Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For a number of organisms, the ability to withstand periods of nutrient deprivation correlates directly with lifespan. However, the underlying molecular mechanisms are poorly understood. We show that deletion of the N-myristoylprotein, Sip2p, reduces resistance to nutrient deprivation and shortens lifespan in Saccharomyces cerevisiae. This reduced lifespan is due to accelerated aging, as defined by loss of silencing from telomeres and mating loci, nucleolar fragmentation, and accumulation of extrachromosomal rDNA. Genetic studies indicate that sip2Delta produces its effect on aging by increasing the activity of Snf1p, a serine/threonine kinase involved in regulating global cellular responses to glucose starvation. Biochemical analyses reveal that as yeast age, hexokinase activity increases as does cellular ATP and NAD(+) content. The change in glucose metabolism represents a new correlate of aging in yeast and occurs to a greater degree, and at earlier generational ages in sip2Delta cells. Sip2p and Snf1p provide new molecular links between the regulation of cellular energy utilization and aging.
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PMID:Sip2p and its partner snf1p kinase affect aging in S. cerevisiae. 1092 2

We have identified many dark-inducible (din) genes that are expressed in Arabidopsis leaves kept in the dark. In the present study we addressed the question of how plant cells sense the depletion of sugars, and how sugar starvation triggers din gene expression in suspension-cultured cells of Arabidopsis. Depletion of sucrose in the medium triggered marked accumulation of din transcripts. Suppression of din gene expression by 2-deoxy-Glc, and a non-suppressive effect exerted by 3-O-methyl-Glc, suggested that sugar-repressible expression of din genes is mediated through the phosphorylation of hexose by hexokinase, as exemplified in the repression of photosynthetic genes by sugars. We have further shown that the signaling triggered by sugar starvation involves protein phosphorylation and dephosphorylation events, and have provided the first evidence that multiple pathways of protein dephosphorylation exist in sugar starvation-induced gene expression. An inhibitor of serine/threonine protein kinase, K-252a, inhibited din gene expression in sugar-depleted cells. Okadaic acid, which may preferentially inhibit type 2A protein phosphatases over type 1, enhanced the transcript levels of all din genes, except din6 and din10, under sugar starvation. Conversely, a more potent inhibitor of type 1 and 2A protein phosphatases, calyculin A, increased transcripts from din2 and din9, but decreased those from other din genes, in sugar-depleted cells. On the other hand, calyculin A, but not okadaic acid, completely inhibited the gene expression of chlorophyll a/b-binding protein under sugar starvation. These results indicate that multiple signaling pathways, mediated by different types of protein phosphatases, regulate gene expression during sugar starvation.
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PMID:Multiple signaling pathways in gene expression during sugar starvation. Pharmacological analysis of din gene expression in suspension-cultured cells of Arabidopsis. 1108 Feb 91

In plants, sugars are required to sustain growth and regulate gene expression. A large set of genes are either up- or down-regulated by sugars; however, whether there is a common mechanism and signal transduction pathway for differential and coordinated sugar regulation remain unclear. In the present study, the rice (Oryza sativa cv Tainan 5) cell culture was used as a model system to address this question. Sucrose and glucose both played dual functions in gene regulation as exemplified by the up-regulation of growth-related genes and down-regulation of stress-related genes. Sugar coordinately but differentially activated or repressed gene expression, and nuclear run-on transcription and mRNA half-life analyses revealed regulation of both the transcription rate and mRNA stability. Although coordinately regulated by sugars, these growth- and stress-related genes were up-regulated or down-regulated through hexokinase-dependent and/or hexokinase-independent pathways. We also found that the sugar signal transduction pathway may overlap the glycolytic pathway for gene repression. alpha-Amylase and the stress-related genes identified in this study were coordinately expressed under sugar starvation, suggesting a convergence of the nutritional and environmental stress signal transduction pathways. Together, our studies provide a new insight into the complex signal transduction network and mechanisms of sugar regulation of growth and stress-related genes in plants.
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PMID:Sugar coordinately and differentially regulates growth- and stress-related gene expression via a complex signal transduction network and multiple control mechanisms. 1116 Oct 45

Branched-chain alpha-keto acid dehydrogenase (BCKDH), a multienzyme complex, plays a key role in branched-chain amino acid catabolism. However, it remains unclear whether expression of each subunit is coordinately regulated in plants, which should be important for the efficient assembly of subunits into a functional multienzyme complex. We show that the transcripts from the Arabidopsis E1alpha subunit gene accumulated in dark-adapted leaves and in sugar-starved suspension cells. These results are complementary to our previous report that the transcripts for the E1beta and E2 subunit genes accumulated in sugar-starved cells. Expression of the E1alpha gene is likely to be regulated by hexokinase-mediated sugar signaling, indicating that sugar plays a regulatory role in the coordinated expression of BCKDH subunit genes. Furthermore, Leu and its metabolite alpha-ketoisocaproate have synergistic effects on the enhanced expression of BCKDH subunit genes under sugar starvation. We hence suggest that branched-chain amino acids activate their own degradation pathway in sugar-starved cells through co-induction of each subunit gene of BCKDH.
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PMID:Leucine and its keto acid enhance the coordinated expression of genes for branched-chain amino acid catabolism in Arabidopsis under sugar starvation. 1141 32

We have previously proposed that metabolic status is important in the regulation of cucumber malate synthase (MS) and isocitrate lyase (ICL) gene expression during plant development. In this article, we used a cell culture system to demonstrate that intracellular metabolic status does influence expression of both of these genes. Starvation of cucumber cell cultures resulted in the coordinate induction of the expression of MS and ICL genes, and this effect was reversed when sucrose was returned to the culture media. The induction of gene expression was closely correlated with a drop in intracellular sucrose, glucose, and fructose below threshold concentrations, but it was not correlated with a decrease in respiration rate. Glucose, fructose, or raffinose in the culture media also resulted in repression of MS and ICL. Both 2-deoxyglucose and mannose, which are phosphorylated by hexokinase but not further metabolized, specifically repressed MS and ICL gene expression relative to a third glyoxylate cycle gene, malate dehydrogenase. However, the addition of 3-methylglucose, an analog of glucose that is not phosphorylated, did not result in repression of either MS or ICL. It is proposed that the signal giving rise to a change in gene expression originates from the intracellular concentration of hexose sugars or the flux of hexose sugars into glycolysis.
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PMID:Carbon Catabolite Repression Regulates Glyoxylate Cycle Gene Expression in Cucumber. 1224 57

The roots of alternate-bearing citrus (Murcott, a Citrus reticulata hybrid) trees undergo extreme fluctuations of carbohydrate abundance and starvation. Using this system, we investigated the effect of root carbohydrate (total soluble sugar, sucrose and starch) depletion on carbohydrate-related gene expression. A series of genes, including those coding for starch phosphorylase ( STPH-L and STPH-H), ADP-glucose pyrophosphorylase, small subunit ( Agps), R1, plastidic ADP/ATP transporter ( AATP), phosphoglucomutase ( PGM-P and PGM-C), sucrose synthase ( CitSuS1 and CitSuSA), sucrose transporter ( SUT1 and SUT2), hexokinase ( HK) and alpha-amylase ( alpha-AMY), have been isolated and their expression analyzed. The genes were found to respond differentially to carbohydrate depletion. STPH-L, STPH-H, Agps, R1, AATP, PGM-P, PGM-C, CitSuS1 and HK were down-regulated while SUT1 and alpha-AMY were up-regulated during carbohydrate depletion. Two other genes, CitSuSA and SUT2, did not respond to carbohydrate depletion. Fruit removal, which interrupted the carbohydrate depletion induced by heavy fruiting, reversed these gene expression patterns. Trunk girdling and whole-plant darkening treatments, which brought about root carbohydrate depletion, induced the same changes in gene expression obtained in the alternate-bearing system. The possible roles of the up- and down-regulated genes in the metabolism of carbohydrate-depleted citrus roots are discussed. Although the specific signals involved have not been determined, the results support the feast/famine hypothesis of carbohydrate regulation proposed by Koch [K.E. Koch (1996) Annu Rev Plant Physiol Plant Mol Biol 47:509-540].
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PMID:Effects of carbohydrate starvation on gene expression in citrus root. 1272 44

A full-length coding domain sequence of a gene analogous to granule-bound starch synthase (GBSS; ADP-glucose-starch glucosyltransferase, EC 2.4.1.21) was cloned and defined as OsGBSSII based on a Nitrogen (N)-starvation-induced cDNA library constructed using the rapid subtraction hybridization method. The deduced amino acid sequence of OsGBSSII was 62-85% identical to those of GBSS proteins from other plant species. The exon/intron organization of OsGBSSII was similar to that of OsGBSSI. OsGBSSII was mainly expressed in leaves and its protein was exclusively bound to starch granules in rice leaves, which suggests that the amylose in rice leaves is synthesized by OsGBSSII. N-starvation-induced expression of OsGBSSII could be repressed by supplying nitrate, ammonia or amino acid (glutamic acid or glutamine), glucosamine (an inhibitor of hexokinase) or dark conditions. These results indicate that N-starvation induction was dependent on the photosynthetic product and hexokinase in rice leaves. Sugars induced the accumulation of OsGBSSII transcripts in excised leaves through glycolysis-dependent pathways. OsGBSSII gene expression is regulated by the circadian rhythm in rice leaves.
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PMID:Cloning and characterization of the granule-bound starch synthase II gene in rice: gene expression is regulated by the nitrogen level, sugar and circadian rhythm. 1295 12

In plants, excess cellular lysine (Lys) is catabolized into glutamic acid and acetyl-coenzyme A; yet, it is still not clear whether this pathway has other functions in addition to balancing Lys levels. To address this issue, we examined the effects of stress-related hormones, abscisic acid (ABA), and jasmonate, as well as various metabolic signals on the production of the mRNA and polypeptide of the bifunctional Lys-ketoglutarate reductase (LKR)/saccharopine dehydrogenase (SDH) enzyme, which contains the first two linked enzymes of Lys catabolism. The level of LKR/SDH was strongly enhanced by ABA, jasmonate, and sugar starvation, whereas excess sugars and nitrogen starvation reduced its level; thus this pathway appears to fulfill multiple functions in stress-related and carbon/nitrogen metabolism. Treatments with combination of hormones and/or metabolites, as well as use of ABA mutants in conjunction with the tester sugars mannose and 3-O-methyl-glucose further supported the idea that the hormonal and metabolic signals apparently operate through different signal transduction cascades. The stimulation of LKR/SDH protein expression by ABA is regulated by a signal transduction cascade that contains the ABI1-1 and ABI2-1 protein phosphatases. By contrast, the stimulation of LKR/SDH protein expression by sugar starvation is regulated by the hexokinase-signaling cascade in a similar manner to the repression of many photosynthetic genes by sugars. These findings suggest a metabolic and mechanistic link between Lys catabolism and photosynthesis-related metabolism in the regulation of carbon/nitrogen partitioning.
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PMID:Synthesis of the Arabidopsis bifunctional lysine-ketoglutarate reductase/saccharopine dehydrogenase enzyme of lysine catabolism is concertedly regulated by metabolic and stress-associated signals. 1457 81

There has been some debate whether leaf senescence is induced by sugar starvation or by sugar accumulation. External supply of sugars has been shown to induce symptoms of senescence such as leaf yellowing. However, it was so far not clear if sugars have a signalling function during developmental senescence. Glucose and fructose accumulate strongly during senescence in Arabidopsis thaliana (L.) Heynh. leaves. Using Affymetrix GeneChip analysis we determined the effect of sugar-induced senescence on gene expression. Growth on glucose in combination with low nitrogen supply induced leaf yellowing and changes in gene expression that are characteristic of developmental senescence. Most importantly, the senescence-specific gene SAG12, which was previously thought to be sugar-repressible, was induced over 900-fold by glucose. Induction of SAG12, which is expressed during late senescence, demonstrates that processes characteristic for late stages are sugar-inducible. Two MYB transcription factor genes, PAP1 and PAP2, were identified as senescence-associated genes that are induced by glucose. Moreover, growth on glucose induced genes for nitrogen remobilisation that are typically enhanced during developmental senescence, including the glutamine synthetase gene GLN1;4 and the nitrate transporter gene AtNRT2.5. In contrast to wild-type plants, the hexokinase-1 mutant gin2-1 did not accumulate hexoses and senescence was delayed. Induction of senescence by externally supplied glucose was partially abolished in gin2-1, indicating that delayed senescence was a consequence of decreased sugar sensitivity. Taken together, our results show that Arabidopsis leaf senescence is induced rather than repressed by sugars.
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PMID:Effect of sugar-induced senescence on gene expression and implications for the regulation of senescence in Arabidopsis. 1651 42

Cereal kernel growth and grain yield are functions of endosperm starch accumulation. The objective of this study was to examine how various metabolic factors in developing maize (Zea mays L.) endosperm influence starch deposition. Kernels were grown in vitro on medium with: (a) zero N (-N), (b) optimum N (+N), or (c) -N from 3 to 20 days after pollination followed by +N until maturity (+/-N) to produce different degrees of endosperm growth and to promote an enhancement of starch synthesis midway through development. At intervals, kernels were harvested and levels of enzyme activities and carbohydrate and N constituents examined. Endosperm starch and protein accumulation were decreased in -N compared to +N kernels, but relief of N starvation increased both constituents. With greater movement of N into +/-N kernels, endosperm sugar concentrations declined suggesting an inverse relationship between C and N transport. Unusually high concentrations of sugar in N stressed kernels did not appear to limit or enhance starch production. Rather, increased accumulation of starch in +/-N endosperm was correlated with significant increases in the enzymatic activities of sucrose synthase and PPi-linked phosphofructokinase, and to a lessor extent hexokinase. In addition, the occurrence of specific proteins of the albumin/globulin fraction either increased, decreased, or remained unchanged in relation to starch synthesis. These data suggest that lack of N limits starch deposition in maize endosperm primarily through an influence on synthesis of key proteins.
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PMID:Nitrogen-induced changes in the growth and metabolism of developing maize kernels grown in vitro. 1666 40


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