SUBSYSTEM: Phenylalanine, tyrosine, and tryptophan biosynthesis (aromatic amino acids)
1-phosphatidyl-1D-myo-inositol 3-phosphates
SUBSYSTEM: Glycine, serine, and threonine metabolism
SUBSYSTEM: Glyoxalate and dicarboxylate metabolism
Methionyl-tRNA synthetase, mitochondrial
Dihydroneopterin triphosphate pyrophosphorylase
Transport of nucleosides and deoxynucleoside, extracellular
SUBSYSTEM: Branched chain amino acid metabolism (valine, leucine, and isoleucine)
Branched-chain-amino-acid aminotransferase, mitochondrial
Valine/tyrosine/tryptophan amino-acid permease
Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase
SUBSYSTEM: Nicotinic acid synthesis from TRP
Acetolactate synthase catalytic subunit, mitochondrial
Mitochondrial 3-oxoacyl-[acyl-carrier-protein] reductase
SUBSYSTEM: Mitochondrial type II fatty acid synthase
Phosphoribosylglycinamide formyltransferase
SUBSYSTEM: Thiamine (vitamin B1) metabolism
Mitochondrial phosphate carrier protein 2
D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate
Transport of phosphatidate, mitochondrial
Branched-chain-amino-acid aminotransferase, cytosolic
Very long-chain fatty acyl-CoA synthetase
Transport of deoxyuridine, extracellular
Transport of S-adenosyl-L-homocysteine, mitochondrial
Model-specific reaction, used to group lipid formation for biomass production (nitrogen limited)
SUBSYSTEM: Glycerol metabolism (glycerolipid metabolism)
SUBSYSTEM: Pantothenate and CoA metabolism
Model-specific reaction, used to affect NADH levels by converting NAD+ to NADH
1-phosphatidyl-1D-myo-inositol 3,5-bisphosphates
Model-specific reaction, used to affect ATP levels by converting ADT to ATP
3-phosphoshikimate 1-carboxyvinyltransferase
Peroxisomal 2,4-dienoyl-CoA reductase SPS19
SUBSYSTEM: Cytosolic fatty acid synthesis
Enoyl-[acyl-carrier-protein] reductase [NADH]
Acyl-[acyl-carrier-protein] transporter, mitochondrial
Glucosamine--fructose-6-phosphate aminotransferase [isomerizing]
SUBSYSTEM: Glutamate metabolism (aminosugars metabolism)
Indoleamine 2,3-dioxygenase family protein
Dolichyl-phosphate-mannose--protein mannosyltransferase 2
Model-specific reaction, involved in sphingoglycolipid metabolism
Transport of deoxyadenosine, extracellular
3-oxoacyl-[acyl-carrier-protein] synthase
UDP-N-acetylglucosamine pyrophosphorylase
Transport of dicarboxylates, extracellular
5-aminolevulinate synthase, mitochondrial
3-oxoacyl-[acyl-carrier-protein] synthase homolog
SUBSYSTEM: Fructose and mannose metabolism
Para-hydroxybenzoate--polyprenyltransferase, mitochondrial
1-phosphatidyl-1D-myo-inositol 4-phosphates
Succinyl-CoA ligase [ADP-forming] subunit alpha, mitochondrial
3-hydroxy-3-methylglutaryl-coenzyme A reductase 1
Succinate dehydrogenase [ubiquinone] cytochrome b subunit, mitochondrial
Phosphoribosylaminoimidazolecarboxamide formyltransferase
Transport of (R)-mevalonate, mitochondrial
Enoyl-[acyl-carrier protein] reductase [NADPH, B-specific], mitochondrial
SUBSYSTEM: Alanine and aspartate metabolism
Transport of deoxycytidine, extracellular
3-hydroxyacyl-[acyl-carrier-protein] dehydrase
Mitochondrial aspartate-glutamate transporter AGC1
Phosphatidylserine decarboxylase proenzyme 2
Transport of oxidized glutathione, extracellular
SUBSYSTEM: Pyridoxine (vitamin B6) metabolism
Homoisocitrate dehydrogenase, mitochondrial
Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating
Glycerophosphoinositol plasma membrane permease
Pyruvate dehydrogenase E1 component subunit alpha, mitochondrial
5',5'''-P-1,P-4-tetraphosphate phosphorylase
3',5'-cyclic-nucleotide phosphodiesterase 2
Hydroxyacylglutathione hydrolase, cytoplasmic isozyme
Model-specific reaction, pools acyl-CoAs
Saccharopine dehydrogenase [NAD+, L-lysine-forming]
Transport of pantetheine 4'-phosphate, mitochondrial
Probable alanine aminotransferase, mitochondrial
Probable glutamyl-tRNA(Gln) amidotransferase subunit A, mitochondrial
Choline/ethanolaminephosphotransferase 1
CDP-diacylglycerol--inositol 3-phosphatidyltransferase
Uroporphyrinogen-III C-methyltransferase
Transport of acetaldehyde, extracellular
Excretion of nicotinamide mononucleotide
Phosphatidylglycerol phosphate phosphatase A
Chalmers University of Technology, Gothenburg
Transport of 8-amino-7-oxononanoate, extracellular
[Acyl-carrier-protein] acetyltransferase
Ubiquinone biosynthesis monooxygenase COQ6
3-ketodihydrosphingosine reductase TSC10
Transport of 3-methyl-2-oxopentanoate, mitochondrial
Dolichyl-phosphate-mannose--protein mannosyltransferase 1
Model-specific reaction, involved in the elongation of fatty acids
Potassium-activated aldehyde dehydrogenase, mitochondrial
Succinate-semialdehyde dehydrogenase [NADP+]
CDP-diacylglycerol--serine O-phosphatidyltransferase
Imidazole glycerol phosphate synthase hisHF
(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl trihydrogen diphosphate
Carboxylic acid transporter protein homolog
Transport of 2-oxoadipate, mitochondrial
Inositol-1,4,5-trisphosphate 5-phosphatase 3
Putative mitochondrial carnitine O-acetyltransferase
Ribonucleoside-diphosphate reductase large chain 1
1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase 1
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphates
Dihydroxy-acid dehydratase, mitochondrial
D-arabinose dehydrogenase [NAD(P)+] heavy chain
Inositol-1,4,5-trisphosphate 5-phosphatase
Probable 1-acyl-sn-glycerol-3-phosphate acyltransferase
N-acetyl-gamma-glutamyl-phosphate reductase
Glycerol uptake/efflux facilitator protein
Inositol-1,4,5-trisphosphate 5-phosphatase 4
Model-specific reaction, used to group lipid formation for biomass production (carbon limited)
Transport of (S)-3-hydroxy-3-methylglutaryl-CoA, mitochondrial
UTP--glucose-1-phosphate uridylyltransferase
2-dehydro-3-deoxy-D-arabino-heptonate 7-phosphate
Nicotinamide-nucleotide adenylyltransferase 1
7-keto 8-aminopelargonic acid transporter
Probable inosine-5'-monophosphate dehydrogenase IMD3
Ketol-acid reductoisomerase, mitochondrial
Transport of a-ketoglutarate, extracellular
Serine hydroxymethyltransferase, mitochondrial
Glycine dehydrogenase [decarboxylating], mitochondrial
Nicotinate-nucleotide pyrophosphorylase [carboxylating]
Dihydroxyacetone phosphate acyltransferase 1
L-aminoadipate-semialdehyde dehydrogenase
SUBSYSTEM: Starch and sucrose metabolism
Peroxisomal acyl-coenzyme A thioester hydrolase 1
S-(hydroxymethyl)glutathione dehydrogenase
1,3-beta-D-glucan-UDP glucosyltransferase
Probable prolyl-tRNA synthetase, mitochondrial
Tryptophanyl-tRNA synthetase, cytoplasmic
SUBSYSTEM: Proteins, peptides and amino acids metabolism
Transport of glyceraldehyde, extracellular
Transport of acetoacetate, mitochondrial
Asparagine synthetase [glutamine-hydrolyzing] 1
Aspartate aminotransferase, mitochondrial
Mitochondrial 2-oxodicarboxylate carrier 2
Inositol phosphosphingolipids phospholipase C
Glycylpeptide N-tetradecanoyltransferase
Dolichyl-phosphate-mannose--protein mannosyltransferase 4
3-oxoacyl-[acyl-carrier-protein] reductase
Isoleucyl-tRNA synthetase, mitochondrial
Glucosamine 6-phosphate N-acetyltransferase
Transport of D-glucosamine 6-phosphate, extracellular
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase
Transport of 7,8-diaminononanoate, extracellular
Uptake of 5alpha-ergosta-7,22-dien-3beta-ol
Glycerol-3-phosphate dehydrogenase, mitochondrial
5-amino-6-(5-phosphoribosylamino)uracil reductase
Mannosyl phosphorylinositol ceramide synthase SUR1
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
Uptake of ergosta-5,7,22,24(28)-tetraen-3beta-ol
Dihydrosphingosine 1-phosphate phosphatase
Transport of 3-methyl-2-oxobutanoate, mitochondrial
CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase
Excretion of adenosine 3',5'-bisphosphate
Transport of S-adenosyl-L-methionine, mitochondrial
Phosphoribosylformylglycinamidine cyclo-ligase
Phosphopantothenate-cysteine decarboxylase
Transport of 4-methyl-2-oxopentanoate, mitochondrial
Asparaginyl-tRNA synthetase, mitochondrial
External NADH-ubiquinone oxidoreductase 2, mitochondrial
Methionyl-tRNA formyltransferase, mitochondrial
Geranylgeranyl transferase type-2 subunit beta
Phospho-2-keto-3-deoxyheptonate aldolase
Phenylalanyl-tRNA synthetase alpha chain
N-terminal acetyltransferase A complex subunit NAT1
Transport of dethiobiotin, mitochondrial
Glyceraldehyde-3-phosphate dehydrogenase 1
Hexaprenyl pyrophosphate synthetase, mitochondrial
Methylene-fatty-acyl-phospholipid synthase
Tryptophanyl-tRNA synthetase, mitochondrial
Trehalose synthase complex regulatory subunit TPS3
Inosine-5'-monophosphate dehydrogenase IMD2
Phospholipid:diacylglycerol acyltransferase
Dihydroxyacetone phosphate acyltransferase 2
Dolichyl-phosphate-mannose--protein mannosyltransferase 3
ATP drain flux for constant maintanence requirements
[Acyl-carrier-protein] malonyltransferase
Transport of 2-acetolactate, mitochondrial
Isocitrate dehydrogenase [NADP], mitochondrial
Galactose-1-phosphate uridylyltransferase
Ubiquinone biosynthesis methyltransferase COQ5, mitochondrial
Phosphatidylserine decarboxylase proenzyme 1, mitochondrial
Transport of 3-isopropylmalate, mitochondrial
Carbamoyl-phosphate synthase arginine-specific large chain
(2S)-2-[5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamido]succinic acid
Transport of deoxyguanosine, extracellular
Ethanolamine-phosphate cytidylyltransferase
Hydroxyacylglutathione hydrolase, mitochondrial
Succinate/fumarate mitochondrial transporter
Trehalose synthase complex regulatory subunit TSL1
1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate
N-(5'-phosphoribosyl)anthranilate isomerase
This is a reconstruction of the metabolic network of the yeast Saccharomyces cerevisiae as described in the article: The genome-scale metabolic model iIN800 of Saccharomyces cerevisiae and its validation: a scaffold to query lipid metabolism. Nookaew I, Jewett MC, Meechai A, Thammarongtham C, Laoteng K, Cheevadhanarak S, Nielsen J, Bhumiratana S. BMC Syst Biol. 2008 Aug 7;2:71; PMID: 18687109 ,doi: 10.1186/1752-0509-2-71 Abstract: BACKGROUND: Up to now, there have been three published versions of a yeast genome-scale metabolic model: iFF708, iND750 and iLL672. All three models, however, lack a detailed description of lipid metabolism and thus are unable to be used as integrated scaffolds for gaining insights into lipid metabolism from multilevel omic measurement technologies (e.g. genome-wide mRNA levels). To overcome this limitation, we reconstructed a new version of the Saccharomyces cerevisiae genome-scale model, iIN800 that includes a more rigorous and detailed description of lipid metabolism. RESULTS: The reconstructed metabolic model comprises 1446 reactions and 1013 metabolites. Beyond incorporating new reactions involved in lipid metabolism, we also present new biomass equations that improve the predictive power of flux balance analysis simulations. Predictions of both growth capability and large scale in silico single gene deletions by iIN800 were consistent with experimental data. In addition, 13C-labeling experiments validated the new biomass equations and calculated intracellular fluxes. To demonstrate the applicability of iIN800, we show that the model can be used as a scaffold to reveal the regulatory importance of lipid metabolism precursors and intermediates that would have been missed in previous models from transcriptome datasets. CONCLUSION: Performing integrated analyses using iIN800 as a network scaffold is shown to be a valuable tool for elucidating the behavior of complex metabolic networks, particularly for identifying regulatory targets in lipid metabolism that can be used for industrial applications or for understanding lipid disease states. The SBML was downloaded from the BioMet Toolbox page( http://129.16.106.142/models.php?c=S.cerevisiae ) of Jens Nielsen's Lab for Systems Biology at Chalmers University ( http://www.sysbio.se/ ). The parameters LOWER_BOUND and UPPER_BOUND were added as defined in the BioOpt file available from the same page. One error was corrected R_PIxtO (Excretion of phosphate) LOWER_BOUND was changed from 1000 to 0. Parameters FLUX_VALUE were then calculated as defined in "Flux balance analysis: a geometric perspective.", Smallbone K and Simeonidis E, 2009 (J Theor Biol. 2009;258(2):311-5, pmid: 19490860 ). Technical notes: The compartments included here have no volume defined; there are no reliable estimates available for those volumes yet. There are no kinetic functions defined for the reactions because this model only represents the chemical structure of the network (stoichiometry). Reactions for uptake and excretion are defined for some of the metabolites. All uptake reactions are constrained to zero flux and all excretion reactions are unconstrained. All genes are assigned to the cytosol. This has no physiological meaning, but it is necessary for the structure of the model. Biomass equations are available for carbon-limited and nitrogen-limited growth. The nitrogen-limited biomass equation is constrained to zero flux. A few reactions are meant to be used to simulate the effect of for example increased ATP production. They are constrained to zero flux. This SBML representation of the yeast metabolic network is made available under the Creative Commons Attribution-Share Alike 3.0 Unported Licence (see www.creativecommons.org ). This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not. . To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
Glutamine-dependent carbamoyl-phosphate synthase
Hypoxanthine-guanine phosphoribosyltransferase
Phosphoribosylformylglycinamidine synthase
3',5'-cyclic-nucleotide phosphodiesterase 1
Glycerophosphodiester phosphodiesterase GDE1
Transport of hypoxanthine, extracellular
Transport of (R)-2-oxoisovalerate, mitochondrial
2-octaprenyl-6-methoxyphenol hydroxylase
Mitochondrial 2-oxodicarboxylate carrier 1
a-ketoglutarate/malate translocator, extracellular
Succinyl-CoA ligase [ADP-forming] subunit beta, mitochondrial
Phosphatidylethanolamine N-methyltransferase
Transport of arabinose (low affinity), extracellular
Mannosyl phosphorylinositol ceramide synthase regulatory protein CSG2
Putative inosine-5'-monophosphate dehydrogenase-like protein
Transport of dihydrofolate, mitochondrial
1-phosphatidylinositol-3-phosphate 5-kinase FAB1
S-adenosylmethionine decarboxylase proenzyme
Transport of a-methylglucoside, extracellular
NADH-ubiquinone oxidoreductase, mitochondrial
Deoxyuridine 5'-triphosphate nucleotidohydrolase
Probable phosphatidylinositol-4-phosphate 5-kinase MSS4
Uptake of glycerophosphatidyl-D-myo-inositol
Mitochondrial thiamine pyrophosphate carrier 1
Asparaginyl-tRNA synthetase, cytoplasmic
Putative inosine-5'-monophosphate dehydrogenase IMD1
D-lactate dehydrogenase [cytochrome] 1, mitochondrial
Isocitrate dehydrogenase [NADP], cytoplasmic
Glycerol-3-phosphate dehydrogenase [NAD+] 2, mitochondrial
Inositolphosphorylceramide-B C-26 hydroxylase
Transport of deoxyinosine, extracellular
Excretion of glycerophosphatidyl-D-myo-inositol
High-affinity potassium transport protein
Phosphoadenosine phosphosulfate reductase
NAD-dependent malic enzyme, mitochondrial
Transport of O-acetylcarnitine, mitochondrial
Probable inosine-5'-monophosphate dehydrogenase IMD4
ATP synthase subunit alpha, mitochondrial
6-phosphogluconate dehydrogenase, decarboxylating 2
Probable UTP--glucose-1-phosphate uridylyltransferase
Transport of 5,10-methylenetetrahydrofolate, mitochondrial
Excretion of ergosta-5,7,22,24(28)-tetraen-3beta-ol
Cytochrome b-c1 complex subunit Rieske, mitochondrial
Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial
Glycerol-3-phosphate O-acyltransferase 2
Mitochondrial oxaloacetate transport protein
Dolichyl-phosphate-mannose--protein mannosyltransferase 6
3,4-dihydroxy-2-butanone-4-phosphate synthase
Inorganic pyrophosphatase, mitochondrial
Transport of 5-phospho-alpha-D-ribose 1-diphosphate, mitochondrial
Glycerol-3-phosphate O-acyltransferase 1
Transport of pyridine-2,3-dicarboxylate, mitochondrial
Glyceraldehyde-3-phosphate dehydrogenase 3
Hexaprenyldihydroxybenzoate methyltransferase, mitochondrial
Transport of carbon dioxide, extracellular
1-phosphofructokinase (fructose 1-phosphate kinase)
Sulfite reductase [NADPH] flavoprotein component
Model-specific reaction, used to affect NADPH levels by converting NADP+ to NADPH
Asparagine synthetase [glutamine-hydrolyzing] 2
Phosphoribosylaminoimidazole-succinocarboxamide synthase
Transport of N-acetylglucosamine, extracellular
Malonyl CoA-acyl carrier protein transacylase, mitochondrial
Transport of tetrahydrofolate, mitochondrial
Protein farnesyltransferase subunit beta
Excretion of 5alpha-ergosta-7,22-dien-3beta-ol
NADPH-dependent 1-acyldihydroxyacetone phosphate reductase
Isocitrate dehydrogenase [NAD] subunit 1, mitochondrial
Transport of 2-isopropylmalate, mitochondrial
Transport of nicotinamide mononucleotide, extracellular
Transport of pimelic acid, extracellular
Serine hydroxymethyltransferase, cytosolic
Glycerol-3-phosphate dehydrogenase [NAD+] 1
Acetylornithine aminotransferase, mitochondrial
Dihydrolipoyl dehydrogenase, mitochondrial
3-methyl-2-oxobutanoate hydroxymethyltransferase
Saccharopine dehydrogenase [NADP+, L-glutamate-forming]
6-phosphogluconate dehydrogenase, decarboxylating 1
Transport of adenosine 3',5'-bisphosphate, extracellular
Phenylalanyl-tRNA synthetase, mitochondrial
Ribonucleoside-diphosphate reductase large chain 2
Carnitine O-acetyltransferase, mitochondrial
Methylenetetrahydrofolate dehydrogenase [NAD+]
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase
Protoheme IX farnesyltransferase, mitochondrial
Phosphatidylinositol kinase homolog TOR1
Dolichyl-phosphate-mannose--protein mannosyltransferase 5
Diacylglycerol pyrophosphate phosphatase 1
2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
Transport of glycerone phosphate, mitochondrial
3-hydroxy-3-methylglutaryl-coenzyme A reductase 2
External NADH-ubiquinone oxidoreductase 1, mitochondrial
Glyceraldehyde-3-phosphate dehydrogenase 2
Phosphatidylinositol 4,5-bisphosphate 5-phosphatase
Phosphoribosylaminoimidazole carboxylase
Adenosylmethionine-8-amino-7-oxononanoate aminotransferase
Transport of sn-glycerol 3-phosphate, mitochondrial
Uncharacterized seryl-tRNA synthetase, cytoplasmic
Magnesium-activated aldehyde dehydrogenase, cytosolic