Hydrogen Exchange at the β‐Carbon of Amino Acids during Transamination

Walter, Ulrich; Luthe, Hilmar; Söling, Hans‐Dieter; Gerhart, F.

doi:10.1111/j.1432-1033.1975.tb02467.x

Cited by 31 publications

(13 citation statements)

References 15 publications

(3 reference statements)

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“…To assess in situ ALT activity, we quantified the 2 H enrichment of hepatic alanine hydrogen atoms from 2 H-labelled water. Both the C3 methyl and C2 methine hydrogen atoms become enriched from 2 H 2 O via the ALT-mediated exchange of alanine and pyruvate, and enrichment of the methyl hydrogen atoms is abolished by AOA ( 41 ) . This exchange was demonstrated for catfish in situ by the rapid equilibration of tissue alanine and bulk water 2 H enrichment following placement in a tank enriched with 4 % 2 H 2 O ( 42 ) .…”

Section: Discussionmentioning

confidence: 99%

Effects of alanine aminotransferase inhibition on the intermediary metabolism inSparus auratathrough dietary amino-oxyacetate supplementation

et al. 2011

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In liver, through the reaction catalysed by alanine aminotransferase (ALT), alanine becomes an effective precursor for gluconeogenesis. In the present study amino-oxyacetate (AOA) was used to evaluate its effect on liver ALT activity of the carnivorous fish Sparus aurata. Moreover, the derived metabolic effects on metabolites and other key enzymes of glycolysis, gluconeogenesis and the pentose phosphate pathway were also studied. A dose-effect-dependent inhibition of AOA on hepatic cytosolic and mitochondrial ALT activity was observed in vitro. In vivo, AOA behaved as an inhibitor of hepatic cytosolic ALT activity. A long-term exposure to AOA increased pyruvate kinase activity in the liver irrespective of the composition of the diet supplied to fish. 1 H NMR studies showed that inclusion of AOA to the diet decreased the hepatic levels of alanine, glutamate and glycogen. Moreover, 2 H NMR analysis indicated a higher renewal rate for alanine in the liver of fish fed with a high-carbohydrate/low-protein diet, while AOA decreased alanine 2 H-enrichment irrespective of the diet. The present study indicates that AOA-dependent inhibition of the cytosolic ALT activity could help to increase the use of dietary carbohydrate nutrients.

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Section: Discussionmentioning

confidence: 99%

Effects of alanine aminotransferase inhibition on the intermediary metabolism inSparus auratathrough dietary amino-oxyacetate supplementation

et al. 2011

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“…It is important to recognize that the mechanism of aminotransferase-catalyzed H/ 2 H exchange with solvent described above allows H ϩ (or tritium) release from C-3 of amino acid substrates as a direct result of enzyme activity (36). However, once tritium is released by this process, it would not be restored to the substrate by reversal of the AAT reaction or by action of another enzyme because of 3 H dilution in the massive H ϩ pool represented by aqueous solvent.…”

Section: Discussionmentioning

confidence: 99%

Aspartate aminotransferase isotope exchange reactions: implications for glutamate/glutamine shuttle hypothesis

Kimmich

Roussie

Randles

2002

American Journal of Physiology-Cell Physiology

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Aspartate aminotransferase (AAT) catalyzes amino group transfer from glutamate (Glu) or aspartate (Asp) to a keto acid acceptor-oxaloacetate (OA) or alpha-ketoglutarate (KG), respectively. Data presented here show that AAT catalyzes two partial reactions resulting in isotope exchange between 3H-labeled Glu or 3H-labeled Asp and the cognate keto acid in the absence of the keto acid acceptor required for the net reaction. Tritiated keto acid product was detected by release of 3H2O from C-3 during base-induced enolization. Tritium released directly from C-2 (or C-3) by the enzyme was also evaluated and is a small fraction of that released because of exchange to the keto acid pool. Exchange is dependent on AAT concentration, time-dependent, proportional to the amino-to-keto acid ratio, and blocked by aminooxyacetate (AOA), an AAT inhibitor. Enzymatic conversion of [3H]KG to Glu by glutamic dehydrogenase (GDH) or of [3H]OA to malate by malic dehydrogenase (MDH) "protects" the label from release by base, showing that base-induced isotope release is from keto acid rather than a result of release during the exchange process. AAT isotope exchange is discussed in the context of the glutamate/glutamine shuttle hypothesis for astrocyte/neuron carbon cycling.

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“…On the other hand, analysis of lipogenic acetyl-CoA enrichment via N-acetyl p-amino benzoic acid (N-acetyl-PABA) in feeding mice revealed enrichments that were equivalent to that of body water [13]. Interestingly, GC-MS analyses of fatty acid enrichment from 2 H 2 O also indicate enrichment levels that are substantially below theoretical values [14][15][16] [17] hence the enrichment of acetyl-CoA derived from pyruvate is expected to approach that of body water. Acetyl-CoA derived via -oxidation will theoretically have two hydrogens out of three derived from body water, that is, a theoretical enrichment that is 67% of body water.…”

Section: Isotopic Studies Of Dnl and Acetyl-coa Enrichmentmentioning

confidence: 99%

Identifying Sources of Hepatic Lipogenic Acetyl-CoA Using Stable Isotope Tracers and NMR

Jones

2014

Advances in Radiology

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The role of hepaticde novolipogenesis (DNL) in promoting fatty liver disease and hypertriglyceridemia during excessive nutrient intake is becoming firmly established. Certain nutrients such as fructose promote hepatic DNL activity and this has been at least partly attributed to their efficient conversion to the acetyl-CoA precursors of DNL. However, tracer studies indicate a paradoxically low level of fructose incorporation into lipids, which begs the question of what the actual lipogenic acetyl-CoA sources are under these and other conditions. Here, we describe novel approaches for measuring substrate contributions to lipogenic hepatic acetyl-CoA using13C-tracers and13C-NMR analysis of lipids and acetyl-CoA probes. We review and address aspects of hepatic intermediary fluxes and acetyl-CoA compartmentation that can confound the relationship between13C-precursor substrate and lipogenic13C-acetyl-CoA enrichments and demonstrate novel methodologies that can provide realistic estimates of13C-enriched substrate contributions to DNL. The most striking realization is that the principal substrate contributors to lipogenic acetyl-CoA have yet to be identified, but they are probably not the so-called “lipogenic substrates” such as fructose. The proposed methods may improve our insight into the nutrient sources of DNL under various feeding and disease states.

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Hydrogen Exchange at the β‐Carbon of Amino Acids during Transamination

Abstract: The hydrogen exchange at the /?-carbon of L-alanine, L-glutamate and L-aspartate with water has been examined during transamination catalyzed by glutamic-oxdloacetic transaminase and by glu- Abbreviation. NMR, nuclear magnetic resonance. Enzymes.

Cited by 31 publications

References 15 publications

Effects of alanine aminotransferase inhibition on the intermediary metabolism inSparus auratathrough dietary amino-oxyacetate supplementation

Effects of alanine aminotransferase inhibition on the intermediary metabolism inSparus auratathrough dietary amino-oxyacetate supplementation

Aspartate aminotransferase isotope exchange reactions: implications for glutamate/glutamine shuttle hypothesis

Identifying Sources of Hepatic Lipogenic Acetyl-CoA Using Stable Isotope Tracers and NMR

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