Metabolic Networks

Metabolic networks have four columns. The first declares a unique name for the enzyme or enzymatic complex; the second declares a unique name for the reaction; the third column lists using comma unique names for substrates; and the last row list using comma unique names for products. To declare metabolites located at the periplasm or extracellular compartments, the user should employ the prefix “PER-” and “EX-”, respectively. Use spontaneous for non-enzymatic reactions.

Examples:

GENE    REACTION        SUBSTRATES      PRODUCTS
spontaneous     LACTOSE-MUTAROTATION    alpha-lactose   beta-lactose
spontaneous     GALACTOSE-MUTAROTATION  alpha-GALACTOSE beta-GALACTOSE
spontaneous     GLUCOSE-MUTAROTATION    alpha-glucose   beta-glucose
LACY-MONOMER    TRANS-RXN-24    PER-PROTON, PER-alpha-lactose   PROTON, alpha-lactose
LACY-MONOMER    TRANS-RXN-24-beta       PER-PROTON, PER-beta-lactose    PROTON, beta-lactose
LACY-MONOMER    TRANS-RXN-94    PER-PROTON, PER-MELIBIOSE       PROTON, MELIBIOSE
LACY-MONOMER    RXN0-7215       PER-PROTON, PER-CPD-3561        PROTON, CPD-3561
LACY-MONOMER    RXN0-7217       PER-PROTON, PER-CPD-3785        PROTON, CPD-3785
LACY-MONOMER    RXN-17755       PER-PROTON, PER-CPD-3801        PROTON, CPD-3801
BETAGALACTOSID-CPLX     BETAGALACTOSID-RXN      beta-lactose, WATER     beta-GALACTOSE, beta-glucose
BETAGALACTOSID-CPLX     BETAGALACTOSID-RXN-alpha        alpha-lactose, WATER    alpha-GALACTOSE, alpha-glucose
BETAGALACTOSID-CPLX     RXN0-5363       alpha-lactose   alpha-ALLOLACTOSE
BETAGALACTOSID-CPLX     RXN0-5363-beta  beta-lactose    beta-ALLOLACTOSE
BETAGALACTOSID-CPLX     ALLOLACTOSE-DEG-alpha   alpha-ALLOLACTOSE       alpha-GALACTOSE, alpha-glucose
BETAGALACTOSID-CPLX     ALLOLACTOSE-DEG-beta    beta-ALLOLACTOSE        beta-GALACTOSE, beta-glucose
BETAGALACTOSID-CPLX     RXN-17726       CPD-3561, WATER beta-GALACTOSE, Fructofuranose
BETAGALACTOSID-CPLX     RXN0-7219       CPD-3785, WATER beta-GALACTOSE, D-ARABINOSE
GALACTOACETYLTRAN-CPLX  GALACTOACETYLTRAN-RXN-galactose beta-GALACTOSE, ACETYL-COA      6-Acetyl-beta-D-Galactose, CO-A

OR

GENE    REACTION        SUBSTRATES      PRODUCTS
spontaneous     LACTOSE-MUTAROTATION    alpha-lactose   beta-lactose
spontaneous     GALACTOSE-MUTAROTATION  alpha-GALACTOSE beta-GALACTOSE
spontaneous     GLUCOSE-MUTAROTATION    alpha-glucose   beta-glucose
lacY    TRANS-RXN-24    PER-PROTON, PER-alpha-lactose   PROTON, alpha-lactose
lacY    TRANS-RXN-24-beta       PER-PROTON, PER-beta-lactose    PROTON, beta-lactose
lacY    TRANS-RXN-94    PER-PROTON, PER-MELIBIOSE       PROTON, MELIBIOSE
lacY    RXN0-7215       PER-PROTON, PER-CPD-3561        PROTON, CPD-3561
lacY    RXN0-7217       PER-PROTON, PER-CPD-3785        PROTON, CPD-3785
lacY    RXN-17755       PER-PROTON, PER-CPD-3801        PROTON, CPD-3801
[lacZ,lacZ,lacZ,lacZ]   BETAGALACTOSID-RXN      beta-lactose, WATER     beta-GALACTOSE, beta-glucose
[lacZ,lacZ,lacZ,lacZ]   BETAGALACTOSID-RXN-alpha        alpha-lactose, WATER    alpha-GALACTOSE, alpha-glucose
[lacZ,lacZ,lacZ,lacZ]   RXN0-5363       alpha-lactose   alpha-ALLOLACTOSE
[lacZ,lacZ,lacZ,lacZ]   RXN0-5363-beta  beta-lactose    beta-ALLOLACTOSE
[lacZ,lacZ,lacZ,lacZ]   ALLOLACTOSE-DEG-alpha   alpha-ALLOLACTOSE, WATER        alpha-GALACTOSE, alpha-glucose
[lacZ,lacZ,lacZ,lacZ]   ALLOLACTOSE-DEG-beta    beta-ALLOLACTOSE, WATER beta-GALACTOSE, beta-glucose
[lacZ,lacZ,lacZ,lacZ]   RXN-17726       CPD-3561, WATER beta-GALACTOSE, Fructofuranose
[lacZ,lacZ,lacZ,lacZ]   RXN0-7219       CPD-3785, WATER beta-GALACTOSE, D-ARABINOSE
[lacA,lacA,lacA]        GALACTOACETYLTRAN-RXN-galactose beta-GALACTOSE, ACETYL-COA      6-Acetyl-beta-D-Galactose, CO-A

OR

GENE    REACTION        SUBSTRATES      PRODUCTS
spontaneous     LACTOSE-MUTAROTATION    alpha-lactose   beta-lactose
spontaneous     GALACTOSE-MUTAROTATION  alpha-GALACTOSE beta-GALACTOSE
spontaneous     GLUCOSE-MUTAROTATION    alpha-glucose   beta-glucose
lacY    TRANS-RXN-24    PER-PROTON, PER-alpha-lactose   PROTON, alpha-lactose
lacY    TRANS-RXN-24-beta       PER-PROTON, PER-beta-lactose    PROTON, beta-lactose
lacY    TRANS-RXN-94    PER-PROTON, PER-MELIBIOSE       PROTON, MELIBIOSE
lacY    RXN0-7215       PER-PROTON, PER-CPD-3561        PROTON, CPD-3561
lacY    RXN0-7217       PER-PROTON, PER-CPD-3785        PROTON, CPD-3785
lacY    RXN-17755       PER-PROTON, PER-CPD-3801        PROTON, CPD-3801
lacZ    BETAGALACTOSID-RXN      beta-lactose, WATER     beta-GALACTOSE, beta-glucose
lacZ    BETAGALACTOSID-RXN-alpha        alpha-lactose, WATER    alpha-GALACTOSE, alpha-glucose
lacZ    RXN0-5363       alpha-lactose   alpha-ALLOLACTOSE
lacZ    RXN0-5363-beta  beta-lactose    beta-ALLOLACTOSE
lacZ    ALLOLACTOSE-DEG-alpha   alpha-ALLOLACTOSE, WATER        alpha-GALACTOSE, alpha-glucose
lacZ    ALLOLACTOSE-DEG-beta    beta-ALLOLACTOSE, WATER beta-GALACTOSE, beta-glucose
lacZ    RXN-17726       CPD-3561, WATER beta-GALACTOSE, Fructofuranose
lacZ    RXN0-7219       CPD-3785, WATER beta-GALACTOSE, D-ARABINOSE
lacA    GALACTOACETYLTRAN-RXN-galactose beta-GALACTOSE, ACETYL-COA      6-Acetyl-beta-D-Galactose, CO-A

Note

Visualization in Cytoscape. Transform the four-columns file into a two-columns file with the helper script “Expand metabolic network.ipynb”, paste the results in a new file, and import the network into Cytoscape. Colors and arrows remains to the user for customization.

_images/Fig_Lactose_MetNetwork.png

Finally, execute the “Rules from metabolic network.ipynb” to obtain the Rules to model the defined metabolic network. The complete rule-based model can be found in the lactose folder from the Network Biology Lab GitHub repository here.

Rule('LACTOSE_MUTAROTATION',
        met(name = 'alpha_lactose', loc = 'cyt') |
        met(name = 'beta_lactose', loc = 'cyt'),
        Parameter('fwd_LACTOSE_MUTAROTATION', 1),
        Parameter('rvs_LACTOSE_MUTAROTATION', 1))

Rule('GALACTOSE_MUTAROTATION',
        met(name = 'alpha_GALACTOSE', loc = 'cyt') |
        met(name = 'beta_GALACTOSE', loc = 'cyt'),
        Parameter('fwd_GALACTOSE_MUTAROTATION', 1),
        Parameter('rvs_GALACTOSE_MUTAROTATION', 1))

Rule('GLUCOSE_MUTAROTATION',
        met(name = 'alpha_glucose', loc = 'cyt') |
        met(name = 'beta_glucose', loc = 'cyt'),
        Parameter('fwd_GLUCOSE_MUTAROTATION', 1),
        Parameter('rvs_GLUCOSE_MUTAROTATION', 1))

Rule('TRANS_RXN_24',
        prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'per') +
        met(name = 'alpha_lactose', loc = 'per') |
        prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'cyt') +
        met(name = 'alpha_lactose', loc = 'cyt'),
        Parameter('fwd_TRANS_RXN_24', 1),
        Parameter('rvs_TRANS_RXN_24', 1))

Rule('TRANS_RXN_24_beta',
        prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'per') +
        met(name = 'beta_lactose', loc = 'per') |
        prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'cyt') +
        met(name = 'beta_lactose', loc = 'cyt'),
        Parameter('fwd_TRANS_RXN_24_beta', 1),
        Parameter('rvs_TRANS_RXN_24_beta', 1))

Rule('TRANS_RXN_94',
        prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'per') +
        met(name = 'MELIBIOSE', loc = 'per') |
        prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'cyt') +
        met(name = 'MELIBIOSE', loc = 'cyt'),
        Parameter('fwd_TRANS_RXN_94', 1),
        Parameter('rvs_TRANS_RXN_94', 1))

Rule('RXN0_7215', prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'per') +
        met(name = 'CPD_3561', loc = 'per') |
        prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'cyt') +
        met(name = 'CPD_3561', loc = 'cyt'),
        Parameter('fwd_RXN0_7215', 1),
        Parameter('rvs_RXN0_7215', 1))

Rule('RXN0_7217', prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'per') +
        met(name = 'CPD_3785', loc = 'per') |
        prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'cyt') +
        met(name = 'CPD_3785', loc = 'cyt'),
        Parameter('fwd_RXN0_7217', 1),
        Parameter('rvs_RXN0_7217', 1))

Rule('RXN_17755', prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'per') +
        met(name = 'CPD_3801', loc = 'per') |
        prot(name = 'LACY_MONOMER') +
        met(name = 'PROTON', loc = 'cyt') +
        met(name = 'CPD_3801', loc = 'cyt'),
        Parameter('fwd_RXN_17755', 1),
        Parameter('rvs_RXN_17755', 1))

Rule('BETAGALACTOSID_RXN',
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'beta_lactose', loc = 'cyt') +
        met(name = 'WATER', loc = 'cyt') |
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'beta_GALACTOSE', loc = 'cyt') +
        met(name = 'beta_glucose', loc = 'cyt'),
        Parameter('fwd_BETAGALACTOSID_RXN', 1),
        Parameter('rvs_BETAGALACTOSID_RXN', 1))

Rule('BETAGALACTOSID_RXN_alpha',
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'alpha_lactose', loc = 'cyt') +
        met(name = 'WATER', loc = 'cyt') |
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'alpha_GALACTOSE', loc = 'cyt') +
        met(name = 'alpha_glucose', loc = 'cyt'),
        Parameter('fwd_BETAGALACTOSID_RXN_alpha', 1),
        Parameter('rvs_BETAGALACTOSID_RXN_alpha', 1))

Rule('RXN0_5363',
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'alpha_lactose', loc = 'cyt') |
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'alpha_ALLOLACTOSE', loc = 'cyt'),
        Parameter('fwd_RXN0_5363', 1),
        Parameter('rvs_RXN0_5363', 1))

Rule('RXN0_5363_beta',
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'beta_lactose', loc = 'cyt') |
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'beta_ALLOLACTOSE', loc = 'cyt'),
        Parameter('fwd_RXN0_5363_beta', 1),
        Parameter('rvs_RXN0_5363_beta', 1))

Rule('ALLOLACTOSE_DEG_alpha',
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'alpha_ALLOLACTOSE', loc = 'cyt') |
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'alpha_GALACTOSE', loc = 'cyt'),
        Parameter('fwd_ALLOLACTOSE_DEG_alpha', 1),
        Parameter('rvs_ALLOLACTOSE_DEG_alpha', 1))

Rule('ALLOLACTOSE_DEG_beta',
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'beta_ALLOLACTOSE', loc = 'cyt') |
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'beta_GALACTOSE', loc = 'cyt'),
        Parameter('fwd_ALLOLACTOSE_DEG_beta', 1),
        Parameter('rvs_ALLOLACTOSE_DEG_beta', 1))

Rule('RXN_17726',
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'CPD_3561', loc = 'cyt') +
        met(name = 'WATER', loc = 'cyt') |
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'beta_GALACTOSE', loc = 'cyt') +
        met(name = 'Fructofuranose', loc = 'cyt'),
        Parameter('fwd_RXN_17726', 1),
        Parameter('rvs_RXN_17726', 1))

Rule('RXN0_7219',
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'CPD_3785', loc = 'cyt') +
        met(name = 'WATER', loc = 'cyt') |
        cplx(name = 'BETAGALACTOSID_CPLX') +
        met(name = 'beta_GALACTOSE', loc = 'cyt') +
        met(name = 'D_ARABINOSE', loc = 'cyt'),
        Parameter('fwd_RXN0_7219', 1),
        Parameter('rvs_RXN0_7219', 1))

Rule('GALACTOACETYLTRAN_RXN_galactose',
        cplx(name = 'GALACTOACETYLTRAN_CPLX') +
        met(name = 'beta_GALACTOSE', loc = 'cyt') +
        met(name = 'ACETYL_COA', loc = 'cyt') |
        cplx(name = 'GALACTOACETYLTRAN_CPLX') +
        met(name = '_6_Acetyl_beta_D_Galactose', loc = 'cyt') +
        met(name = 'CO_A', loc = 'cyt'),
        Parameter('fwd_GALACTOACETYLTRAN_RXN_galactose', 1),
        Parameter('rvs_GALACTOACETYLTRAN_RXN_galactose', 1))

Note

Reversibility of Rules. Atlas writes reversible Rules for each reaction declared in the network file. The Parameter('rvs_RuleName', 1)) must be set to zero to define an irreversible reaction.

Note

Uniqueness of Rule names. Atlas will write Rules for unique metabolic reactions. Identical names will be reported for further curation.

Note

Simulation. The model can be simulated only with the instantiation of Monomers and Initials (More here). Run Monomer+Initials+Observables from metabolic network.ipynb to obtain automatically the necessary Monomers and Initials (including proteins and enzymatic complexes).

Plotting. The model can be observed only with the instantation of Observables (More here). Run Monomer+Initials+Observables from metabolic network.ipynb to obtain automatically the all possible Observables for metabolites.