The Brain Barrier System—i the Exchange of Free Amino Acids Between Plasma and Brain

Lajtha, Ábel; Mela, Paula

doi:10.1111/j.1471-4159.1961.tb13505.x

Cited by 70 publications

(3 citation statements)

References 6 publications

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“…Irrespective of the mechanism by which methionine levels are reduced, decreased methionine availability would be expected to reduce its brain levels. In support of this, it has been demonstrated that the administration of intravenous amino acids results in an increase in their levels in the brain (Lajtha and Mela, 1961 ).…”

Section: Discussionmentioning

confidence: 87%

Traumatic Brain Injury Alters Methionine Metabolism: Implications for Pathophysiology

Dash

Hergenroeder

Jeter³

et al. 2016

Front. Syst. Neurosci.

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Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM) that serves as the principal methyl (−CH3) donor for DNA and histone methyltransferases (MTs) to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling. Under conditions of oxidative stress, homocysteine (which is derived from SAM) enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI) alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (HV; n = 20) and patients with mild TBI (mTBI; GCS > 12; n = 20) or severe TBI (sTBI; GCS < 8; n = 20) within the first 24 h of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS). sTBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to HV, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline). mTBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser degrees than detected in the sTBI group. Taken together, these results suggest that decreased levels of methionine and its metabolic products are likely to alter cellular function in multiple organs at a systems level.

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Section: Discussionmentioning

confidence: 87%

Traumatic Brain Injury Alters Methionine Metabolism: Implications for Pathophysiology

Dash

Hergenroeder

Jeter³

et al. 2016

Front. Syst. Neurosci.

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“…There appear to be precise homeostatic mechanisms which tend to maintain the constancy of the free amino acid levels despite changes in the rate of protein turnover. LAJTHA and MELA (1961) suggested that alterations in influx or efflux rates may be of great importance in the regulation of the free amino acid pool. In most studies on picrotoxin and pentylenetetrazol, however, the duration of action of the drug and the duration of the seizure were very brief.…”

Section: Richter Andmentioning

confidence: 99%

Free Amino Acids and Related Compounds in Dog Brain: Post‐mortem and Anoxic Changes, Effects of Ammonium Chloride Infusion, and Levels During Seizures Induced by Picrotoxin and by Pentylenetetrazol*

Tews

Carter

Roa

et al. 1963

Journal of Neurochemistry

162

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“…Consequently the possibility that the brain might take up 5-hydroxytryptophan assumes some importance. Uptake by the brain has been shown for other amino-acids: glutamic acid (Stem, Eggleston, Hems & Krebs, 1949), arginine and histidine (Neame, 1961a, b), leucine and lysine (Lajtha & Mela, 1961), methionine, ornithine and proline (Neame, 1961a), phenylalanine and tryptophan (Guroff & Udenfriend, 1962) and tyrosine (Chirigos, Greengard & Udenfriend, 1960;Guroff, King & Udenfriend, 1961). Entry of 5-hydroxytryptophan into the brain can occur in vivo, for its administration to animals increases brain concentrations of 5-hydroxytryptamine (Udenfriend, Weissbach & Bogdanski, 1957).…”

mentioning

confidence: 99%

UPTAKE OF 5‐HYDROXY[¹⁴C]TRYPTOPHAN BY RAT AND DOG BRAIN SLICES

Smith

1963

British Journal of Pharmacology and Chemotherapy

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Slices of rat brain take up and concentrate 5-hydroxy ['4C]tryptophan when incubated at 37°C in vitro. Uptake is inhibited by methyldopa and L-phenylalanine in a competitive manner. Only a small proportion of the 5-hydroxy["4C]tryptophan taken up is decarboxylated. This observation, and the lack of correlation between the effects of various amino-acid inhibitors on uptake and on decarboxylase, suggest that the two processes are not linked. In the cold some passive diffusion of the amino-acid occurs, as is thought to take place also at 370 C. Experiments with dog brain show that uptake varies from one part of the brain to another, being greatest in the caudate nucleus. The possible implications of the uptake mechanism in the treatment of animals or patients with large doses of amino-acids are discussed.

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The Brain Barrier System—i the Exchange of Free Amino Acids Between Plasma and Brain

Cited by 70 publications

References 6 publications

Traumatic Brain Injury Alters Methionine Metabolism: Implications for Pathophysiology

Traumatic Brain Injury Alters Methionine Metabolism: Implications for Pathophysiology

Free Amino Acids and Related Compounds in Dog Brain: Post‐mortem and Anoxic Changes, Effects of Ammonium Chloride Infusion, and Levels During Seizures Induced by Picrotoxin and by Pentylenetetrazol*

UPTAKE OF 5‐HYDROXY[¹⁴C]TRYPTOPHAN BY RAT AND DOG BRAIN SLICES

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The Brain Barrier System—i the Exchange of Free Amino Acids Between Plasma and Brain

Cited by 70 publications

References 6 publications

Traumatic Brain Injury Alters Methionine Metabolism: Implications for Pathophysiology

Traumatic Brain Injury Alters Methionine Metabolism: Implications for Pathophysiology

Free Amino Acids and Related Compounds in Dog Brain: Post‐mortem and Anoxic Changes, Effects of Ammonium Chloride Infusion, and Levels During Seizures Induced by Picrotoxin and by Pentylenetetrazol*

UPTAKE OF 5‐HYDROXY[14C]TRYPTOPHAN BY RAT AND DOG BRAIN SLICES

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UPTAKE OF 5‐HYDROXY[¹⁴C]TRYPTOPHAN BY RAT AND DOG BRAIN SLICES