Kegg Pathway: Glycolysis / Gluconeogenesis

KEGG ID: 00010

Reference Diagram

KEGG Diagram for Glycolysis / Gluconeogenesis

Rat

There are 42 IPI Records from this pathway found in Rattus norvegicus.

Location of Glycolysis / Gluconeogenesis proteins on Rat Genome

IPI Record Position
1: Adh1 2:235799457-235810972
2: Adh4 2:235951062-235991514
3: Adh7 2:235749346-235765064
4: Akr1a1 5:136920556-136937697
5: Aldh1a3 1:120847746-120881883
6: Aldh1a7 1:223833318-223875827
7: Aldh2 12:36081803-36116118
8: Aldh3a1 10:47365155-47374873
9: Aldh3a2 10:47403406-47421068
10: Aldh9a1 13:83017310-83034047
11: Aldoa 1:185970658-185975486
12: Aldob 5:66283166-66296182
13: Aldoc 10:64308826-64311160
14: Dlat 8:53989473-54014779
15: Eno1 5:167394131-167405515
16: Eno2 4:160890158-160899068
17: Eno3 10:57536978-57542311
18: Fbp1 17:7795933-7817894
19: Fbp2 17:7824298-7841664
20: G6pc 10:90393597-90403140
21: Galm 6:3024123-3078725
22: Gapdhs 1:85773751-85783791
23: Gck 14:86572518-86587740
24: Hk1 :-
25: Hk2 4:116925725-116975211
26: Hk3 17:15651953-15669109
27: Ldha 1:97403075-97412547
28: Ldhal6b :-
29: Ldhb 4:180061568-180079530
30: Ldhc 1:97418622-97435277
31: LOC246267 :-
32: Pdha2 2:238983104-238991788
33: Pdhb 15:18737449-18743395
34: Pfkl 20:11009349-11032513
35: Pfkm 7:136822203-136846040
36: Pgam1 :-
37: Pgam2 14:86466036-86468173
38: Pgk1 X:94324142-94340190
39: Pgm1 5:120595650-120655915
40: Pklr 2:181214402-181223512
41: Pkm2 8:63486490-63508245
42: Tpi1 4:160933442-160936871

Mouse

There are 42 IPI Records from this pathway found in Mus musculus.

Location of Glycolysis / Gluconeogenesis proteins on Mouse Genome

IPI Record Position
1: Acss1 2:150309552-150359686
2: Acss2 2:155209389-155277165
3: Acyp1 12:86161509-86169538
4: Acyp2 11:30405992-30549396
5: Adh1 3:138215032-138228085
6: Adh4 3:138352896-138368183
7: Adh5 3:138380551-138392886
8: Adh7 3:138159100-138168593
9: Aldh1a3 7:66269840-66306401
10: Aldh1b1 4:45820149-45825699
11: Aldh2 5:121828319-121854203
12: Aldh3a1 11:61024940-61034609
13: Aldh3a2 11:61039612-61083380
14: Aldh3b1 19:3913493-3929737
15: Aldh7a1 18:56651105-56698241
16: Aldh9a1 1:169186888-169204961
17: Aldoa 7:126586384-126590331
18: Aldob 4:49557095-49570583
19: Aldoc 11:78139163-78143976
20: Bpgm 6:34406514-34435768
21: Dlat 9:50386865-50412010
22: Dld 12:31917620-31937471
23: Eno1 4:149081055-149092675
24: Eno2 6:124725672-124735128
25: Eno3 11:70473399-70478708
26: Fbp1 13:62874376-62897859
27: Fbp2 13:62846507-62867988
28: G6pc :-
29: Galm 17:80035797-80093358
30: Gapdhs 7:30438540-30452441
31: Gck 11:5800826-5850084
32: Gpi1 7:33910087-33939000
33: Hk2 6:82690705-82740117
34: Hk3 13:55015608-55030956
35: Ldha 7:46713883-46723668
36: Ldhal6b :-
37: Ldhb 6:142447474-142465179
38: Ldhc 7:46729305-46746184
39: Pdha1 X:155466324-155482441
40: Pdha2 3:141147957-141149132
41: Pdhb 14:6956612-6964490
42: Pfkl 10:77390400-77412878
43: Pfkm 15:97936598-97960480
44: Pfkp 13:6579120-6647970
45: Pgam1 3:10996931-10997695
46: Pgam2 11:5701647-5703736
47: Pgk1 3:58190923-58192176
48: Pgk2 17:39670753-39672006
49: Pgm2 5:64372085-64407313
50: Pklr 3:89222069-89231560
51: Pkm2 9:59454614-59477381
52: Tpi1 6:124776334-124780031

Human

There are 42 IPI Records from this pathway found in Homo sapiens.

Location of Glycolysis / Gluconeogenesis proteins on Human Genome

IPI Record Position
1: ACSS1 20:24934868-24987616
2: ACSS2 20:32926502-32979426
3: ACYP2 2:54195914-54385777
4: ADH1A 4:100416547-100431165
5: ADH1B 4:100445157-100461579
6: ADH1C :-
7: ADH4 4:100263855-100284472
8: ADH5 4:100212327-100225399
9: ADH6 4:100342818-100359426
10: ADH7 4:100552441-100575548
11: ADHFE1 8:67507287-67543596
12: AKR1A1 1:45788802-45808308
13: ALDH1A3 15:99237580-99274349
14: ALDH1B1 9:38382661-38388658
15: ALDH2 12:110688729-110732165
16: ALDH3A1 17:19581895-19592338
17: ALDH3A2 17:19492431-19521496
18: ALDH3B1 11:67534366-67553317
19: ALDH3B2 11:67186210-67198753
20: ALDH7A1 5:125908348-125958839
21: ALDH9A1 1:163898077-163934724
22: ALDOA 16:29971973-29989235
23: ALDOB 9:103222681-103237926
24: ALDOC 17:23924261-23928078
25: BPGM 7:133982095-134015105
26: DLAT 11:111401381-111439798
27: DLD 7:107318847-107347645
28: ENO1 1:8843648-8978713
29: ENO2 12:6893875-6903120
30: ENO3 17:4795135-4801150
31: FBP1 9:96405244-96441686
32: FBP2 9:96360823-96395896
33: G6PC 17:38306341-38318912
34: G6PC2 2:169466047-169474750
35: GALM 2:38746559-38815414
36: GAPDH 12:6513872-6517780
37: GAPDHS 19:40716204-40728058
38: GCK 7:44150395-44195563
39: GPI 19:39547727-39583072
40: HK1 10:70699762-70831644
41: HK2 2:74913290-74973982
42: HK3 5:176240680-176259284
43: LDHA 11:18372683-18385969
44: LDHAL6A 11:18434007-18457723
45: LDHAL6B 15:57286314-57287997
46: LDHB 12:21679543-21702043
47: LDHC 11:18390429-18429366
48: PDHA1 X:19271968-19289724
49: PDHA2 4:96980266-96981645
50: PDHB 3:58388398-58394594
51: PFKL 21:44544358-44571681
52: PFKM 12:46785973-46826154
53: PFKP 10:3099712-3169762
54: PGAM1 12:92558729-92559493
55: PGAM2 7:44068855-44071709
56: PGAM4 X:77111027-77111791
57: PGK1 X:77246327-77271449
58: PGK2 6:49861606-49862859
59: PGM1 1:63831535-63898504
60: PGM3 6:83933025-83959701
61: PKLR 1:153526254-153537849
62: PKM2 15:70278424-70310738
63: TPI1 12:6846619-6850526

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Recent Literature

Differential expression proteomics of human colorectal cancer based on a syngeneic cellular model for the progression of adenoma to carcinoma.

//www.hubmed.org/fulltext.cgi?uids=19899082">Proteomics</a>. 2009 Nov 6;
Roth U, Razawi H, Hommer J, Engelmann K, Schwientek T, Müller S, Baldus SE, Patsos G, Corfield AP, Paraskeva C, Hanisch FG

This is the first differential expression proteomics study on a human syngeneic cellular in vitro progression model of the colorectal adenoma-to-carcinoma sequence, the anchorage-dependent non-tumorigenic adenoma derived cell line AA/C1 and the derived anchorage-independent and tumorigenic carcinoma cell line AA/C1/SB10C. The study is based on quantitative 2-DE, and is complemented by westernblot validation. Excluding redundancies due to proteolysis and post-translational modified isoforms, of over 2.000 protein spots 13 proteins were revealed as regulated with statistical variance being within the 95(th) confidence level and were identified by peptide mass fingerprinting in MALDI mass spectrometry. Progression-associated proteins belong to the functional complexes of anaerobic Glycolysis</span>/Gluconeogenesis, steroid biosynthesis, prostaglandin biosynthesis, the regulation and maintainance of the cytoskeleton, protein biosynthesis and degradation, the regulation of apoptosis or other functions. Partial, but significant overlap was revealed with previous proteomics and transcriptomics studies in colorectal carcinoma. Among up-regulated proteins we identified 3-HMG-CoA synthase (HMGCS), protein phosphatase 1 (PP1), prostaglandin E synthase 2 (PTGES2), villin 1, annexin A1 (ANXA1), triosephosphate isomerase (TPIS), phosphoserine aminotransferase 1 (PSAT1), fumarylacetoacetate hydrolase (FAA) and pyrroline-5-carboxylate reductase 1 (PYCR1), while glucose-regulated protein 78 (GRP78), cathepsin D, lamin A/C and quinolate phosphoribosyltransferase (QPRT) were down-regulated.

Loading-related regulation of gene expression in bone in the contexts of estrogen deficiency, lack of estrogen receptor alpha and disuse.

//www.hubmed.org/fulltext.cgi?uids=19857613">Bone</a>. 2009 Oct 24;
Zaman G, Saxon LK, Sunters A, Hilton H, Underhill P, Williams D, Price JS, Lanyon LE

Loading-related changes in gene expression in resident cells in the tibia of female mice in the contexts of normality (WT), estrogen deficiency (WT-OVX), absence of estrogen receptor alpha (ERalpha(-/-)) and disuse due to sciatic neurectomy (WT-SN) were established by microarray. Total RNA was extracted from loaded and contra-lateral non-loaded tibiae at selected time points after a single, short period of dynamic loading sufficient to engender an osteogenic response. There were marked changes in the expression of many genes according to context as well as in response to loading within those contexts. In WT mice at 3, 8, 12 and 24 h after loading the expression of 642, 341, 171 and 24 genes, respectively, were differentially regulated compared with contra-lateral bones which were not loaded. Only a few of the genes differentially regulated by loading in the tibiae of WT mice have recognized roles in bone metabolism or have been linked previously to osteogenesis (Opn, Sost, Esr1, Tgfb1, Lrp1, Ostn, Timp, Mmp, Ctgf, Postn and Irs1, BMP and DLX5). The canonical pathways showing the greatest loading-related regulation were those involving pyruvate metabolism, mitochondrial dysfunction, calcium-induced apoptosis, Glycolysis</span>/Gluconeogenesis, aryl hydrocarbon receptor and oxidative phosphorylation. In the tibiae from WT-OVX, ERalpha(-/-) and WT-SN mice, 440, 439 and 987 genes respectively were differentially regulated by context alone compared to WT. The early response to loading in tibiae of WT-OVX mice involved differential regulation compared to their contra-lateral non-loaded pair of fewer genes than in WT, more down-regulation than up-regulation and a later response. This was shared by WT-SN. In tibiae of ERalpha(-/-) mice, the number of genes differentially regulated by loading was markedly reduced at all time points. These data indicate that in resident bone cells, both basal and loading-related gene expression is substantially modified by context. Many of the genes differentially regulated by the earliest loading-related response were primarily involved in energy metabolism and were not specific to bone.

Differential expression profiling of the synaptosome proteome in a rat model of antipsychotic resistance.

//www.hubmed.org/fulltext.cgi?uids=19660441">Brain Res</a>. 2009 Oct 27; 1295: 170-8
Ji B, Zhang Z, Zhang M, Zhu H, Zhou K, Yang J, Li Y, Sun L, Feng G, Wang Y, He L, Wan C

This study used a comparative proteomics approach to identify the effects of the antipsychotic drugs, Chlorpromazine (CPZ), Clozapine (CLZ), and Quetiapine (QTP) on the synaptosomal protein of the cerebral cortex of Sprague-Dawley (SD) rats. The multivariate statistical test partial least squares-discriminant analysis (PLS-DA) was applied to build the models for screening out the variable important plot (VIP). The PLS-DA models were able to distinguish each drug treatment group and the control group; more importantly, the univariate differentially expressed protein spots were capable of being verified by the VIP of the models. The interrelationships among the identified proteins were analyzed using Pearson's correlation analysis and pathway analysis. Through the synaptosome proteome experiments, we established that the energy production of the mitochondrial function and 'Glycolysis</span>/Gluconeogenesis' were involved in the response to antipsychotic medications. Furthermore, the G protein-coupled signal transduction system was also inhibited by antipsychotic medications. The result of our study should contribute to the understanding of the effects of antipsychotic drugs on synaptic function.

Insufficient activity of MAPK pathway is a key monitor of Kidney-Yang Deficiency Syndrome.

//www.hubmed.org/fulltext.cgi?uids=19500008">J Altern Complement Med</a>. 2009 Jun; 15(6): 653-60
Ding WJ, Yan SL, Zeng YZ, Li WH, Duan A, Zheng TE, Liu M, Tan CE, Teng X, Wan J

OBJECTIVE: To explore the genetic characteristics and molecular regulator of Kidney-Yang Deficiency Syndrome (KDS). DESIGN: A typical KDS family was collected using a questionnaire of cold feeling and a 40-item scoring table of KDS based on Traditional Chinese Medicine (TCM), by single-blind method repeated annually over three years. Their transcriptomes were assayed by microarray and validated by RT-PCR and ELISA. Simultaneously, 10 healthy volunteers were recruited as controls and the same protocols were performed. RESULTS: This typical KDS family has 35 members, of whom 11 were evaluated as having severe KDS and 6 as having common KDS. Results of the cDNA microarray revealed that there were 420 genes/expressed sequence tags differentially expressed in KDS transcriptomes, indicating a global functional impairment in the mass-energy-information carrying network of KDS patients, involving energy metabolism, signal transduction, development, cell cycle, and immunity. Pathway analysis by gene set enrichment assay (GSEA) and other tools demonstrated that mitogenic activated protein kinase (MAPK) is among the most insufficiently activated pathways, while the oxidative phosphorylation and Glycolysis</span>/Gluconeogenesis pathways, the two main pathways relevant to ATP synthesis, were among the most excessively activated pathways in KDS patients. Results of RT-PCR and ELISA confirmed the status of insufficient activity of the MAPK pathway. CONCLUSION: KDS patients undergo overall attenuated functions in the mass-energy-information carrying network. The marked low level of energy output in KDS may be primarily attributed to the insufficient activity of the MAPK pathway, which may be a key monitor for the abnormal energy metabolism and other impaired activities in KDS.

Antipsychotic treatment alters protein expression associated with presynaptic function and nervous system development in rat frontal cortex.

//www.hubmed.org/fulltext.cgi?uids=19400588">J Proteome Res</a>. 2009 Jul; 8(7): 3284-97
Ma D, Chan MK, Lockstone HE, Pietsch SR, Jones DN, Cilia J, Hill MD, Robbins MJ, Benzel IM, Umrania Y, Guest PC, Levin Y, Maycox PR, Bahn S

Haloperidol and olanzapine are widely used antipsychotic drugs in the treatment of schizophrenia and other psychotic disorders. Despite extensive research efforts within the biopharmaceutical industry and academia, the exact molecular mechanisms of their action remain largely unknown. Since the response of patients to existing medications can be variable and often includes severe side effects, it is critical to increase our knowledge on their mechanism of action to guide clinical usage and new drug development. In this study, we have employed the label-free liquid chromatography tandem mass spectrometry (LC-MSE) to identify differentially expressed proteins in rat frontal cortex following subchronic treatment with haloperidol or olanzapine. Subcellular fractionation was performed to increased proteomic coverage and provided insight into the subcellular location involved in the mechanism of drug action. LC-MSE profiling identified 531 and 741 annotated proteins in fractions I (cytoplasmic-) and II (membrane enriched-) in two drug treatments. Fifty-nine of these proteins were altered significantly by haloperidol treatment, 74 by olanzapine and 21 were common to both treatments. Pathway analysis revealed that both drugs altered similar classes of proteins associated with cellular assembly/organization, nervous system development/function (particularly presynaptic function) and neurological disorders, which indicate a common mechanism of action. The top affected canonical signaling pathways differed between the two treatments. The haloperidol data set showed a stronger association with Huntington's disease signaling, while olanzapine treatment showed stronger effects on Glycolysis</span>/Gluconeogenesis. This could either relate to a difference in clinical efficacy or side effect profile of the two compounds. The results were consistent with the findings reported previously by targeted studies, demonstrating the validity of this approach. However, we have also identified many novel proteins which have not been found previously to be associated with these drugs. Further study of these proteins could provide new insights into the etiology of the disease or the mechanism of antipsychotic medications.

Analysis of expressed sequence tags from Chaetomium cupreum grown under conditions associated with mycoparasitism.

//www.hubmed.org/fulltext.cgi?uids=19215580">Lett Appl Microbiol</a>. 2009 Mar; 48(3): 275-80
Zhang HY, Yang Q, Wang G, Shang FD

AIMS: To elucidate the molecular mechanisms associated with mycoparasitism from Chaetomium cupreum, an effective biocontrol agent with ability against plant pathogenic fungi. METHODS AND RESULTS: One cDNA library was constructed from conditions predicted to resemble mycoparasitic process. A total of 1876 ESTs were generated and assembled into 1035 unigenes. BlastX search revealed that 585 unigenes had similarities with sequences available from public databases. Based on the ESTs abundance, MFS monosaccharide transporter was found as the gene expressed at the highest level. A KEGG analysis allowed mapping of 60 metabolic pathways well represented by the Glycolysis</span>/Gluconeogenesis, D-arginine and ornithine metabolism, and tryptophan metabolism. The genes related to mycoparasitism were detected. CONCLUSIONS: The results revealed that the cell walls of the fungal pathogen can simulate some aspects of the mycoparasitic interaction between C. cupreum and its targets. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report to study genes expression under conditions associated with the mycoparasitic process. The findings contribute to elucidate the molecular mechanisms involved in mycoparasitism and will help to advance our efforts in developing novel strategies for biocontrol of plant fungal diseases.

Cognitive performance and age-related changes in the hippocampal proteome.

//www.hubmed.org/fulltext.cgi?uids=19135133">Neuroscience</a>. 2009 Mar 3; 159(1): 183-95
Freeman WM, Vanguilder HD, Bennett C, Sonntag WE

Declining cognitive performance is associated with increasing age, even in the absence of overt pathological processes. We and others have reported that declining cognitive performance is associated with age-related changes in brain glucose utilization, long-term potentiation and paired-pulse facilitation, protein expression, neurotransmitter levels, and trophic factors. However, it is unclear whether these changes are causes or symptoms of the underlying alterations in dendritic and synaptic morphology that occur with age. In this study, we examined the hippocampal proteome for age- and cognition-associated changes in behaviorally stratified young and old rats, using two-dimensional in-gel electrophoresis and MS/MS. Comparison of old cognitively intact with old cognitively impaired animals revealed additional changes that would not have been detected otherwise. Interestingly, not all age-related changes in protein expression were associated with cognitive decline, and distinct differences in protein expression were found when comparing old cognitively intact with old cognitively impaired rats. A large number of protein changes with age were related to the Glycolysis</span>/Gluconeogenesis pathway. In total, the proteomic changes suggest that age-related alterations act synergistically with other perturbations to result in cognitive decline. This study also demonstrates the importance of examining behaviorally-defined animals in proteomic studies, as comparison of young to old animals regardless of behavioral performance would have failed to detect many cognitive impairment-specific protein expression changes evident when behavioral stratification data were used.

A large number of protein expression changes occur early in life and precede phenotype onset in a mouse model for huntington disease.

//www.hubmed.org/fulltext.cgi?uids=19043139">Mol Cell Proteomics</a>. 2009 Apr; 8(4): 720-34
Zabel C, Mao L, Woodman B, Rohe M, Wacker MA, Kläre Y, Koppelstätter A, Nebrich G, Klein O, Grams S, Strand A, Luthi-Carter R, Hartl D, Klose J, Bates GP

Huntington disease (HD) is fatal in humans within 15-20 years of symptomatic disease. Although late stage HD has been studied extensively, protein expression changes that occur at the early stages of disease and during disease progression have not been reported. In this study, we used a large two-dimensional gel/mass spectrometry-based proteomics approach to investigate HD-induced protein expression alterations and their kinetics at very early stages and during the course of disease. The murine HD model R6/2 was investigated at 2, 4, 6, 8, and 12 weeks of age, corresponding to absence of disease and early, intermediate, and late stage HD. Unexpectedly the most HD stage-specific protein changes (71-100%) as well as a drastic alteration (almost 6% of the proteome) in protein expression occurred already as early as 2 weeks of age. Early changes included mainly the up-regulation of proteins involved in Glycolysis</span>/Gluconeogenesis and the down-regulation of the actin cytoskeleton. This suggests a period of highly variable protein expression that precedes the onset of HD phenotypes. Although an up-regulation of Glycolysis</span>/Gluconeogenesis-related protein alterations remained dominant during HD progression, late stage alterations at 12 weeks showed an up-regulation of proteins involved in proteasomal function. The early changes in HD coincide with a peak in protein alteration during normal mouse development at 2 weeks of age that may be responsible for these massive changes. Protein and mRNA data sets showed a large overlap on the level of affected pathways but not single proteins/mRNAs. Our observations suggest that HD is characterized by a highly dynamic disease pathology not represented by linear protein concentration alterations over the course of disease.

A comparative metabolomic study of NHR-49 in Caenorhabditis elegans and PPAR-alpha in the mouse.

//www.hubmed.org/fulltext.cgi?uids=18435929">FEBS Lett</a>. 2008 May 28; 582(12): 1661-6
Atherton HJ, Jones OA, Malik S, Miska EA, Griffin JL

Proton Nuclear Magnetic Resonance spectroscopy and Gas Chromatography Mass Spectrometry based metabolomics has been used in conjunction with multivariate statistics to examine the metabolic changes in Caenorhabditis elegans following the deletion of nuclear hormone receptor-49 (nhr-49). Deletion of the receptor produced profound changes in fatty acid metabolism, in particular an increase in the ratio of unsaturated to saturated fatty acids, a decrease in the concentration of glucose and increases in lactate and alanine. Given the proposed functional similarity between nhr-49 and the mammalian peroxisome proliferator-activated receptors (PPARs) these changes were compared with the metabolome of the PPAR-alpha null mouse. The metabolomic approach demonstrated a number of similarities including the regulation of lipid synthesis, beta-oxidation of fatty acids and changes in Glycolysis</span>/Gluconeogenesis.

An integrated genetic, genomic and systems approach defines gene networks regulated by the interaction of light and carbon signaling pathways in Arabidopsis.

//www.hubmed.org/fulltext.cgi?uids=18387196">BMC Syst Biol</a>. 2008; 2: 31
Thum KE, Shin MJ, Gutiérrez RA, Mukherjee I, Katari MS, Nero D, Shasha D, Coruzzi GM

BACKGROUND: Light and carbon are two important interacting signals affecting plant growth and development. The mechanism(s) and/or genes involved in sensing and/or mediating the signaling pathways involving these interactions are unknown. This study integrates genetic, genomic and systems approaches to identify a genetically perturbed gene network that is regulated by the interaction of carbon and light signaling in Arabidopsis. RESULTS: Carbon and light insensitive (cli) mutants were isolated. Microarray data from cli186 is analyzed to identify the genes, biological processes and gene networks affected by the integration of light and carbon pathways. Analysis of this data reveals 966 genes regulated by light and/or carbon signaling in wild-type. In cli186, 216 of these light/carbon regulated genes are misregulated in response to light and/or carbon treatments where 78% are misregulated in response to light and carbon interactions. Analysis of the gene lists show that genes in the biological processes "energy" and "metabolism" are over-represented among the 966 genes regulated by carbon and/or light in wild-type, and the 216 misregulated genes in cli186. To understand connections among carbon and/or light regulated genes in wild-type and the misregulated genes in cli186, the microarray data is interpreted in the context of metabolic and regulatory networks. The network created from the 966 light/carbon regulated genes in wild-type, reveals that cli186 is affected in the light and/or carbon regulation of a network of 60 connected genes, including six transcription factors. One transcription factor, HAT22 appears to be a regulatory "hub" in the cli186 network as it shows regulatory connections linking a metabolic network of genes involved in "amino acid metabolism", "C-compound/carbohydrate metabolism" and "Glycolysis</span>/Gluconeogenesis". CONCLUSION: The global misregulation of gene networks controlled by light and carbon signaling in cli186 indicates that it represents one of the first Arabidopsis mutants isolated that is specifically disrupted in the integration of both carbon and light signals to control the regulation of metabolic, developmental and regulatory genes. The network analysis of misregulated genes suggests that CLI186 acts to integrate light and carbon signaling interactions and is a master regulator connecting the regulation of a host of downstream metabolic and regulatory processes.

Large-scale mRNA expression profiling in the common ice plant, Mesembryanthemum crystallinum, performing C3 photosynthesis and Crassulacean acid metabolism (CAM).

//www.hubmed.org/fulltext.cgi?uids=18319238">J Exp Bot</a>. 2008; 59(7): 1875-94
Cushman JC, Tillett RL, Wood JA, Branco JM, Schlauch KA

The common ice plant (Mesembryanthemum crystallinum L.) has emerged as a useful model for molecular genetic studies of Crassulacean acid metabolism (CAM) because CAM can be induced in this species by water deficit or salinity stress. Non-redundant sequence information from expressed sequence tag data was used to fabricate a custom oligonucleotide microarray to compare large-scale mRNA expression patterns in M. crystallinum plants conducting C(3) photosynthesis versus CAM. Samples were collected every 4 h over a 24 h time period at the start of the subjective second day from plants grown under constant light and temperature conditions in order to capture variation in mRNA expression due to salinity stress and circadian clock control. Of 8455 genes, a total of 2343 genes (approximately 28%) showed a significant change as judged by analysis of variance (ANOVA) in steady-state mRNA abundance at one or more time points over the 24 h period. Of these, 858 (10%) and 599 (7%) exhibited a greater than two-fold ratio (TFR) increase or decrease in mRNA abundance, respectively. Functional categorization of these TFR genes revealed that many genes encoding products that function in CAM-related C(4) acid carboxylation/decarboxylation, Glycolysis</span>/Gluconeogenesis, polysaccharide, polyol, and starch biosynthesis/degradation, protein degradation, transcriptional activation, signalling, stress response, and transport facilitation, and novel, unclassified proteins exhibited stress-induced increases in mRNA abundance. In contrast, salt stress resulted in a significant decrease in transcript abundance for genes encoding photosynthetic functions, protein synthesis, and cellular biogenesis functions. Many genes with CAM-related functions exhibited phase shifts in their putative circadian expression patterns following CAM induction. This report establishes an extensive catalogue of gene expression patterns for future investigations aimed at understanding the complex, transcriptional hierarchies that govern CAM-specific expression patterns. A novel graph-theoretic approach called 'Max Clique Builder' is introduced that identifies and organizes sets of coordinately regulated genes, such as those encoding subunits of the vacuolar H(+)-ATPase complex, into tighter functionally related clusters with more similar expression patterns compared with standard hierarchical clustering methods.

Glycerate 2-kinase of Thermotoga maritima and genomic reconstruction of related metabolic pathways.

//www.hubmed.org/fulltext.cgi?uids=18156253">J Bacteriol</a>. 2008 Mar; 190(5): 1773-82
Yang C, Rodionov DA, Rodionova IA, Li X, Osterman AL

Members of a novel glycerate-2-kinase (GK-II) family were tentatively identified in a broad range of species, including eukaryotes and archaea and many bacteria that lack a canonical enzyme of the GarK (GK-I) family. The recently reported three-dimensional structure of GK-II from Thermotoga maritima (TM1585; PDB code 2b8n) revealed a new fold distinct from other known kinase families. Here, we verified the enzymatic activity of TM1585, assessed its kinetic characteristics, and used directed mutagenesis to confirm the essential role of the two active-site residues Lys-47 and Arg-325. The main objective of this study was to apply comparative genomics for the reconstruction of metabolic pathways associated with GK-II in all bacteria and, in particular, in T. maritima. Comparative analyses of approximately 400 bacterial genomes revealed a remarkable variety of pathways that lead to GK-II-driven utilization of glycerate via a Glycolysis</span>/Gluconeogenesis route. In the case of T. maritima, a three-step serine degradation pathway was inferred based on the tentative identification of two additional enzymes, serine-pyruvate aminotransferase and hydroxypyruvate reductase (TM1400 and TM1401, respectively), that convert serine to glycerate via hydroxypyruvate. Both enzymatic activities were experimentally verified, and the entire pathway was validated by its in vitro reconstitution.

Significant and systematic expression differentiation in long-lived yeast strains.

//www.hubmed.org/fulltext.cgi?uids=17971858">PLoS One</a>. 2007; 2(10): e1095
Cheng C, Fabrizio P, Ge H, Wei M, Longo VD, Li LM

BACKGROUND: Recent studies suggest that the regulation of longevity may be partially conserved in many eukaryotes ranging from yeast to mammals. The three yeast mutants sch9Delta, ras2Delta, tor1Delta show extended chronological life span up to three folds. Our aim is to dissect the mechanisms that lead to the yeast life span extension. METHODOLOGY/PRINCIPAL FINDINGS: We obtain gene expression profiles of sch9Delta, ras2Delta, tor1Delta as well as that for a wild type at day 2.5 in SDC medium using Affymetrix Yeast2.0 arrays. To accurately estimate the expression differentiation between the wild type and the long-lived mutants, we use sub-array normalization followed by a variant of the median-polishing summarization. The results are validated by the probe sets of S. pombe on the same chips. To translate the differentiation into changes of biological activities, we make statistical inference by integrating the expression profiles with biological gene subsets defined by Gene Ontology, KEGG pathways, and cellular localization of proteins. Other than subset-versus-other comparisons, we also make local comparisons between two directly-related gene subsets such as cytosolic and mitochondrial ribosomes. Our consensus is obtained by cross-examination of these inferences. The significant and systematic differentiation in the three long-lived strains includes: lower transcriptional activities; down-regulation of TCA cycle and oxidative phosphorylation versus up-regulation of the KEGG pathway Glycolysis</span>/Gluconeogenesis; the overall reduction of mitochondrial activities. We also report some different expression patterns such as reduction of the activities relating to mitosis in ras2Delta. CONCLUSIONS/SIGNIFICANCE: The modification of energy pathways and modification of compartment activities such as down-regulation of mitochondrial ribosome proteins versus up-regulation of cytosolic ribosome proteins are directly associated with the life span extension in yeast. The results provide a new and systematic S. cerevisiae version of the free radical theory from the perspective of functional genomics.

An integrated analysis of genes and pathways exhibiting metabolic differences between estrogen receptor positive breast cancer cells.

//www.hubmed.org/fulltext.cgi?uids=17883861">BMC Cancer</a>. 2007; 7: 181
Mandal S, Davie JR

BACKGROUND: The sex hormone estrogen (E2) is pivotal to normal mammary gland growth and differentiation and in breast carcinogenesis. In this in silico study, we examined metabolic differences between ER(+)ve breast cancer cells during E2 deprivation. METHODS: Public repositories of SAGE and MA gene expression data generated from E2 deprived ER(+)ve breast cancer cell lines, MCF-7 and ZR75-1 were compared with normal breast tissue. We analyzed gene ontology (GO), enrichment, clustering, chromosome localization, and pathway profiles and performed multiple comparisons with cell lines and tumors with different ER status. RESULTS: In all GO terms, biological process (BP), molecular function (MF), and cellular component (CC), MCF-7 had higher gene utilization than ZR75-1. Various analyses showed a down-regulated immune function, an up-regulated protein (ZR75-1) and glucose metabolism (MCF-7). A greater percentage of 77 common genes localized to the q arm of all chromosomes, but in ZR75-1 chromosomes 11, 16, and 19 harbored more overexpressed genes. Despite differences in gene utilization (electron transport, proteasome, Glycolysis</span>/Gluconeogenesis) and expression (ribosome) in both cells, there was an overall similarity of ZR75-1 with ER(-)ve cell lines and ER(+)ve/ER(-)ve breast tumors. CONCLUSION: This study demonstrates integral metabolic differences may exist within the same cell subtype (luminal A) in representative ER(+)ve cell line models. Selectivity of gene and pathway usage for strategies such as energy requirement minimization, sugar utilization by ZR75-1 contrasted with MCF-7 cells, expressing genes whose protein products require ATP utilization. Such characteristics may impart aggressiveness to ZR75-1 and may be prognostic determinants of ER(+)ve breast tumors.

Comparative proteomes of Corynebacterium glutamicum grown on aromatic compounds revealed novel proteins involved in aromatic degradation and a clear link between aromatic catabolism and Gluconeogenesis via fructose-1,6-bisphosphatase.

//www.hubmed.org/fulltext.cgi?uids=17880007">Proteomics</a>. 2007 Oct; 7(20): 3775-87
Qi SW, Chaudhry MT, Zhang Y, Meng B, Huang Y, Zhao KX, Poetsch A, Jiang CY, Liu S, Liu SJ

The current study examined the aromatic degradation and central metabolism in Corynebacterium glutamicum by proteomic and molecular methods. Comparative analysis of proteomes from cells grown on gentisate and on glucose revealed that 30% of the proteins of which their abundance changed were involved in aromatic degradation and central carbon metabolism. Similar results were obtained from cells grown on benzoate, 4-cresol, phenol, and resorcinol. Results from these experiments revealed that (i) enzymes involved in degradation of benzoate, 4-cresol, gentisate, phenol, and resorcinol were specifically synthesized and (ii) that the abundance of enzymes involved in central carbon metabolism of Glycolysis</span>/Gluconeogenesis, pentose phosphate pathway, and TCA cycles were significantly changed on various aromatic compounds. Significantly, three novel proteins, NCgl0524, NCgl0525, and NCgl0527, were identified on 4-cresol. The genes encoding NCgl0525 and NCgl0527 were confirmed to be necessary for assimilation of 4-cresol with C. glutamicum. The abundance of fructose-1,6-bisphosphatase (Fbp) was universally increased on all the tested aromatic compounds. This Fbp gene was disrupted and the mutant WT(Deltafbp) lost the ability to grow on aromatic compounds. Genetic complementation by the Fbp gene restored this ability. We concluded that Gluconeogenesis is a necessary process for C. glutamicum growing on various aromatic compounds.

Genetic evidence for a link between Glycolysis</span> and DNA replication.

//www.hubmed.org/fulltext.cgi?uids=17505547">PLoS One</a>. 2007; 2(5): e447
Jannière L, Canceill D, Suski C, Kanga S, Dalmais B, Lestini R, Monnier AF, Chapuis J, Bolotin A, Titok M, Le Chatelier E, Ehrlich SD

BACKGROUND: A challenging goal in biology is to understand how the principal cellular functions are integrated so that cells achieve viability and optimal fitness in a wide range of nutritional conditions. METHODOLOGY/PRINCIPAL FINDINGS: We report here a tight link between Glycolysis</span> and DNA synthesis. The link, discovered during an analysis of suppressors of thermosensitive replication mutants in bacterium Bacillus subtilis, is very strong as some metabolic alterations fully restore viability to replication mutants in which a lethal arrest of DNA synthesis otherwise occurs at a high, restrictive, temperature. Full restoration of viability by such alterations was limited to cells with mutations in three elongation factors (the lagging strand DnaE polymerase, the primase and the helicase) out of a large set of thermosensitive mutants affected in most of the replication proteins. Restoration of viability resulted, at least in part, from maintenance of replication protein activity at high temperature. Physiological studies suggested that this restoration depended on the activity of the three-carbon part of the Glycolysis</span>/Gluconeogenesis pathway and occurred in both glycolytic and gluconeogenic regimens. Restoration took place abruptly over a narrow range of expression of genes in the three-carbon part of Glycolysis</span>. However, the absolute value of this range varied greatly with the allele in question. Finally, restoration of cell viability did not appear to be the result of a decrease in growth rate or an induction of major stress responses. CONCLUSIONS/SIGNIFICANCE: Our findings provide the first evidence for a genetic system that connects DNA chain elongation to Glycolysis</span>. Its role may be to modulate some aspect of DNA synthesis in response to the energy provided by the environment and the underlying mechanism is discussed. It is proposed that related systems are ubiquitous.

Increased production of pyruvic acid by Escherichia coli RNase G mutants in combination with cra mutations.

//www.hubmed.org/fulltext.cgi?uids=17483940">Appl Microbiol Biotechnol</a>. 2007 Aug; 76(1): 183-92
Sakai T, Nakamura N, Umitsuki G, Nagai K, Wachi M

The Escherichia coli RNase G is known as an endoribonuclease responsible for the 5'-end maturation of 16S rRNA and degradation of several specific mRNAs such as adhE and eno mRNAs. In this study, we found that an RNase G mutant derived from the MC1061 strain did not grow on a glucose minimal medium. Genetic analysis revealed that simultaneous defects of cra and ilvIH, encoding a transcriptional regulator of Glycolysis</span>/Gluconeogenesis and one of isozymes of acetohydroxy acid synthase, respectively, were required for this phenomenon to occur. The results of additional experiments presented here indicate that the RNase G mutation, in combination with cra mutation, caused the increased production of pyruvic acid from glucose, which was then preferentially converted to valine due to the ilvIH mutation, resulting in depletion of isoleucine. In fact, the rng cra double mutant produced increased amount of pyruvate in the medium. These results suggest that the RNase G mutation could be applied in the breeding of producer strains of pyruvate and its derivatives such as valine.

Functional genome-wide analysis of antibody producing NS0 cell line cultivated at different temperatures.

//www.hubmed.org/fulltext.cgi?uids=17421047">Biotechnol Bioeng</a>. 2007 Oct 15; 98(3): 616-30
Swiderek H, Al-Rubeai M

Lowering culture temperature has been reported as a significant factor in the improvement of mammalian cell productivity. To determine the physiological changes which take place at different temperature cultivations, an NS0 cell line producing human-mouse chimeric antibody was cultured at 22, 34 and 37 degrees C. Various cellular parameters such as viability, productivity, metabolism, apoptosis and cell cycle were studied and notable changes were shown to be accompanied by changes in metabolic rates. Reduction of the temperature to 22 degrees C resulted in a decrease in the growth rate, inhibition of antibody production, arrest of cell cycle in G2 phase and delay in apoptosis. A slight increase in antibody production was observed at 34 degrees C due to the increase of growth rate and prolonged stationary phase. To better understand and explore the mechanisms underpinning these biological alterations and to identify the genes involved in the genetic reprogramming, genome-wide analyses were performed using GeneChip Mouse Genome arrays. The examination of differential gene expression induced by temperature reduction demonstrated a specific pattern of gene expression in NS0 cells in response to temperature stress. The effect of temperature on transcription induced changes within a wide range of genes involved in metabolic and signalling pathways. Most deregulated genes involved in essential metabolic pathways (i.e. Glycolysis</span>/Gluconeogenesis, pentose phosphate pathway and inositol metabolism) were repressed in cells cultured at 22 degrees C. By combining gene expression and physiological changes at different temperatures it was possible to provide greater understanding of cell response to hypothermic conditions.

Proteomic analysis of Saccharomyces cerevisiae under high gravity fermentation conditions.

//www.hubmed.org/fulltext.cgi?uids=17137342">J Proteome Res</a>. 2006 Dec; 5(12): 3411-9
Pham TK, Chong PK, Gan CS, Wright PC

Saccharomyces cerevisiae KAY446 was utilized for ethanol production, with glucose concentrations ranging from 120 g/L (normal) to 300 g/L (high). Although grown in a high glucose environment, S. cerevisiae still retained the ability to produce ethanol with a high degree of glucose utilization. iTRAQ-mediated shotgun proteomics was applied to identify relative expression change of proteins under the different glucose conditions. A total of 413 proteins were identified from three replicate, independent LC-MS/MS runs. Unsurprisingly, many proteins in the Glycolysis</span>/Gluconeogenesis pathway showed significant changes in expression level. Twenty five proteins involved in amino acid metabolism decreased their expression, while the expressions of 12 heat-shock related proteins were also identified. Under high glucose conditions, ethanol was produced as a major product. However, the assimilation of glucose as well as a number of byproducts was also enhanced. Therefore, to optimize the ethanol production under very high gravity conditions, a number of pathways will need to be deactivated, while still maintaining the correct cellular redox or osmotic state. Proteomics is demonstrated here as a tool to aid in this forward metabolic engineering.

Downregulation in components of the mitochondrial electron transport chain in the postmortem frontal cortex of subjects with bipolar disorder.

//www.hubmed.org/fulltext.cgi?uids=16699605">J Psychiatry Neurosci</a>. 2006 May; 31(3): 189-96
Sun X, Wang JF, Tseng M, Young LT

OBJECTIVE: Many studies indicate a genetic predisposition to bipolar disorder (BD) and suggest that a number of abnormal genes are involved in its development. In this study, we used DNA microarray technology to analyze gene-expression profiles in the postmortem frontal cortex of subjects with BD. METHODS: Microarray hybridization was performed using human 19K microarray with universal human reference RNA in each hybridization. The reference cDNA was labelled with Cy3 and experimental cDNA, with Cy5. Glass array slides were cohybridized with equal amounts of mixed reference and experimental cDNA. Selected gene targets were further verified using real-time polymerase chain reaction (PCR). RESULTS: We found that 831 genes were differentially expressed in subjects with BD, including a number of genes in the mitochondrial electron transport chain (ETC), phosphatidylinositol-signalling system and Glycolysis</span>/ Gluconeogenesis. Eight genes coding for the components of the mitochondrial ETC were identified along with 15 others related to mitochondrial function. Downregulation of NADH-ubiquinone oxidoreductase 20-kd subunit (ETC complex I), cytochrome c oxidase polypeptide Vic (ETC complex IV) and ATP synthase lipid-binding protein (ETC complex V) were further verified by real-time PCR. We also found that the expression of the NADH-ubiquinone oxidoreductase 20-kd subunit was increased in subjects with BD who were receiving mood-stabilizing treatment with lithium at the time of death, when compared with subjects with BD who were not being treated with lithium. CONCLUSIONS: Because the mitochondrial ETC is a major source for the generation of reactive oxygen species, these findings suggest that oxidative damage may play an important role in the pathophysiology of BD and that neuroprotection against this damage may be involved in the effect of lithium treatment.