Reaction participants
Content:
- How are participants represented?
- What types of participants exist?
- Searching by participant
- Related documents
How are participants represented?
Rhea uses the chemical dictionary ChEBI (Chemical Entities of Biological Interest) to describe the chemical compounds that participate in Rhea reactions in a computationally tractable manner.
The ChEBI ontology handles all forms of a given chemical compound (e.g. neutral, protonated, zwitterionic, tautomeric, isotopic). Each form is assigned its own unique ChEBI identifier and related forms are linked by relationships. To provide non-redundant and chemically balanced reactions, Rhea uses those ChEBI entities that describe the form that is the major microspecies at pH 7.3
ChEBI assigns a unique name to each entity, the ChEBI common name, and collects optional synomyms from various sources. Rhea assigns and uses a name that may differ from the ChEBI common name to the ChEBI entities that are used in Rhea, and this name is stored as a synomym (with UniProt as the source) in ChEBI (e.g. CHEBI:57416 is named D-alanine zwitterion by ChEBI and D-alanine by Rhea).
ChEBI provides structure information for its entities that is used to build and search Rhea:
- formula and charge
These are used to ensure that Rhea reactions are balanced with respect to mass and charge.
- InChIKey and SMILES
These are string representations of chemical structures than can be used in the advanced text search and structure search.
- 2D structure coordinates (MDL Molfile)
Information about the Rhea reaction participants can be downloaded from our FTP site.
What types of participants exist?
Rhea reactions may contain the following three types of reaction participants:
Small molecule
We use the term small molecule to refer to a participant, or class of participants, of low molecular weight (MW) that we can identify by a ChEBI identifier. Its structure may be fully defined (e.g. ethanol, L-alanine, cholesterol, etc.) or contain an undefined part that is represented as an R group (e.g. an alcohol, a primary alcohol, a sphingolipid, etc.).
By default, the Rhea search exploits the hierarchical classification of the ChEBI ontology. In other words, if you search for a compound class like CHEBI:59871 (a D-alpha-amino acid), you will retrieve reactions involving CHEBI:59871 but also reactions involving more specific compounds (D-alanine, D-glutamate, etc). You can also perform an exact search to retrieve only reactions involving CHEBI:59871 (see Advanced text search for details).
Please note that most chemoinformatics tools work only with fully defined structures and this impacts our structure search.
Example: alanine
Macromolecule
We use the term macromolecule to refer to proteins and nucleic acids. Rhea represents a macromolecule with the ChEBI entities that describe the reactive parts that are involved in the reaction (e.g. a modified amino-acid or nucleotide) and uses a text label for the unmodified part. Since different macromolecules may contain the same reactive part, Rhea assigns unique identifiers, with a RHEA-COMP prefix, to each Rhea macromolecule.
Protein
Reactions that involve proteins comprise post-translational modifications (PTMs) on an amino acid side chain or at a protein's N- or C-terminus, as well as carrier proteins (e.g. Acyl Carrier Protein (ACP)) and proteins that act as electron donor/acceptor (e.g. NADPH--hemoprotein reductase).
Rhea follows the NC-IUBMB style of labeling proteins, where the name of the protein is surrounded by square brackets. Examples:
| Participant name | Participant identifier | Reactive part name | Reactive part identifier |
|---|---|---|---|
| L-lysyl-[protein] | RHEA-COMP:9752 | L-lysine residue | CHEBI:29969 |
| [protein]-C-terminal-L-glutamine | RHEA-COMP:14703 | C-terminal L-glutaminyl residue | CHEBI:88115 |
| apo-[ACP] | RHEA-COMP:9620 | L-seryl residue | CHEBI:29999 |
| holo-[ACP] | RHEA-COMP:9685 | O-(pantetheine-4ʼ-phosphoryl)-L-serine residue | CHEBI:64479 |
| holo-[peptidyl-carrier protein] | RHEA-COMP:11480 | O-(pantetheine-4ʼ-phosphoryl)-L-serine residue | CHEBI:64479 |
| reduced [NADPH--hemoprotein reductase] | RHEA-COMP:11964 | FMNH2 | CHEBI:57618 |
| oxidized [NADPH--hemoprotein reductase] | RHEA-COMP:11965 | FMN | CHEBI:58210 |
Examples: L-lysine methylation, reactions involving acyl carrier protein ([ACP])
Nucleic acid
Modification of nucleic acids:
- DNA
- RNA
- mRNA
- rRNA
- snRNA
- tRNA
- ...
Example: RNA methylation
Polymer
We use the term polymer to refer to a compound that consists of a constant part and a number of repeated units. The number of repetitions is known as the polymerization index (PI). ChEBI describes polmers with an undefined PI. To ensure that a (de)polymerization reaction is balanced at the level of mass and charge, Rhea must define two polymers that differ by one unit by using different abstract PIs for the same underlying ChEBI polymer and assign unique identifiers, with a RHEA-COMP prefix, to each Rhea polymer.
In a polymerization reaction, the abstract PI changes from (n) to (n+1), whereas in a depolymerization reaction, it changes from (n) to (n-1). The following figure shows two Rhea polymers that have the same underlying ChEBI polymer but different abstract PIs:
The formula and the charge of a polymer are computed based on the constant part and the repeated unit:
| RHEA-COMP:13258 | Constant part | Repeated unit |
|---|---|---|
| Formula= C15H15N6O3(C5H6NO3)n+1 | C15H15N6O3 | (C5H6NO3)n+1 |
| Charge= (-1)(-1)n+1 | -1 | (-1)n+1 |
A polymer can be modified at its constant part or at its repeated unit part (see reactions involving polymers).
Example: Ubiquinone
Ubiquinones are a group of lipid-soluble benzoquinones involved in electron transport. Their structures have a side chain of variable length which consists of one to twelve mono-unsaturated trans-isoprenoids units.
When the length of the isoprenoids side chain is unknown, we represent the class of ubiquinone by the Rhea polymer RHEA-COMP:9565, using the underlying ChEBI polymer CHEBI:16389.
CHEBI:16389 entry is a specific form (instance) of CHEBI:132124 which represents a quinone.
The human ubiquinone has a side chain of 10 trans-isoprenoids units, it is also called ubiquinone-10, CoQ10, Co-Q10, ubiquinone Q10. CHEBI:46245 (ubiquinone-10) as a fully defined structure, it is then considered as a small molecule and not as a polymer.
Thanks to the ChEBI relationship, CHEBI:46245 is a CHEBI:16389, if you search for CHEBI:16389 you will retrieve the reactions involving Rhea polymers with CHEBI:16389 as underlying ChEBI polymer as well as the reactions involving descendants of CHEBI:16389, like CHEBI:46245 (ubiquinone-10), CHEBI:61683 (ubiquinone-8), etc.
Similarly if you search Rhea for CHEBI:132124 (a quinone), you will retrieve ubiquinone data-related but also data for other quinones like menaquinones.
Searching by participant
Summary of the search functionalities by type of participant.
| Reaction participant | Search by name | Search by identifier | Search by InChIKey | Structure search | Example |
|---|---|---|---|---|---|
| Small molecule (fully defined) | yes | ChEBI ID | yes | yes | alanine (CHEBI:66916) |
| Small molecule (partially defined) | yes | ChEBI ID | no | yes | a D-alpha-amino acid (CHEBI:59871) as a class |
| a D-alpha-amino acid (CHEBI:59871) as an exact search | |||||
| Macromolecule | yes | RHEA-COMP or ChEBI ID | no | yes | holo-[ACP] (RHEA-COMP:9685) Reactive part (CHEBI:64479) |
| Polymer | yes | RHEA-COMP or ChEBI ID | no | no | (RHEA-COMP:13258) Underlying ChEBI polymer (CHEBI:136572) |