How to make use of the KEGG metabolic database
How do I find a standard metabolic pathway ?
From the KEGG table
of contents click on the link 'Metabolic
pathways' under pathway category. A list with all pathways will
be available. To find the pathway link for 'Lysine biosynthesis',
scroll down on the browser to the group of pathways called 'amino
acid metabolism' and click on the link. You should now see the standard
for lysine biosynthesis.
How do I find species specific pathway maps ?
Once in the standard pathway map, select the species name (e.g.
coli) in the 'Go To' window and click on Exec button.
You should now see the same pathway, but indicating the species
name in the window (e.g. Escherichia coli). All known E.coli enzymes
for which a database entry exists are labeled in green. The example
indicates that not all enzymes are colored. This indicates that
the corresponding enzyme (pathway) does not exist in this organism
or that no information is found in any of the public databases (Swiss
Prot, GenBank, Protein Data Base etc...). Since the complete
genome for E.coli has been sequenced this very likely indicate
that a pathway does not exist in this Gram-negative bacteria. However,
about 39% of all predicted genes (called ORFs or open reading frames)
are not associated with any known protein, biochemical or physiological
activity and not all pathways are therefor known and not described
in KEGG. Some organisms such as mouse and human are not listed for
lysine biosynthesis but show a map for glutamate,
for example. L-lysine, unlike glutamate, is an essential amino
acid for both human and mouse. L-lysine has to be part of our diet,
because we lack the necessary enzymes for its biosynthesis!!!
How do I find a chemical structure, metabolite information from
a pathway map ?
Note that the immediate precursor of L-lysine also serves as a substrate
for peptidoglycan synthesis to form the activated polypeptide
the structure of which can be found by clicking on the small circle
next to the compound name. You will see an information page for
KEGG entry C04882.
The preceding problem gives an example of how to find information
about a metabolite, namely its chemical structure, formula, KEGG
entry number, and pathway map numbers for which it is an intermediate.
Clicking on a substrate name (or its circle) on a pathway map page
is the easiest way to find relevant chemical information about a
substrate and its shared pathways. The same can be done for an enzyme
by clicking on the E.C. number box or for an intersecting pathway
indicated in a roundish shaped box. For example a link exists from
the lysine biosynthesis map to the 'lysine degradation' pathway
map. Clicking on the box marked 'Lysine
degradation' will bring us to the corresponding catabolic processes.
Note that the species selection will not change (we last selected
E.coli pathways above). The new pathway map number is MAP00310.
How do I find a chemical structure, metabolite information by
keyword search ?
To find a pathway metabolite or enzyme, the table of contents offers
a direct link to the DBGET Ligand database at KEGG. This search
mode can be found at the 'table of contents' page under the 'enzyme'
category, DBGET search. Click on the link called 'Ligand'
to access a generic search mode that allows a keyword entry. Note
that an exact enzyme number or compound number is not necessary
in the DBGET database. To find information about lysine or L-lysine,
type in 'lysine' and hit the return (enter) key. You will receive
a return list with 159
hits. the search returned all KEGG entries that contained the
word 'lysine' anywhere in the enzyme or compound name. The list
contains 45 enzyme links (ec: x.x.x.xx) and 51 compound links (cpd:
Cxxxxx), one being L-lysine (cpd:C00047)
and all others derivatives thereof. Clicking on the cpd number will
bring you to the chemical structure information sheet. This sheet
lists compound entry number for L-lysine (note that D-lysine has
a different entry, of course), common name(s), formula, structure,
all pathway maps that contain L-lysine as metabolite (5 maps for
L-lysine including synthesis and degradation, biotin metabolism,
alkaloid biosynthesis II, and Aminoacyl-tRNA biosynthesis), and
finally a list of all known enzymes that use L-lysine as a substrate.
General information on biological molecules
One additional feature that is very helpful to use are the molecular
catalogue entries, specifically the 'compound
classification'. This link leads to a catalogue of metabolites
classified according to their functional class, e.g., carbohydrates,
fatty acids, phospholipids, neurotransmitters etc.. If you want
to look up the structures of a class of molecules like the amino
acids or various hexoses, this link will give you the best and broadest
result to quickly find what you need. Use this link as a reference
for structure information. As an example we are interested in the
general structure of steroid
link provided in the category 'Lipids' provides a page containing
the names and chemical structures of seven cholesterol derived steroid
hormones. Clicking on the name link 'aldosterone'
connects to a structure information page providing a link to the
pathway map for C21 steroid hormone metabolism (MAP00140).
Following the pathway map link results in the standard pathway for
steroid hormone metabolism with aldosterone position marked as a
red circle (because we started our search from aldosterone). Selecting
sapiens version of the map shows as a variety of pathways whereas
no corresponding bacterial
map for E.coli exists. Not surprisingly, because microorganisms
lack the capability of synthesizing steroid hormones. The database
offers only links to eukaryotic organisms.
Why are some enzymes not colored even though they are part of
a pathway of enzymes that are colored?
Sometimes an enzyme is not marked where you would expect it like
in the aldosterone pathway above. This pathway map shows all known
reactions summarized in a standard pathway map. Species specific
enzymes are marked green. Missing enzymes that appear to interrupt
a pathway occur when no entry for this enzyme (gene, amino acid
sequence, protein structure) exists in any database, not
only KEGG. The enzyme with the entry EC
18.104.22.168 is Corticosterone 18-monooxygenase and converts
corticosterone into aldosterone. Following the E.C. link for this
enzyme to the entry in GenBank
(mirrored from NCBI) shows one nucleic acid sequence report for
rat (exon 9 of Rat CYP11B2 gene for aldosterone synthase). A human
homologue is likely to exist for this monooxygenase, but no sequence
has been reported yet.
o m e
Copyright © 2000-2003
Lukas K. Buehler