Effects of aminooxyacetate on the metabolism of isolated liver cells

Rognstad, Robert; Clark, Dallas G.

doi:10.1016/0003-9861(74)90348-8

Cited by 96 publications

(30 citation statements)

References 19 publications

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“…It was therefore conceivable that the opposite effects of alanine and pyruvate on glucose transport are mediated by the same reaction, the direction in which it takes place determining whether a stimulation or an inhibition occurs. We consequently decided to examine the role of aminotransferases in the action of pyruvate on glucose transport by using selective inhibitors of these enzymes, namely ,-cycloserine [35] and amino-oxyacetate [36]. As illustrated in Table 6, these inhibitors alone (i.e.…”

Section: Signals Involved In Glucose Transport Inhibitionmentioning

confidence: 99%

Glucose transport and glucose transporter GLUT4 are regulated by product(s) of intermediary metabolism in cardiomyocytes

Fischer

Böttcher

Eblenkamp

et al. 1997

Biochemical Journal

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Alternative substrates of energy metabolism are thought to contribute to the impairment of heart and muscle glucose utilization in insulin-resistant states. We have investigated the acute effects of substrates in isolated rat cardiomyocytes. Exposure to lactate, pyruvate, propionate, acetate, palmitate, β-hydroxybutyrate or α-oxoglutarate led to the depression of glucose transport by up to 50 %, with lactate, pyruvate and propionate being the most potent agents. The percentage inhibition was greater in cardiomyocytes in which glucose transport was stimulated with the α-adrenergic agonist phenylephrine or with a submaximal insulin concentration than in basal or fully insulin-stimulated cells. Cardiomyocytes from fasted or diabetic rats displayed a similar sensitivity to substrates as did cells from control animals. On the other hand, the amination product of pyruvate (alanine), as well as valine and the aminotransferase inhibitors cycloserine and amino-oxyacetate, stimulated glucose transport about 2-fold. In addition, the effect of pyruvate was counteracted by cycloserine. Since reversible transamination reactions are known to affect the pool size of the citrate cycle, the influence of substrates, amino acids and aminotransferase

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Section: Signals Involved In Glucose Transport Inhibitionmentioning

confidence: 99%

Glucose transport and glucose transporter GLUT4 are regulated by product(s) of intermediary metabolism in cardiomyocytes

Fischer

Böttcher

Eblenkamp

et al. 1997

Biochemical Journal

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“…Briefly, livers from 18-h fasted rats (180 -220 g) were perfused (7) with nonrecirculating bicarbonate buffer (40 ml/min) containing the following: (i) 40% enriched NaH 13 CO 3 and 5 mM lactate, or 2 mM pyruvate Ϯ 0.3 mM MPA, or 0.5 mM AOA (protocol I), or (ii) dimethyl [1,4-13 C 2 ]succinate Ϯ 0.3 mM MPA (protocol II). In orientation experiments, we found that the labeling of gluconeogenic and CAC intermediates as well as glucose production were two to four times greater with dimethyl [1,[4][5][6][7][8][9][10][11][12][13] C 2 ]succinate than with [1,4-13 C 2 ]succinate (not shown). Similar ratios in glucose production from dimethyl succinate and succinate were reported by Rognstad (8).…”

Section: Methodsmentioning

confidence: 90%

“…The second substrate was dimethyl [1,4-13 C 2 ]succinate that labels PEP via reactions of the citric acid cycle and PEPCK. We modulated the rates of GNG from lactate, pyruvate, or [1,[4][5][6][7][8][9][10][11][12][13] C 2 ]succinate using mercaptopicolinate (MPA), an inhibitor of PEPCK (2, 3), or aminooxyacetate (AOA), an inhibitor of the glutamate-aspartate shuttle (4 -6). Our data reveal major incompatibilities in the labeling of gluconeogenic intermediates extracted from the whole rat liver.…”

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confidence: 99%

Metabolomic and Mass Isotopomer Analysis of Liver Gluconeogenesis and Citric Acid Cycle

Yang

Kasumov

Kombu

et al. 2008

Journal of Biological Chemistry

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In this second of two companion articles, we compare the mass isotopomer distribution of metabolites of liver gluconeogenesis and citric acid cycle labeled from NaH 13 CO 3 or dimethyl [1,4-13 C 2 ]succinate. The mass isotopomer distribution of intermediates reveals the reversibility of the isocitrate dehydrogenase ؉ aconitase reactions, even in the absence of a source of ␣-ketoglutarate. In addition, in many cases, a number of labeling incompatibilities were found as follows: (i) glucose versus triose phosphates and phosphoenolpyruvate; (ii) differences in the labeling ratios C-4/C-3 of glucose versus (glyceraldehyde 3-phosphate)/(dihydroxyacetone phosphate); and (iii) labeling of citric acid cycle intermediates in tissue versus effluent perfusate. Overall, our data show that gluconeogenic and citric acid cycle intermediates cannot be considered as sets of homogeneously labeled pools. This probably results from the zonation of hepatic metabolism and, in some cases, from differences in the labeling pattern of mitochondrial versus extramitochondrial metabolites. Our data have implications for the use of labeling patterns for the calculation of metabolic rates or fractional syntheses in liver, as well as for modeling liver intermediary metabolism.This second of two companion articles concentrates on a comparison of the mass isotopomer distributions of metabolites of gluconeogenesis and the citric acid cycle in livers perfused with precursors of [1-13 C]PEP. 2 One substrate was NaH 13 CO 3 that labels liver GNG from lactate or pyruvate via carboxylation and isotopic exchange reactions (1). The second substrate was dimethyl [1,4-13 C 2 ]succinate that labels PEP via reactions of the citric acid cycle and PEPCK. We modulated the rates of GNG from lactate, pyruvate, or [1,[4][5][6][7][8][9][10][11][12][13] C 2 ]succinate using mercaptopicolinate (MPA), an inhibitor of PEPCK (2, 3), or aminooxyacetate (AOA), an inhibitor of the glutamate-aspartate shuttle (4 -6). Our data reveal major incompatibilities in the labeling of gluconeogenic intermediates extracted from the whole rat liver. EXPERIMENTAL PROCEDURESMaterials-The materials and rat liver perfusion experiments are described in detail in the accompanying article (28). Briefly, livers from 18-h fasted rats (180 -220 g) were perfused (7) with nonrecirculating bicarbonate buffer (40 ml/min) containing the following: (i) 40% enriched NaH 13 CO 3 and 5 mM lactate, or 2 mM pyruvate Ϯ 0.3 mM MPA, or 0.5 mM AOA (protocol I), or (ii) dimethyl [1,4-13 C 2 ]succinate Ϯ 0.3 mM MPA (protocol II). In orientation experiments, we found that the labeling of gluconeogenic and CAC intermediates as well as glucose production were two to four times greater with dimethyl [1,4-13 C 2 ]succinate than with [1,4-13 C 2 ]succinate (not shown). Similar ratios in glucose production from dimethyl succinate and succinate were reported by Rognstad (8). Therefore, we conducted all the experiments of this group with 0.5 mM dimethyl [1,4-13 C 2 ]succinate Ϯ 0.3 mM MPA. Sample Preparation-Powdered fr...

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“…This compound is a potent inhibitor of pyridoxal phosphate requiring transaminases (23). Light-grown aplastidic cells were extracted in 50 mm phosphate and 5 mm EDTA, adjusted to pH 6.80 with NaOH, and passed through Sephadex G-25.…”

Section: Resultsmentioning

confidence: 99%

δ-Aminolevulinic Acid Formation from γ,δ-Dioxovaleric Acid in Extracts of Euglena gracilis

Foley¹,

Beale²

1982

Plant Physiol.

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y,-Dioxovaleric acid (DOVA) has been proposed as a precursor to heme and chlorophyll in plants aad algae but serves instead to supply non-plastid tetrapyrrole precursors when the plastids are metabolically quiescent (9).In plants, the major route to ALA formation utilizes the intact carbon skeleton of glutamate or a-ketoglutarate (5). This 5-carbon pathway has been shown to operate in the tissues of higher plants and in greening alga (2), including members of the Cyanophycae, Rhodophycae, Chlorophycae, and Euglena (24). Although the 5-carbon pathway has not yet been fully elucidated, it is considered to be responsible for providing precursors to Chl.Two biochemical routes from glutamate or a-ketoglutarate to ALA have been proposed. One involves the intermediate formation of glutamate-l-semialdehyde, and the other, the intermediate formation of DOVA. Enzyme activity capable of transaminating DOVA to ALA has been detected in mammalian tissues, nonphotosynthetic and photosynthetic bacteria, higher plant tissues, and greening algae, including Chlorella (10) and Euglena (25).Noguchi and Mori (18) have copurified DOVA:L-alanine aminotransferase and glyoxylate:L-alanine aminotransferase from bovine liver mitochondria, and they concluded that both activities are catalyzed by a single enzyme which exhibits much higher activity toward glyoxylate. Because of the structural similarity of DOVA and glyoxylate, it is likely that DOVA is accepted only as an artificial substrate and that DOVA transamination is of no physiological significance.We report here the purification and some properties of DOVA:L-glutamate aminotransferase from wild-type and aplastidic strains of E. gracilis, and its probable identity with glyoxylate:L-glutamate aminotransferase.

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Effects of aminooxyacetate on the metabolism of isolated liver cells

Cited by 96 publications

References 19 publications

Glucose transport and glucose transporter GLUT4 are regulated by product(s) of intermediary metabolism in cardiomyocytes

Glucose transport and glucose transporter GLUT4 are regulated by product(s) of intermediary metabolism in cardiomyocytes

Metabolomic and Mass Isotopomer Analysis of Liver Gluconeogenesis and Citric Acid Cycle

δ-Aminolevulinic Acid Formation from γ,δ-Dioxovaleric Acid in Extracts of Euglena gracilis

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