Identity of D-3-aminoisobutyrate-pyruvate aminotransferase with alanine-glyoxylate aminotransferase 2

Kontani, Yasuhide; Kaneko, Masae; Kikugawa, Mariko; Fujimoto, Shigeyoshi; Tamaki, Nanaya

doi:10.1016/0304-4165(93)90131-q

Cited by 29 publications

(26 citation statements)

References 30 publications

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“…It seems possible that this antibody did not recognize the human enzyme. This aminotransferase has several activities, including D-3-aminobutyrate:pyruvate aminotransferase, ␤-alanine:pyruvate aminotransferase, and dimethylarginine:pyruvate aminotransferase activities, as well as AGT activity (21,24). Wanders et al (36) previously reported that AGT activity was apparent in the mitochondria of HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…GO, glycolate oxidase; GR, glyoxylate reductase; LDH, lactate dehydrogenase; AGT, alanine:glyoxylate aminotransferase; ␤-AlaAT, ␤-alaninepyruvate aminotransferase; GDH, glutamate dehydrogenase; N.D., not detected; N.M., not measured. mitochondria may be due to AGT2 activity, because these mitochondria contained ␤-AlaATII activity, a specific measure of AGT2 activity (21). This activity was enriched in mitochondria.…”

Section: Comparison Of Enzyme Activities In Hepg2 Cells and Human Livermentioning

confidence: 98%

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Glycolate and glyoxylate metabolism in HepG2 cells

Baker

Cramer

Kennedy

et al. 2004

American Journal of Physiology-Cell Physiology

104

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alate synthesis in human hepatocytes is not well defined despite the clinical significance of its overproduction in diseases such as the primary hyperoxalurias. To further define these steps, the metabolism to oxalate of the oxalate precursors glycolate and glyoxylate and the possible pathways involved were examined in HepG2 cells. These cells were found to contain oxalate, glyoxylate, and glycolate as intracellular metabolites and to excrete oxalate and glycolate into the medium. Glycolate was taken up more effectively by cells than glyoxylate, but glyoxylate was more efficiently converted to oxalate. Oxalate was formed from exogenous glycolate only when cells were exposed to high concentrations. Peroxisomes in HepG2 cells, in contrast to those in human hepatocytes, were not involved in glycolate metabolism. Incubations with purified lactate dehydrogenase suggested that this enzyme was responsible for the metabolism of glycolate to oxalate in HepG2 cells. The formation of 14 C-labeled glycine from 14 C-labeled glycolate was observed only when cell membranes were permeabilized with Triton X-100. These results imply that peroxisome permeability to glycolate is restricted in these cells. Mitochondria, which produce glyoxylate from hydroxyproline metabolism, contained both alanine:glyoxylate aminotransferase (AGT)2 and glyoxylate reductase activities, which can convert glyoxylate to glycine and glycolate, respectively. Expression of AGT2 mRNA in HepG2 cells was confirmed by RT-PCR. These results indicate that HepG2 cells will be useful in clarifying the nonperoxisomal metabolism associated with oxalate synthesis in human hepatocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Comparison Of Enzyme Activities In Hepg2 Cells and Human Livermentioning

confidence: 98%

Glycolate and glyoxylate metabolism in HepG2 cells

Baker

Cramer

Kennedy

et al. 2004

American Journal of Physiology-Cell Physiology

104

View full text Add to dashboard Cite

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“…The existing set may be biased toward components of the elongation machinery, since those mutants are more likely to be tested for this phenotype. Some reports suggest that 6AU may inhibit enzymes involved in amino acid catabolism such as aminoisobutyrate-pyruvate aminotransferase, albeit at relatively high drug concentrations (25,44,45). Nevertheless, there is currently a good correlation between the inability to induce PUR5 and mutations that affect transcript elongation.…”

Section: Discussionmentioning

confidence: 99%

Saccharomyces cerevisiae Transcription Elongation Mutants Are Defective in PUR5 Induction in Response to Nucleotide Depletion

Shaw

Reines

2000

Molecular and Cellular Biology

124

163

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IMP dehydrogenase (IMPDH) is the rate-limiting enzyme in the de novo synthesis of guanine nucleotides.It is a target of therapeutically useful drugs and is implicated in the regulation of cell growth rate. In the yeast Saccharomyces cerevisiae, mutations in components of the RNA polymerase II (Pol II) transcription elongation machinery confer increased sensitivity to a drug that inhibits IMPDH, 6-azauracil (6AU), by a mechanism that is poorly understood. This phenotype is thought to reflect the need for an optimally functioning transcription machinery under conditions of lowered intracellular GTP levels. Here we show that in response to the application of IMPDH inhibitors such as 6AU, wild-type yeast strains induce transcription of PUR5, one of four genes encoding IMPDH-related enzymes. Yeast elongation mutants sensitive to 6AU, such as those with a disrupted gene encoding elongation factor SII or those containing amino acid substitutions in Pol II subunits, are defective in PUR5 induction. The inability to fully induce PUR5 correlates with mutations that effect transcription elongation since 6AU-sensitive strains deleted for genes not related to transcription elongation are competent to induce PUR5. DNA encompassing the PUR5 promoter and 5 untranslated region supports 6AU induction of a luciferase reporter gene in wild-type cells. Thus, yeast sense and respond to nucleotide depletion via a mechanism of transcriptional induction that restores nucleotides to levels required for normal growth. An optimally functioning elongation machinery is critical for this response.

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“…1). The discovery of three potentially peroxisomal AGT2 homologs in plants is novel because animals contain a single AGT2 that catalyzes aminotransferase reactions with a wide range of substrates (Noguchi et al, 1978;Takada and Noguchi, 1980;Noguchi and Mori, 1981;Okuno et al, 1982;Ogawa et al, 1990;Kontani et al, 1993). The localization of AGT2 appears to be limited to mitochondria in animals, where its physiological role remains unclear (Takada and Noguchi, 1980;Noguchi and Mori, 1981;Ogawa et al, 1990;Lee et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Alanine Aminotransferase Homologs Catalyze the Glutamate:Glyoxylate Aminotransferase Reaction in Peroxisomes of Arabidopsis

2003

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Plant peroxisomal glyoxylate aminotransferases play central roles within the photorespiratory pathway. Genes encoding glyoxylate aminotransferases have been isolated from several animals and microbes, but only recently have plant homologs been identified. Three Arabidopsis homologs of alanine (Ala):glyoxylate aminotransferase 2 (AGT2) contain a putative type 1 peroxisomal targeting signal (PTS1), but the metabolic significance of these AGT2 homologs is unknown. GGT1 and GGT2 are Ala aminotransferase (AlaAT) homologs from Arabidopsis that represent another type of glyoxylate aminotransferase. These proteins are class I aminotransferases, each containing a putative PTS1. GGT1 and GGT2 are members of a small family of AlaATs in Arabidopsis. When expressed as recombinant proteins in Escherichia coli, GGT1 and GGT2 displayed biochemical characteristics very similar to one another, and to the Arabidopsis protein purified from leaves. Four aminotransferase activities were specifically associated with GGT1 and GGT2, using the substrate pairs glutamate (Glu):glyoxylate, Ala:glyoxylate, Glu:pyruvate, and Ala:2-oxoglutarate. GGT1 and GGT2 may have partially redundant functions; transcripts of both genes were detected in many of the same tissues. Although Glu:glyoxylate aminotransferase (GGT) activity has been observed in several locations in different plants and algae, including the cytoplasm and mitochondria, our subcellular fractionation data indicate that GGT activity was exclusively peroxisomal in Arabidopsis. Thus, glyoxylate aminotransferase reactions in plant peroxisomes appear to be catalyzed by at least two distinct types of aminotransferases: an AGT1 homolog with serine:glyoxylate aminotransferase activity Photorespiration is a metabolite salvage pathway coordinated among at least three organelles in plant cells: chloroplasts, peroxisomes, and mitochondria. In the process of recycling phosphoglycolate, generated by the oxygenase activity of Rubisco, into the photosynthetically useful metabolite phosphoglycerate, this pathway may consume a significant proportion of the energy generated by photosynthesis in C 3 plants (Ogren, 1984; Husic et al., 1987; Buchanan et al., 2000). Despite the obvious importance of photorespiration, genes encoding several enzymes of this pathway have not been identified.Leaf peroxisomes are hypothesized to contain at least four aminotransferase activities including Ser: glyoxylate aminotransferase (SGT), Glu:glyoxylate aminotransferase (GGT), Ala:glyoxylate aminotransferase (AGT), and Asp:2-oxoglutarate aminotransferase (AspAT; Rehfield and Tolbert, 1972). Studies in which isolated plant peroxisomes were fed labeled glycolate and various amino acids, in conjunction with studies of photorespiration mutants, have demonstrated that peroxisomal glyoxylate aminotransferases occupy central roles in photorespiration (Kisaki and Tolbert, 1969;Somerville and Ogren, 1980; Chang and Huang, 1981; Betsche, 1983;Liang and Huang, 1983;Yu et al., 1984).Although genes encoding glyoxylate aminotransferase...

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Identity of D-3-aminoisobutyrate-pyruvate aminotransferase with alanine-glyoxylate aminotransferase 2

Cited by 29 publications

References 30 publications

Glycolate and glyoxylate metabolism in HepG2 cells

Glycolate and glyoxylate metabolism in HepG2 cells

Saccharomyces cerevisiae Transcription Elongation Mutants Are Defective in PUR5 Induction in Response to Nucleotide Depletion

Alanine Aminotransferase Homologs Catalyze the Glutamate:Glyoxylate Aminotransferase Reaction in Peroxisomes of Arabidopsis

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