventilated, and died in the first postnatal day. No gross or microscopic defects were detected in peripheral organs or in the CNS. In cultured neurons from the null mutants, miniature EPSC amplitude and duration were normal; however, the amplitude of evoked EPSCs decayed more rapidly with sustained 10 Hz stimulation, consistent with an observed reduction in depolarization-evoked glutamate release. Because of this activitydependent impairment in glutamatergic transmission, we surmised that respiratory networks, which require temporal summation of synaptic input, would be particularly affected. We found that the amplitude of inspirations was decreased in vivo, chemosensitivity to CO 2 was severely altered, and the frequency of pacemaker activity recorded in the respiratory generator in the pre-Bötzinger complex, a glutamatergic brainstem network that can be isolated in vitro, was increased. Our results show that although alternate pathways to GLS1 glutamate synthesis support baseline glutamatergic transmission, the GLS1 pathway is essential for maintaining the function of active synapses, and thus the mutation is associated with impaired respiratory function, abnormal goal-directed behavior, and neonatal demise.

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“…Lysine, which is severely restricted in cereals, the most important staple food in the world. A reduced supply of lysine in the diet may lead to mental and physical handicaps because it is an important precursor for the novo synthesis of glutamate, the most significant neurotransmitter in the mammalian central nervous system [22] (Papes et al, 2001). The essential amino acids requirement for adult man weighing 70 kg is about 5.59 g per day [23].…”

Section: Amino Acid Compositionmentioning

confidence: 99%

“…Factors that affect the quality of flavor that processing of fish into the fish hydrolyzate using a combination of Biduri protease and papain. Amino acids found in many fish hydrolyzate is glutamic acid that had important roles as flavorenhancing compounds roomates provide an umami (savory) taste in food [22]. Specific flavor of fis ketchup and fish sauce are also determined by the type of spices used and the addition of brown sugar, so that the composition of different spices will give a different flavor as well.…”

Section: American Journal Of Food Science and Technologymentioning

confidence: 99%

Characteristics and Sensory Analysis of Ketchup and Sauce Products from "Bibisan" Fish Hydrolyzate

Witono¹,

Windrati²,

Taruna³

et al. 2014

AJFST

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"Bibisan" fish can be developed into a food flavor using enzymatic hydrolysis. The combination of "Biduri" protease and papain can shorten the time of hydrolysis. Bibisan fish hydrolyzate can be made derived products like the fish sauce and fish ketchup. Proximate analysis of fish sauce and ketchup observedincluding moisture content (72-74%), protein (9-10%), fat (9.15 to 16.3%), and ash (5.81 to 9.90%). Theabsorbance average value of Maillarddegree obtained from experiment then result of inferior fish sauce ranged from 0.432 to 0.463 while the fish ketchup ranged from 0228 to 0.281. Fish sauce color is lighter (light brown) instead of fish ketchup. Viscosity of fish sauce (14.86 to 18.78 mp) were also higher than fish ketchup (10.81 -14.80 mp). The highest amino acid inof bibisan fish hydrolyzate was glutamic acid that range from 8.76% -10.17%; while the lowest AA was histidine (1.12 to 1.22%). The sensory evaluation of fish sauce and ketchup reveals that the products have a good sensory quality and overall acceptability.

show abstract

The essential amino acid lysine acts as precursor of glutamate in the mammalian central nervous system

Cited by 80 publications

References 32 publications

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Mice Lacking Brain/Kidney Phosphate-Activated Glutaminase Have Impaired Glutamatergic Synaptic Transmission, Altered Breathing, Disorganized Goal-Directed Behavior and Die Shortly after Birth

Characteristics and Sensory Analysis of Ketchup and Sauce Products from "Bibisan" Fish Hydrolyzate

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