Glial Metabolism of Valine

Murín, Radovan; Mohammadi, Ghasem; Leibfritz, Dieter; Hamprecht, Bernd

doi:10.1007/s11064-008-9895-2

Cited by 29 publications

(26 citation statements)

References 39 publications

(92 reference statements)

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“…Specifically, oxidative BCAA degradation leads to Krebs cycle intermediates. 51, 52 Thus, alterations in energy metabolism upon paroxetine treatment could, at least in part, be influenced by altered BCAA concentrations. Furthermore, alterations in Krebs cycle intermediates were shown to result in altered neurotransmitter synthesis, 53 suggesting that increased BCAA levels could also influence synaptic transmission.…”

Section: Discussionmentioning

confidence: 99%

Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation

et al. 2011

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Currently used antidepressants elevate monoamine levels in the synaptic cleft. There is good reason to assume that this is not the only source for antidepressant therapeutic activities and that secondary downstream effects may be relevant for alleviating symptoms of depression. We attempted to elucidate affected biochemical pathways downstream of monoamine reuptake inhibition by interrogating metabolomic profiles in DBA/2Ola mice after chronic paroxetine treatment. Metabolomic changes were investigated using gas chromatography-mass spectrometry profiling and group differences were analyzed by univariate and multivariate statistics. Pathways affected by antidepressant treatment were related to energy metabolism, amino acid metabolism and hormone signaling. The identified pathways reveal further antidepressant therapeutic action and represent targets for drug development efforts. A comparison of the central nervous system with blood plasma metabolite alterations identified GABA, galactose-6-phosphate and leucine as biomarker candidates for assessment of antidepressant treatment effects in the periphery.

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Section: Discussionmentioning

confidence: 99%

Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation

et al. 2011

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“…Amino acids such as leucine, isoleucine and valine can be broken down in glial cultures to metabolites that can enter the tricarboxlic acid cycle directly or even produce lactate itself [35-37]. …”

Section: Introductionmentioning

confidence: 99%

Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism - effects of medication

Oades

Dauvermann

Schimmelmann

et al. 2010

Behavioral and Brain Functions

120

118

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BackgroundChildren with attention-deficit/hyperactivity disorder (ADHD) show a marked temporal variability in their display of symptoms and neuropsychological performance. This could be explained in terms of an impaired glial supply of energy to support neuronal activity.MethodWe pursued one test of the idea with measures of a neurotrophin reflecting glial integrity (S100B) and the influences of 8 cytokines on the metabolism of amino-acids, and of tryptophan/kynurenine to neuroprotective or potentially toxic products that could modulate glial function. Serum samples from 21 medication-naïve children with ADHD, 21 typically-developing controls, 14 medicated children with ADHD and 7 healthy siblings were analysed in this preliminary exploration of group differences and associations.ResultsThere were no marked group differences in levels of S100B, no major imbalance in the ratios of pro- to anti-inflammatory interleukins nor in the metabolism of kynurenine to toxic metabolites in ADHD. However, four trends are described that may be worthy of closer examination in a more extensive study. First, S100B levels tended to be lower in ADHD children that did not show oppositional/conduct problems. Second, in medicated children raised interleukin levels showed a trend to normalisation. Third, while across all children the sensitivity to allergy reflected increased levels of IL-16 and IL-10, the latter showed a significant inverse relationship to measures of S100B in the ADHD group. Fourthly, against expectations healthy controls tended to show higher levels of toxic 3-hydroxykynurenine (3 HK) than those with ADHD.ConclusionsThus, there were no clear signs (S100B) that the glial functions were compromised in ADHD. However, other markers of glial function require examination. Nonetheless there is preliminary evidence that a minor imbalance of the immunological system was improved on medication. Finally, if lower levels of the potentially toxic 3 HK in ADHD children were confirmed this could reflect a reduction of normal pruning processes in the brain that would be consistent with delayed maturation (supported here by associations with amino-acid metabolism) and a reduced metabolic source of energy.

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“…Generation and release of glutamine is not an event specific for aspartate. Rather, it is a frequently observed phenomenon of astrocytic metabolism of amino acids, as has been shown also for the metabolism of glycine [37] and the three branched-chain amino acids [3,23,24]. Also in the case of glutamine-and in that of alanine-a function as a fuel molecule for the energization of adjacent neurons has to be envisaged (for reviews see refs.…”

Section: Discussionmentioning

confidence: 98%

“…Thus they would release into the extracellular space the aspartate-derived metabolites lactate, glutamine, citrate, and alanine, thereby making them available to their neighboring cells, especially neurons. Consequently, as a feature of neuron-glia interaction, lactate generated in astrocytes from aspartate and many other molecular sources such as glucose [28], glycogen [16], glutamine [32], glycine [37], and branched-chain amino acids [3,23,24] would be forwarded to neurons as an oxidizable standard fuel material for energization. Generation and release of glutamine is not an event specific for aspartate.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of [U-13C]Aspartate by Astroglial Cultures: Nuclear Magnetic Resonance Analysis of the Culture Media

et al. 2010

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In brain the amino acid L-aspartate serves roles as: (1) putative transmitter, (2) protein precursor, (3) donor of atoms for the biosynthesis of pyrimidine and purine bases, and (4) fuel for energy metabolism. Astrocytes dominate aspartate clearance in brain, and in culture they take up aspartate and quickly metabolize it. In brain, only astrocytes were shown to express the enzymes for de novo pyrimidine biosynthesis. To gain more details about the spectrum of metabolites generated from aspartate and subsequently released by cultured astrocytes a (13)C-nuclear magnetic resonance analysis was performed of [U-(13)C]aspartate supplemented incubation media exposed to astroglial cultures. The results show that astrocytes readily metabolize aspartate and release into their culture media (13)C-isotopomers of lactate, glutamine, citrate and alanine. Despite the presence in astroglial cells of two tandem enzymes of pyrimidine biosynthesis and their mRNAs, pyrimidine nucleotide-related heterocyclic compounds such as dihydroorotate and orotate could not be detected in the culture media.

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Glial Metabolism of Valine

Cited by 29 publications

References 39 publications

Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation

Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation

Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism - effects of medication

Metabolism of [U-13C]Aspartate by Astroglial Cultures: Nuclear Magnetic Resonance Analysis of the Culture Media

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