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HumanCyc Release Notes History

HumanCyc Statistics
October 11, 2013 Description
Pathways 293 Number of metabolic and signaling pathways, excluding super-pathways
Reactions 2582 Number of reactions
Genes 20892 Number of genes
Polypeptides 20629 Number of polypeptides
Protein complexes 341 Number of protein complexes
Enzymes 3765 Number of enzymes
Transporters 451 Number of transporters
Chemical compounds 1657 Number of chemical compounds
Citations 40551 Number of citations to the scientific literature
 

Release Notes for HumanCyc Version 18.1

Released on Jun 23, 2014

Since the last release we have added six new pathways to HumanCyc. These include a novel threonine degradation pathway in humans, an alternate lysine degradation pathway via pipecolate, carnosine and homocarnosine biosynthesis, fructose 2,6-bisphosphate metabolism and hydrogen sulfide biosynthesis. We also revised 10 existing pathways in HumanCyc, which include ubiquinol 10, taurine, asparagine and coenzyme A biosynthesis; glycine betaine, purines, beta alanine, asparagine and valine degradation; and the superpathway of choline degradation to serine. HumanCyc was also updated by propagation of new data from MetaCyc.

New Pathways

  • threonine degradation
  • hydrogen sulfide biosynthesis (trans-sulfuration)
  • lysine degradation II (pipecolate pathway)
  • fructose 2,6-bisphosphate synthesis/dephosphorylation
  • homocarnosine degradation
  • carnosine degradation

    Revised pathways:

  • glycine betaine degradation
  • superpathway of choline degradation to L-serine
  • asparagine degradation
  • asparagine biosynthesis
  • coenzyme A biosynthesis
  • taurine biosynthesis
  • purine deoxyribonucleosides degradation
  • beta alanine degradation
  • valine degradation
  • ubiquinol-10 biosynthesis

    Release Notes for HumanCyc Version 18.0

    Released on March 24, 2014

    Since the last release we have added two new pathways to HumanCyc which show an alternate biosynthetic pathway for putrescine and a superpathway to demonstrate choline degradation to L-serine. We also revised 24 existing pathways in HumanCyc.These include several degradation pathways for pyrimidines, uracil, 4-hydroxyproline, tryptophan, 2-oxobutanoate, histamine, glutamate, glycine betaine and lysine; fatty acid biosynthesis and the biosynthesis of glutamate, NAD, ornithine and L-carnitine; the mitochondrial L-carnitine shuttle, acyl carrier protein metabolism, the oxidative branch of the pentose phosphate pathway, sulfite oxidation, the GABA shunt, glutathione redox reactions I and II, folate transformations, 2-oxoglutarate decarboxylation to succinyl coA and sulfate activation. HumanCyc was also updated by propagation of new data from MetaCyc.

    New Pathways

  • putrescine biosynthesis II
  • choline degradation to L-serine

    Revised pathways:

  • 4-hydroxyproline degradation
  • pentose phosphate pathway (oxidative branch)
  • NAD phosphorylation and dephosphorylation II
  • tryptophan degradation
  • glutamate biosynthesis/degradation
  • ornithine de novo biosynthesis
  • glutathione redox reactions II
  • glutathione redox reactions I
  • mitochondrial L-carnitine shuttle
  • fatty acid biosynthesis initiation
  • 2-oxobutanoate degradation
  • sulfite oxidation
  • histamine degradation
  • acyl carrier protein metabolism
  • NAD de novo biosynthesis
  • GABA shunt
  • glycine betaine degradation
  • folate transformations
  • L-carnitine biosynthesis
  • 2-oxoglutarate degradation to succinyl coA
  • lysine degradation
  • sulfate activation for sulfonation
  • pyrimidine deoxyribonucleosides degradation
  • uracil degradation

    Release Notes for HumanCyc Version 17.5

    Released on October 11, 2013

    Since the last release we have added two new pathways to HumanCyc, which cover the salvage of tetrahydrobioterin and purine nucleotides. We also revised 10 existing pathways, which include the malate aspartate shuttle, biosynthesis of the amino acids serine and glycine and NAD salvage.
    HumanCyc was also upgraded by propagation of relevant data updates from MetaCyc.

    New pathways:

  • purine nucleotide salvage
  • tetrahydrobiopterin salvage

    Revised pathways:

  • cysteine biosynthesis /homocysteine degradation
  • Glyine biosynthesis I
  • glycine biosynthesis II
  • glycine biosynthesis III
  • glycine cleavage
  • malate aspartate shuttle
  • NAD salvage
  • serine and glycine biosynthesis
  • serine biosynthesis (phosphorylated route)
  • tetrapyrrole biosynthesis

    Release Notes for HumanCyc Version 17.1

    Released on June 11, 2013

    Since the last release we have added 5 new pathways to HumanCyc, all of which were imported from MetaCyc. We also revised 4 existing pathways. The new pathways cover purine nucleotide and deoxynucleotide biosynthesis and salvage. Pathway curation in HumanCyc was facilitated by importing some compounds from MetaCyc to enable computational instantiation. HumanCyc was also upgraded by propagation of relevant data updates from MetaCyc.

    New pathways:

  • adenosine deoxyribonucleotides de novo biosynthesis I
  • adenosine ribonucleotides de novo biosynthesis
  • guanosine deoxyribonucleotides de novo biosynthesis I
  • guanosine ribonucleotides de novo biosynthesis
  • purine deoxyribonucleosides salvage

    Revised pathways:

  • glycogenolysis
  • pyruvate decarboxylation to acetyl CoA
  • serotonin and melatonin biosynthesis
  • ceramide de novo biosynthesis

    Release Notes for HumanCyc Version 17.0

    Released on March 28, 2013

    Since the last release we have added 17 new pathways and three super pathways to HumanCyc, most of which were imported from MetaCyc. We also revised 5 existing pathways.

    The coverage of nucleotide and nucleoside phosphorylation, biosynthesis and degradation was significantly enhanced by the addition of several new pathways.
    Other new pathways curated include the degradation of phytol, a metabolite derived from chlorophyll, the peroxisomal β oxidation of fatty acids and the biosynthesis of novel anti-inflammatory compounds derived from omega 3 and 6 fatty acids.

    Pathway curation in HumanCyc was facilitated by importing some compounds from MetaCyc to enable computational instantiation. HumanCyc was also upgraded by propagation of relevant data updates from MetaCyc.

    New pathways:

  • aspirin triggered lipoxin biosynthesis
  • aspirin triggered resolvin D biosynthesis
  • aspirin triggered resolvin E1 biosynthesis
  • CMP phosphorylation
  • fatty acid β-oxidation VI (peroxisome)
  • phytol degradation
  • purine deoxyribonucleosides degradation
  • pyrimidine deoxyribonucleosides degradation
  • pyrimidine deoxyribonucleotide phosphorylation
  • pyrimidine deoxyribonucleotides de novo biosynthesis I
  • pyrimidine deoxyribonucleotides de novo biosynthesis II
  • pyrimidine deoxyribonucleotides biosynthesis from CTP
  • pyrimidine ribonucleosides salvage I
  • resolvin D biosynthesis
  • UTP and CTP de novo biosynthesis
  • UTP and CTP dephosphorylation I
  • UTP and CTP dephosphorylation II

    New super pathways

  • superpathway of pyrimidine deoxyribonucleoside salvage
  • superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis
  • superpathway of pyrimidine ribonucleosides degradation

    Revised pathways:

  • C20 prostanoid biosynthesis
  • eumelanin biosynthesis
  • fatty acid α-oxidation II
  • fatty acid α-oxidation III
  • pyrimidine deoxyribonucleosides salvage

    Release Notes for HumanCyc Version 16.5

    Released on Nov 14, 2012

    We curated two new pathways in HumanCyc that describe the peroxisomal α-oxidation of 3-methyl branched fatty acids and 2-hydroxylated straight chain fatty acids. We also imported a pathway from MetaCyc for the detoxification of 4-hydroxy-2-nonenal, a product of lipid peroxidation.

    Several compounds were imported into HumanCyc from MetaCyc in order to allow computational instantiation of the two new fatty acid α-oxidation pathways, as well as the existing pathway fatty acid β-oxidation III (unsaturated, odd number).

    Also for this release, HumanCyc has also been upgraded by propagation of the latest data updates from MetaCyc.

    New pathways curated in HumanCyc:

  • fatty acid α-oxidation II
  • fatty acid α-oxidation III

    Pathways added from MetaCyc:

  • 4-hydroxy-2-nonenal detoxification

    Release Notes for HumanCyc Version 16.0

    Released on Feb 21, 2012

    Further refinements of the HumanCyc flux-balance analysis (FBA) model, including reaction balancing, structure modifications, instantiations of compound classes and addition of reactions from MetaCyc have occurred in this version of HumanCyc.

    We have also added the following pathways from MetaCyc:

  • 4-hydroxyphenylpyruvate biosynthesis
  • adenine and adenosine salvage I
  • adenine and adenosine salvage III
  • adenine and adenosine salvage VI
  • aspartate biosynthesis
  • calcium transport I
  • dTMP de novo biosynthesis
  • fatty acid β-oxidation III (unsaturated, odd number)
  • fatty acid biosynthesis initiation II
  • glutamine degradation I
  • glycine biosynthesis II
  • guanine and guanosine salvage I
  • histidine degradation VI
  • methylglyoxal degradation VI
  • morphine biosynthesis
  • NADH repair
  • oxidized GTP and dGTP detoxification
  • phenylethylamine degradation I
  • phosphatidylethanolamine biosynthesis III
  • proline biosynthesis I
  • purine ribonucleosides degradation to ribose-1-phosphate
  • putrescine biosynthesis III
  • S-methyl-5'-thioadenosine degradation II
  • S-methyl-5-thio-α-D-ribose 1-phosphate degradation
  • (S)-reticuline biosynthesis II
  • superpathway of inositol phosphate compounds
  • tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate
  • thiamin salvage III
  • tRNA splicing
  • UDP-N-acetyl-D-galactosamine biosynthesis I
  • UDP-N-acetyl-D-galactosamine biosynthesis II

    Release Notes for HumanCyc Version 15.5

    Released on October 17, 2011.

    Further refinements of the HumanCyc flux-balance analysis (FBA) model have occurred in this version of HumanCyc. This model can be executed by downloading a configuration of the Pathway Tools software (Linux-64 version) that includes HumanCyc.

    Release Notes for HumanCyc Version 15.1

    Released on June 8, 2011.

    With this release we have completed the FBA modeling of HumanCyc, including reaction balancing, structure modifications, instantiations of compound classes and addition of reactions from MetaCyc.

    We have also added the following human metabolic pathways from MetaCyc:
  • (S)-reticulline biosynthesis
  • adenine and adenosine salvage I
  • adenine and adenosine salvage pathway III
  • adenine and adenosine salvage IV
  • aspartate biosynthesis pathway
  • fatty acid biosynthesis initiation II
  • glutamine degradation I
  • methylglyoxal degradation VI
  • morphine biosynthesis
  • phosphatikylethanolamine biosynthesis III
  • proline biosynthesis
  • purine ribonucleosides degradation to ribose-1-phosphate
  • superpathway of inositol phosphate compounds
  • tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate
  • thyronamine and iodothyronamine metabolism
  • tryphtophan degradation XI (mammalian, via kynurenine)

    Release Notes for HumanCyc Version 15.0

    Released on March 18, 2011.

    For this release, we have used a number of automated Pathway Tools to analyze the reactions and pathways of HumanCyc to interrogate the completeness of the metabolic network. These efforts are carried out in conjunction with the development of a Flux Balance Analysis (FBA) modeling capability for Pathway Tools. The creation of an FBA model for HumanCyc is ongoing, and any feedback would be appreciated.

    We have used the dead-end metabolite tool to identify compounds that are only reactants, or only products, of HumanCyc reactions. Such compounds are necessarily excluded from FBA models due to balance constraints. Therefore, any compounds that are truly only reactants in a metabolic network must be obligate nutrients (such as essential amino acids or vitamins) and should also have transport reactions. We have added some transport reactions of this type and will add more in future releases.

    Similarly, compounds that are only products cannot be further metabolized by the metabolic network and must be listed as secreted compounds and have defined (possibly orphan) transport reactions. Many such compounds in HumanCyc are likely metabolized further by reactions that have yet to be added to the HumanCyc metabolic network. Some of these transport and enzymatic reactions have been added, and more will be resolved subsequently.

    We have employed automated tools for identifying unbalanced reactions, as these will also be excluded from the FBA model. Chemical structure and stoichiometric corrections have resulted in properly balanced enzymatic reactions. More of these will be identified and resolved in future.

    Preliminary results from executing the FBA analysis of the HumanCyc metabolic network have identified enzymatic reactions and pathways in the MetaCyc database that were added to HumanCyc based on analysis of the scientific literature. We have also defined reaction directions as suggested by the FBA model followed by literature research.

    We have removed all legacy comments previously uploaded from locuslink, removed some deaccessioned EntrezGene links and repaired some other external links.

    Release Notes for HumanCyc Version 14.6

    With this release we have added 107 new transport reactions and newly assigned more than 300 proteins to these transport activities. We have added literature citations, evidence codes and comments to many of these transport activities, and will be expanding this aspect of the HumanCyc knowledge base in the future.

    We have also imported to HumanCyc more than 100 comments, literature citations and evidence codes for pathways originally curated in MetaCyc. These have been edited to focus on the Homo sapiens specific biology.

    Release Notes for HumanCyc Version 14.5

    Released on October 1, 2010.

    We are continuing with manual curation of the HumanCyc knowledge base of metabolic pathways. HumanCyc is still a work in progress; any constructive feedback will be greatly appreciated.

    With this release we have updated the genes and proteins content of HumanCyc such that it now contains the UniProt Complete Proteome for H. sapiens. This has included an automated update of names, synonyms and functional annotation of enzymes. We have also updated UniProt and EntrezGene identifiers and external links in HumanCyc.

    Additionally, we have created and curated the following pathways focused on lipid, steroid and proteoglycan metabolism. Pathways Created and Manually Curated for Version 14.5 include:

  • leukotriene biosynthesis
  • pregnenolone biosynthesis
  • androgen biosynthesis
  • estrogen biosynthesis
  • glucocorticoid biosynthesis
  • mineralocorticoid biosynthesis
  • glycoaminoglycan-protein linkage region biosynthesis
  • heparan sulfate biosynthesis (late stages)
  • heparan sulfate biosynthesis
  • chondroitin and dermatan biosynthesis
  • chondroitin sulfate biosynthesis (late stages)
  • dermatan sulfate biosynthesis (late stages)
  • chondroitin sulfate biosynthesis
  • dermatan sulfate biosynthesis
  • chondroitin sulfate degradation
  • dermatan sulfate degradation

    Release Notes for HumanCyc Version 14.1

    Released on June 16, 2010.

    Curation of the HumanCyc knowledge base continues in conjunction with the Pharmacometabolomics Research Network (PMRN). This is a multi-year collaboration to develop tools and provide resources for the metabolomics community; to this end we have focused on curation of information from the scientific literature concerning chemical compounds and enzymes of interest to the PMRN and the larger field of metabolomics.

    As a consequence of the unique capabilities of metabolomics measurements, particular emphasis will be placed on pathways of metabolism of xenobiotics, nutrients and metabolites produced by the gut Microbiome. As always, feedback and suggestions are welcome. New HumanCyc pathways for this release include:

  • ascorbate recycling (cytosolic)
  • eumelanin biosynthesis
  • melatonin degradation II
  • melatonin degradation III
  • superpathway of melatonin degradation
  • L-dopachrome biosynthesis
  • ketogenesis
  • ketolysis
  • sucrose degradation
  • flavin biosynthesis

    Release Notes for HumanCyc Version 14.0

    Released on March 18, 2010.

    We have recently begun a more intensive manual curation of the HumanCyc knowledge base with the intent of developing a fully curated database of human metabolic pathways. These efforts are anticipated to span years, and hence, HumanCyc is still a work in progress. Any constructive feedback will be greatly appreciated.

    We have initially focused on updating the current content of HumanCyc. This has included an automated update of names and functional annotation of genes and proteins from the UniProt Complete Proteome for H. sapiens (using a version downloaded on 11/11/2009). We have also updated Ensembl identifiers in HumanCyc to reflect the latest Ensembl identifiers from version 56. We have also updated the UniProt and Ensembl external links in HumanCyc. In general, HumanCyc has undergone extensive housecleaning so as to represent the latest publicly available gene functions.

    Additionally, we have developed a Pathway Tools Signaling Pathway Editor that debuts with this version; demonstration pathways have been created for MAP kinase and BMP intracellular signaling.

    Pathways newly created and manually curated for Version 14.0 include:

  • bile acid biosynthesis, neutral pathway
  • 1,25-dihydroxyvitamin D3 biosynthesis
  • L-carnitine biosynthesis
  • mitochondrial L-carnitine shuttle pathway
  • spermine and spermidine degradation
  • dolichol and dolichyl phosphate biosynthesis
  • CMP-N-acetylneuraminate biosynthesis I (eukaryotes)
  • creatine-phosphate biosynthesis
  • histamine biosynthesis
  • histamine degradation
  • thyroid hormone biosynthesis
  • thyroid hormone metabolism (via deiodination)
  • thyroid hormone metabolism (via conjugation and/or degradation)
  • selenocysteine biosynthesis II (archaea and eukaryotes)
  • tryptophan degradation XI (mammalian, via kynurenine)
  • serotonin degradation
  • phenylalanine degradation IV (mammalian, via side chain)
  • L-dopa degradation
  • noradrenaline and adrenaline degradation
  • purine degradation IV (aerobic)
  • alpha-tocopherol degradation
  • melatonin degradation I
  • glucuronate degradation
  • tryptophan degradation X (mammalian, via tryptamine)

    Release Notes for HumanCyc Version 12.0

    Released on April 1, 2008.

    The automated PathoLogic function to rescore pathways was run to clear out some obsolete pathways and get newly created pathways from MetaCyc. This was done with little human oversight -- just a quick visual pass to eliminate likely false positive pathways. 55 pathways were deleted from HumanCyc, and 116 new pathways (including superpathways) were imported from MetaCyc.

    Release Notes for HumanCyc Version 10.6

    Released on December 15, 2006.

    We have added two new human metabolic pathways and a superpathway in this release:

  • cholesterol biosynthesis II (via 24,25-dihydrolanosterol)
  • cholesterol biosynthesis III (via desmosterol)
  • superpathway of cholesterol biosynthesis

    The new pathways expand our coverage of cholesterol biosynthesis by illustrating other biosynthetic intermediates that have been shown to occur. The pre-existing pathway was renamed cholesterol biosynthesis I. The superpathway combines these three pathways, giving an overview of some of the multiple possible routes for cholesterol biosynthesis. Descriptive comments and references have been entered for these pathways and for the respective enzyme entries comprising these pathways.

    Release Notes for HumanCyc Version 10.5

    Released on September 8, 2006.

    We have added two new human metabolic pathways in this release:

  • anandamide degradation
  • dopamine degradation

    These pathways describe the degradation of anandamide, a member of the endocannabinoid class of signaling lipids, and the degradation of dopamine, a neurotransmitter and physiological regulator. Descriptive comments and references have been entered for these pathways and for the respective enzyme entries comprising these pathways.

    Release Notes for HumanCyc Version 9.1

    Released on May 23, 2005.

    We have added one new human metabolic pathway in this release:

  • cholesterol biosynthesis

    This pathway describes the biosynthesis of cholesterol from farnesyl diphosphate in a series of 22 reactions.  The biosynthesis of farnesyl diphosphate from acetyl-CoA is described in the linked mevalonate pathway in HumanCyc. The cholesterol pathway proceeds through the formation of lanosterol, followed by the series of membrane-associated reactions that lead to the formation of cholesterol. Extensive descriptive comments and references have been entered for this pathway and for the respective enzyme entries comprising this pathway.

    Release Notes for HumanCyc Version 9.0

    Released on February 25, 2005.

    We have added several new human metabolic pathways in this release:

  • catecholamine biosynthesis
  • nicotine degradation II
  • nicotine degradation III
  • bupropion degradation

    The catecholamine pathway describes the biosynthesis of the neurotransmitters dopamine, norepinephrine, and epinephrine. The metabolism of xenobiotics is described in the two linked pathways of nicotine degradation, and the pathway for the degradation of the antidepressant drug bupropion, which is also used in smoking cessation therapy. Extensive descriptive comments and references have been entered for these pathways and for the respective enzyme entries comprising these pathways.

    Release Notes for HumanCyc Version 8.0

    Released on March 12, 2004.

    We are continuing on-going curation of new and existing human metabolic pathways. In this release, three new pathways have been added:

  • oxidative ethanol degradation I
  • oxidative ethanol degradation II
  • oxidative ethanol degradation III

    Extensive descriptive comments and references have been entered for these pathways and for the respective gene, enzyme and reaction entries comprising these pathways. In describing the genes that encode the enzymes and/or subunits of enzymes catalyzing steps of pathways, specific emphasis has been placed on describing sites of genetic polymorphism and their associated genotypes and/or disease associations.

    Human pathways span multiple cellular and tissue compartments. The partitioning of these pathways across cellular and tissue compartments has also been described.

    Release Notes for HumanCyc Version 7.6

    Released on November 4, 2003.

    In this release, we have made putative functional assignments to 22 genes in HumanCyc. These functional assignments were made to fill pathway holes in the database. A pathway hole occurs when a reaction in a pathway does not have an assigned enzyme. The putative enzymes that fill these pathway holes were identified using a prediction program developed by Green and Karp and described in "A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases". Each enzymatic reaction linked to an enzyme by this program is identified by the evidence code "Computational Evidence: EV-COMP-HINF-FN-FROM-SEQ". The evidence code indicates the source of information as computationally-derived from sequence analysis with human review. The gene product field of the corresponding enzyme has also been updated to include the functional description of the reaction to which it has been linked.

  • ENSG00000068120-MONOMER / nucleotide binding protein / dephospho-CoA kinase
  • ENSG00000069535-MONOMER / amine oxidase (flavin-containing) B / putrescine oxidase
  • ENSG00000084754-MONOMER / trifunctional enzyme, alpha subunit, mitochondrial precursor / 3-hydroxybutyryl-CoA epimerase
  • ENSG00000087299-MONOMER / malate dehydrogenase (acceptor)
  • ENSG00000094841-MONOMER / uracil phosphoribosyltransferase
  • ENSG00000100412-MONOMER / aconitate hydratase, mitochondrial precursor
  • ENSG00000101156-MONOMER / uridine kinase-like 1 / uracil phosphoribosyltransferase
  • ENSG00000118498-MONOMER / DJ20N2.1 (fragment) / cytosine deaminase
  • ENSG00000120677-MONOMER / BA215B13.2 (fragment) / aspartate ammonia-lyase
  • ENSG00000127884-MONOMER / enoyl-CoA hydratase, mitochondrial precursor / 3-hydroxybutyryl-CoA dehydratase
  • ENSG00000135838-MONOMER / N-acetylneuraminate lyase / N-acetylneuraminate lyase
  • ENSG00000136877-MONOMER / folylpolyglutamate synthase, mitochondrial precursor / dihydrofolate synthase
  • ENSG00000139344-MONOMER / imidazolonepropionase
  • ENSG00000143149-MONOMER / aldehyde dehydrogenase, E3 isoenzyme / betaine-aldehyde dehydrogenase
  • ENSG00000143891-MONOMER / aldose 1-epimerase
  • ENSG00000148459-MONOMER / trans-prenyltransferase
  • ENSG00000152642-MONOMER / glycerol-3-phosphate dehydrogenase (NAD+), cytoplasmic / glycerol-3-phosphate dehydrogenase (NAD(P)+)
  • ENSG00000162066-MONOMER / CGI-14 protein / N-acetylglucosamine-6-phosphate deacetylase
  • ENSG00000163864-MONOMER / nicotinate-nucleotide adenylyltransferase
  • ENSG00000167588-MONOMER / glycerol-3-phosphate dehydrogenase (NAD+), cytoplasmic / glycerol-3-phosphate dehydrogenase (NAD(P)+)
  • ENSG00000169710-MONOMER / fatty acid synthase
  • ENSG00000172992-MONOMER / nucleotide binding protein / dephospho-CoA kinase