Evolutionary constraints permeate large metabolic networks

Table 1 The 15 most highly constrained sets of metabolic reactions.

P_min	Reactions	Pathways/Function	KEGG Identifier
22.73	3	Histidine degradation	K01468 K01712 K01745
21.93	2	Unknown/methyltransferase	K06346 K06960
21.56	2	Transmembrane sensor/Copper resistance	K07156 K07245
21.45	2	Glycosyltransferase/Glucan biosynthesis	K03669 K03670
21.22	2	Glutamate metabolism	K00620 K00642
18.04	3	Pyrroloquinoline quinone (PQQ) biosynthesis	K06139 K06136 K06138
17.58	4	Cobalamin biosynthesis	K02232 K02227 K02233 K02231
17.51	2	Glutamate-ammonia-ligase adenylyltransferase/uridylyltransferase	K00982 K00990
17.17	2	Biotin biosynthesis	K00652 K01935
17.06	2	Acetyl CoA, fatty acid and amino acid metabolism	K00022 K01692
17.01	4	Inositol phosphate catabolism	K03335 K03336 K03337 K03338
16.84	2	Starch and glycogen biosynthesis	K00700 K00975
16.77	2	4-hydroxy 3-oxovalerate aldolase/acetaldehyde dehydrogenase	K01666 K04073
16.69	2	Butanoate Metabolism	K00023 K03821

Column 1 from the left shows the negative decadic logarithm of the lowest P-value for a reaction pair within a constrained reaction set. That is, for constrained reaction sets comprising more than two reactions, all reaction pairs have a P-value lower than that indicated in this column by the Table. Column 2 shows the number of reactions in each set. Column 3 shows, for reaction sets with a known pathway annotation, the respective biochemical pathway [36], or, where the pathway is not known or ambiguous, the functions of the enzymes, separated by a slash. Column 4 shows the unique KEGG identifiers [36] for the respective enzyme-coding genes.

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