Alanine Aminotransferase in Bovine Brain: Purification and Properties

Ruscák, M; Orlický, J; Žúbor, Vladimír; Hager, Hermann

doi:10.1111/j.1471-4159.1982.tb04720.x

Cited by 38 publications

(4 citation statements)

References 37 publications

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“…The Ala-Pyr model (Figure 4a, blue shading and burgundy text and arrows) involves cytoplasmic and mitochondrial isoforms of alanine aminotransferase (Ruščák et al, 1982), Alt1 and Alt2, respectively, and pyruvate (MPC) and alanine (AlC) carriers, which are present in mitochondria and described in the review by Taylor (2017). This pathway has been shown to be of high importance when MPC function is disrupted and for Gln metabolism in cancer cells (Taylor, 2017).…”

Section: Discussionmentioning

confidence: 99%

Mechanistic stoichiometric relationship between the rates of neurotransmission and neuronal glucose oxidation: Reevaluation of and alternatives to the pseudo‐malate‐aspartate shuttle model

Rothman

Behar

Dienel

2022

Journal of Neurochemistry

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The ~1:1 stoichiometry between the rates of neuronal glucose oxidation (CMRglc‐ox–N) and glutamate (Glu)/γ‐aminobutyric acid (GABA)‐glutamine (Gln) neurotransmitter (NT) cycling between neurons and astrocytes (VNTcycle) has been firmly established. However, the mechanistic basis for this relationship is not fully understood, and this knowledge is critical for the interpretation of metabolic and brain imaging studies in normal and diseased brain. The pseudo‐malate‐aspartate shuttle (pseudo‐MAS) model established the requirement for glycolytic metabolism in cultured glutamatergic neurons to produce NADH that is shuttled into mitochondria to support conversion of extracellular Gln (i.e., astrocyte‐derived Gln in vivo) into vesicular neurotransmitter Glu. The evaluation of this model revealed that it could explain half of the 1:1 stoichiometry and it has limitations. Modifications of the pseudo‐MAS model were, therefore, devised to address major knowledge gaps, that is, submitochondrial glutaminase location, identities of mitochondrial carriers for Gln and other model components, alternative mechanisms to transaminate α‐ketoglutarate to form Glu and shuttle glutamine‐derived ammonia while maintaining mass balance. All modified models had a similar 0.5 to 1.0 predicted mechanistic stoichiometry between VNTcycle and the rate of glucose oxidation. Based on studies of brain β‐hydroxybutyrate oxidation, about half of CMRglc‐ox–N may be linked to glutamatergic neurotransmission and localized in pre‐synaptic structures that use pseudo‐MAS type mechanisms for Glu‐Gln cycling. In contrast, neuronal compartments that do not participate in transmitter cycling may use the MAS to sustain glucose oxidation. The evaluation of subcellular compartmentation of neuronal glucose metabolism in vivo is a critically important topic for future studies to understand glutamatergic and GABAergic neurotransmission.image

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Section: Discussionmentioning

confidence: 99%

Mechanistic stoichiometric relationship between the rates of neurotransmission and neuronal glucose oxidation: Reevaluation of and alternatives to the pseudo‐malate‐aspartate shuttle model

Rothman

Behar

Dienel

2022

Journal of Neurochemistry

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“…It is reasonable to speculate that the amino group from Glu is used for pyruvate amination produced from glycolytic pathway, thus preventing pH drop. Alanine aminotransferase (ALAT; EC 2.6.1.2) that catalyzes amino group transfer between Glu and pyruvate is found in primary neurons and brain tissue (McKenna et al 2000, Westergaard et al 1993, Ruščák et al 1982). However, the cytosolic pathway for FA synthesis requires malonyl-CoA production from acetyl-CoA which requires 1 mole of ATP per mole of malonyl-CoA.…”

Section: Discussionmentioning

confidence: 99%

Fatty acid biosynthesis from glutamate and glutamine is specifically induced in neuronal cells under hypoxia

Brose

Marquardt

Golovko

2013

Journal of Neurochemistry

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Hypoxia is involved in many neuronal and non-neuronal diseases, and defining the mechanisms for tissue adaptation to hypoxia is critical for the understanding and treatment of these diseases. One mechanism for tissue adaptation to hypoxia is increased glutamine and/or glutamate (Gln/Glu) utilization. To address this mechanism, we determined total Gln/Glu incorporation into lipids and fatty acids in both primary neurons and a neuronal cell line under normoxic and hypoxic conditions and compared this to non-neuronal primary cells and non-neuronal cell lines. Incorporation of Gln/Glu into total lipids was dramatically and specifically increased under hypoxia in neuronal cells including both primary (2.0- and 3.0- fold for Gln and Glu, respectively) and immortalized cultures (3.5- and 8.0- fold for Gln and Glu, respectively), and 90% to 97% of this increase was accounted for by incorporation into fatty acids (FA) depending upon substrate and cell type. All other non-neuronal cells tested demonstrated decreased or unchanged FA synthesis from Gln/Glu under hypoxia. Consistent with these data, total FA mass was also increased in neuronal cells under hypoxia that was mainly accounted for by the increase in saturated and monounsaturated FA with carbon length from 14 to 24. Incorporation of FA synthesized from Gln/Glu was increased in all major lipid classes including cholesteryl esters, TAGs, DAGs, free FA, and phospholipids, with the highest rate of incorporation into TAGs. These results indicate that increased FA biosynthesis from Gln/Glu followed by esterification may be a neuronal specific pathway for adaptation to hypoxia.

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“…There are three enzymes, ALT, AAT, and GLDH, which, in BM, convert alanine and glutamate to α -ketoglutarate ( α -KG) [94, 132]. The enzymes are found structurally colocalized and may form functional complexes without releasing the intermediary metabolites [68, 94].…”

Section: Activation Of Oxidative Phosphorylation During Simultanementioning

confidence: 99%

“…The three glutamate-transforming enzymes have high Michaelis constants for glutamate: for GLDH 8–17 mM [142] and for ALT and AST in the range of 7–20 mM [132]. However, in view of the electrogenic nature of the aralar and removal of α -KG by the TCA cycle [45], in energized BM, the three glutamate-transforming reactions operate irreversibly with the net loss of glutamate.…”

Section: Activation Of Oxidative Phosphorylation During Simultanementioning

confidence: 99%

Fatty Acids in Energy Metabolism of the Central Nervous System

Panov

Orynbayeva

Вавилин

et al. 2014

BioMed Research International

150

144

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In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain's energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups.

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Alanine Aminotransferase in Bovine Brain: Purification and Properties

Cited by 38 publications

References 37 publications

Mechanistic stoichiometric relationship between the rates of neurotransmission and neuronal glucose oxidation: Reevaluation of and alternatives to the pseudo‐malate‐aspartate shuttle model

Mechanistic stoichiometric relationship between the rates of neurotransmission and neuronal glucose oxidation: Reevaluation of and alternatives to the pseudo‐malate‐aspartate shuttle model

Fatty acid biosynthesis from glutamate and glutamine is specifically induced in neuronal cells under hypoxia

Fatty Acids in Energy Metabolism of the Central Nervous System

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