Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of glucagon on serine: pyruvate/alanine: glyoxylate aminotransferase (SPT/AGT) gene expression were studied in primary cultured rat hepatocytes. When hepatocytes had been precultured for 16-18 h under serum- and hormone-free conditions, the addition of glucagon caused (after a lag period of about 2 h) a remarkable increase in the cellular level of SPT/AGT mRNA by 4 h in a time- and dose-dependent manner. The induced mRNA was that for mitochondrial SPT/AGT, as judged by ribonuclease protection analysis. A nuclear run-on assay revealed that activation of transcription is responsible for the increase in mitochondrial SPT/AGT mRNA and that the maximal rate of transcription occurs 1.5 h after glucagon addition. The effect of glucagon was mimicked by 8-bromo-cAMP and suppressed by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, an inhibitor of cAMP-dependent protein kinase (protein kinase A), while both 12-O-tetradecanoylphorbol-13-acetate and A23187 were without effect in elevating the SPT/AGT mRNA level, suggesting that the cAMP/protein kinase A system is involved in the regulation of SPT/AGT gene expression. In hepatocytes precultured for 16-18 h under serum- and hormone-free conditions, the glucagon-induced transcription was severely inhibited by cycloheximide. When the preculture was for 2 h, on the other hand, the activation of transcription by glucagon was more rapid, and the inhibition by cycloheximide was less than that observed with cells precultured for 16-18 h, suggesting that a short-lived protein factor is involved in the hormonal regulation. The glucagon-induced expression of the SPT/AGT gene was also turned off by dexamethasone.
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PMID:Regulation by glucagon of serine: pyruvate/alanine: glyoxylate aminotransferase gene expression in cultured rat hepatocytes. 813 20

We have reported the isolation of genomic clones encoding serine:pyruvate aminotransferase (SPT; also named alanine:glyoxylate aminotransferase, AGT) (T. Oda, T. Funai, and A. Ichiyama, 1990, J. Biol. Chem. 265: 7513-7519). These clones contained the entire SPT/AGT gene of 10 kb. In this work, we characterized this gene. The SPT/AGT gene consists of 11 exons, and the exon-intron boundaries have typical splice donor and acceptor sequences. Determination of the nucleotide sequence up to -1.25 kb from the transcription initiation site revealed the presence of many putative cis elements, some of which may explain the transcriptional regulation of the SPT/AGT gene by glucagon and glucocorticoid. The nucleotide sequence around the 5' flanking region of the rat SPT/AGT gene and the whole gene organization were compared with those of the human SPT/AGT gene. No obvious similarities were observed in the 5' flanking region up to -1.25 kb from the initiation site of the gene, but exons 2 to 10 of the rat and human genes have identical sizes and show high similarities.
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PMID:Characterization and sequence analysis of rat serine:pyruvate/alanine:glyoxylate aminotransferase gene. 840 72

In rat liver, a single serine:pyruvate/alanine:glyoxylate aminotransferase (SPT or SPT/AGT) gene is transcribed from two transcription initiation sites. Transcription from the upstream site generates the mRNA encoding the precursor for mitochondrial SPT (pSPTm) and is markedly enhanced by the administration of glucagon or cAMP. In this report we show the increase in the downstream transcript, the peroxisomal SPT (SPTp) mRNA, caused by peroxisome proliferators and triiodothyronine (T3). In the case of T3, the pSPTm mRNA was also increased 72 h after a single administration of the hormone in addition to an earlier increase in SPTp mRNA.
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PMID:Induction by peroxisome proliferators and triiodothyronine of serine:pyruvate/alanine:glyoxylate aminotransferase of rat liver. 942 25

L-Serine metabolism in rat liver was investigated, focusing on the relative contributions of the three pathways, one initiated by L-serine dehydratase (SDH), another by serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), and the other involving serine hydroxymethyltransferase and the mitochondrial glycine cleavage enzyme system (GCS). Because serine hydroxymethyltransferase is responsible for the interconversion between serine and glycine, SDH, SPT/AGT, and GCS were considered to be the metabolic exits of the serine-glycine pool. In vitro, flux through SDH was predominant in both 24-h starved and glucagon-treated rats. Flux through SPT/AGT was enhanced by glucagon administration, but even after the induction, its contribution under quasi-physiological conditions (1 mM L-serine and 0.25 mM pyruvate) was about (1)/(10) of that through SDH. Flux through GCS accounted for only several percent of the amount of L-serine metabolized. Relative contributions of SDH and SPT/AGT to gluconeogenesis from L-serine were evaluated in vivo based on the principle that 3H at the 3 position of L-serine is mostly removed in the SDH pathway, whereas it is largely retained in the SPT/AGT pathway. The results showed that SPT/AGT contributed only 10-20% even after the enhancement of its activity by glucagon. These results suggested that SDH is the major metabolic exit of L-serine in rat liver.
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PMID:Flux of the L-serine metabolism in rat liver. The predominant contribution of serine dehydratase. 1034 51

Serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT) is largely located in mitochondria in carnivores, whereas it is entirely found within peroxisomes in herbivores and humans. In rat liver, SPT/AGT is found in both of these organelles, and only the mitochondrial enzyme is markedly induced by glucagon. Although SPT/AGT is a bifunctional enzyme involved in the metabolism of both L-serine and glyoxylate, its contribution to L-serine metabolism is independent of mitochondrial or peroxisomal localization (Xue HH et al., J Biol Chem 274: 16028-16033, 1999). Therefore, the species-specific and food habit-dependent organelle distribution might be required for proper metabolism of glyoxylate at the subcellular site of its formation. Glyoxylate formation from glycolate and that from L-hydroxyproline have been shown to occur in peroxisomes and mitochondria, respectively. The present study found that urinary excretion of oxalate was markedly increased when a large dose of L-hydroxyproline or glycolate was administered to rats. Oxalate formation from L-hydroxyproline but not that from glycolate was significantly reduced when mitochondrial SPT/AGT had been induced by glucagon. The hydroxyproline content of collagen is 10 to 13%, and collagen accounts for about 30% of total animal protein; therefore, these results suggest that an important role of mitochondrial SPT/AGT in carnivores is to convert L-hydroxyproline-derived glyoxylate into glycine in situ, preventing undesirable overflow into the production of oxalate.
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PMID:Control of oxalate formation from L-hydroxyproline in liver mitochondria. 1266 Mar 28

Serine:pyruvate (or alanine:glyoxylate) aminotransferase (SPT or AGT) in the liver is unique in that its subcellular distribution is entirely peroxisomal in man and herbivores, and largely mitochondrial in carnivores. In rats, this enzyme is located in both mitochondria and peroxisomes and only the mitochondrial activity is markedly induced by glucagon. The mechanism of the species-specific dual organelle localization is either transcription of the gene from two different start sites or loss of upstream translation initiation ATG codon by mutations. In herbivores, peroxisomal localization of SPT appears to be indispensable to prevent excessive oxalate production by removing glyoxylate, an immediate precursor of oxalate, formed from glycolate in this organelle. In carnivores, its mitochondrial localization appears to be needed to metabolize glyoxylate formed from L-hydroxyproline in mitochondria. In addition, SPT contributes substantially to gluconeogenesis from serine in rabbit, human and dog livers, irrespective of its mitochondrial or peroxisomal localization. (Communicated by Shigetada Nakanishi, M.J.A.).
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PMID:Studies on a unique organelle localization of a liver enzyme, serine:pyruvate (or alanine:glyoxylate) aminotransferase. 2155 62