Scopes of Compounds
2.1 Scopes of single compounds
In the following, the concept of scopes has been applied to the metabolic network retrieved from the KEGG database (cf. Appendix A.2). In partic-ular the single scopes of 4104 compounds have been calculated. Due to it’s ubiquity, water is assumed to be present for all calculations in this work, unless otherwise stated. Methodically this means, that water is added to all seeds. Despite of the fact that there are 2 compounds in each seed, these scopes will still be termed as single scopes. Using the available reactions, water itself can be transformed into 4 other metabolites, namely O2, H2O2, H+ and O−2. All scopes therefore contain at least these 5 metabolites.
Figure 2.1 shows the distribution of the scope sizes. The sizes range from 5 to 2183 compounds. The distribution is found to be very non-uniform.
While most of the scopes are rather small, there also exist a few large scopes.
Furthermore, for sizes larger than 32 the distribution contains gaps, which may become very wide between larger scopes. There exists only a small number of very large scopes, in particular with the sizes 1554, 1556, 1558, 1560, 1596 and 2183. The next smaller scope has only a size of 560.
As expected, some of the compounds result in the same scope (cf. equa-tion 1.18) which can be seen as large peaks in the distribuequa-tion. In fact, there exist only 2923 distinct scopes. To demonstrate the effect on the distribu-tion, figure 2.2 shows the scope sizes of the distinct scopes only. It can be seen that for small scopes typically several distinct scopes with the same sizes exist whereas for larger scopes the large number at a certain size in figure 2.1 is mainly determined by interconvertible seed compounds.
Table 2.1 lists the largest single scopes sorted by size. The largest scope of size 2183 results from four different single compound seeds which are
21
1 10 100 1000 scope size (σ) 1
10 100 1000
occurence (number of seeds)
Figure 2.1: Size distribution of the scopes of 4104 single com-pounds.
1 10 100 1000
scope size (σ) 1
10 100 1000
occurence (number of scopes)
Figure 2.2: Size distribution of the 2923 distinct scopes.
adenosine 5’-phosphosulfate (APS), 3’-phosphoadenosine 5’-phosphosulfate (PAPS), dephospho-CoA, and UDP-6-sulfoquinovose. APS and PAPS play an important role in the sulfur metabolism in many microorganisms. Dephospho-CoA is a direct precursor in the Dephospho-CoA biosynthesis pathway. UDP-6-sulfoquinovose plays a role in the glycerolipid metabolism.
Of particular interest is also the scope of size 1554 which can be reached from 97 different single seed compounds. Among them are central cofactors such as ATP, UTP, CTP and GTP as well as the corresponding mono- and diphosphates and the nicotinamide dinucleotides NADH and NADPH.
Many scopes are subsets of larger scopes (see equation 1.17). For example, the scope of ATP is a subset of the scope of APS. From this it follows that ATP can be synthesized from APS. The opposite process is not possible which simply follows from the fact that APS is composed of adenine, ribose, sulfate and phosphate, whereas the adenosine phosphates AMP, ADP, and ATP contain the same building blocks except sulfate.
2.2 Interconvertibilities
As shown, many biochemical compounds are interconvertible as described by equation 1.18. Obviously, it is necessary for two interconvertible compounds that they are composed of the same chemical elements. However, not all compounds fulfilling this condition are interconvertible. This is the case if the reactions present in the network do not have the capability to perform the interconversion. As an example, we consider the two compounds coenzyme A and dephospho-CoA. Both substances consist of the same chemical elements.
The only difference is that coenzyme A contains three phosphate groups
KEGG ID compound name scope size
C00053 3’-Phosphoadenylyl sulfate 2183
C00224 Adenylylsulfate 2183
C00882 Dephospho-CoA 2183
C11521 UDP-6-sulfoquinovose 2183
C00016 FAD 1596
C04652 UDP-2,3-bis(3-hydroxytetradecanoyl)glucosamine 1560
C06435 5’-Butyrylphosphoinosine 1558
C05227 UDP-sugar 1556
C01299 Adenylyl-[L-glutamate:ammonia ligase (ADP-forming)] 1556
C00002 ATP 1554
C00003 NAD 1554
C03483 Adenosine 5’-tetraphosphate 1554
... ... ...
Table 2.1: List of single compound seeds and their scope sizes ordered by decreasing size (abbreviated). Corresponds to the largest scopes shown in figure 2.1
whereas dephospho-CoA contains only two. Our calculations revealed that coenzyme A is in the scope of dephospho-CoA, whereas the opposite is not true. Even though the network includes the reaction
dephospho-CoA + ATP*)CoA + ADP, (2.1) it does not represent a direct interconversion between the two compounds since it requires the presence of ATP or ADP. However, coenzyme A can be produced from dephospho-CoA in a higher number of steps. This is possible since ATP is in the scope of dephospho-CoA (see above). In contrast, dephospho-CoA cannot be produced from coenzyme A since its scope does not contain ADP.
In order to get an impression of how many of the compounds containing the same elements are really interconvertible, we have analyzed all pairs of compounds containing only the elements C, H, and O. The database contains 1501 such compounds forming 1125750 different pairs. From these pairs of compounds, only 6126 pairs (0.54%) represent two compounds which can be interconverted. Analogously, we have analyzed all 186 compounds containing the elements C, H, O, N, P, and S. It turns out that 1.24% of all pairs of these compounds are interconvertible. Interestingly, for all 363 compounds containing the elements C, H, O, N, and P, over 7% of all pairs are inter-convertible. This high percentage can be explained by the fact that many
of those compounds are seed compounds of the scope of ATP. Table A.1 in section A.5 summarizes the results for all existing element combinations.