Update of the LIPID MAPS comprehensive classification system for lipids

Abstract

In 2005, the International Lipid Classification and Nomenclature Committee under the sponsorship of the LIPID MAPS Consortium developed and established a "Comprehensive Classification System for Lipids" based on well-defined chemical and biochemical principles and using an ontology that is extensible, flexible, and scalable. This classification system, which is compatible with contemporary databasing and informatics needs, has now been accepted internationally and widely adopted. In response to considerable attention and requests from lipid researchers from around the globe and in a variety of fields, the comprehensive classification system has undergone significant revisions over the last few years to more fully represent lipid structures from a wider variety of sources and to provide additional levels of detail as necessary. The details of this classification system are reviewed and updated and are presented here, along with revisions to its suggested nomenclature and structure-drawing recommendations for lipids.

Full text

Update of the LIPID MAPS comprehensive classification
system for lipids
1
Eoin Fahy,*Shankar Subramaniam,
†
Robert C. Murphy,
§
Masahiro Nishijima,**
Christian R. H. Raetz,
††
Takao Shimizu,
§§
Friedrich Spener,*** Gerrit van Meer,
†††
Michael J. O. Wakelam,
§§§
and Edward A. Dennis
2,
****
San Diego Supercomputer Center,* Department of Bioengineering,
†
and Department of Chemistry and
Biochemistry and Department of Pharmacology of the School of Medicine,**** University of California,
San Diego, La Jolla, CA 92093-0505; Department of Pharmacology,
§
University of Colorado Denver, Aurora,
CO 80045-0598; National Institute of Health Sciences,** Setagaya-ku, Tokyo 158-8501, Japan; Department
of Biochemistry,
††
Duke University Medical Center, Durham, NC 27710; Department of Biochemistry
and Molecular Biology,
§§
Faculty of Medicine, University of Tokyo, Tokyo 113-0033, Japan; Department
of Molecular Biosciences,*** University of Graz, 8010 Graz, Austria; Bijvoet Center and Institute of
Biomembranes,
†††
Utrecht University, 3584 CH Utrecht, The Netherlands; and The Babraham Institute,
§§§
Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom
Abstract In 2005, the International Lipid Classification
and Nomenclature Committee under the sponsorship of
the LIPID MAPS Consortium developed and established a
“Comprehensive Classification System for Lipids”based
on well-defined chemical and biochemical principles and
using an ontology that is extensible, flexible, and scalable.
This classification system, which is compatible with contem-
porary databasing and informatics needs, has now been ac-
cepted internationally and widely adopted. In response to
considerable attention and requests from lipid researchers
from around the globe and in a variety of fields, the compre-
hensive classification system has undergone significant revi-
sions over the last few years to more fully represent lipid
structures from a wider variety of sources and to provide ad-
ditional levels of detail as necessary. The details of this
classification system are reviewed and updated and are pre-
sented here, along with revisions to its suggested nomencla-
ture and structure-drawing recommendations for lipids.—Fahy,
E.,S.Subramaniam,R.C.Murphy,M.Nishijima,C.R.H.Raetz,
T.Shimizu,F.Spener,G.vanMeer,M.J.O.Wakelam,andE.A.
Dennis. Update of the LIPID MAPS comprehensive classifica-
tion system for lipids. J. Lipid Res. 2009. 50: S9–S14.
Supplementary key words lipidomics •nomenclature •structure •
databases
In an effort to support the growing field of lipidomics
and establish the importance of lipids as a major class of
biomolecules, the International Lipid Classification and
Nomenclature Committee (ILCNC) developed a “Com-
prehensive Classification System for Lipids”that was pub-
lished in 2005 (1). For the purpose of classification, we
define lipids as hydrophobic or amphipathic small mole-
cules that may originate entirely or in part by carbanion-
based condensations of thioesters (fatty acyls, glycerolipids,
glycerophospholipids, sphingolipids, saccharolipids, and
polyketides) and/or by carbocation-based condensations
of isoprene units (prenol lipids and sterol lipids). The com-
prehensive classification system organizes lipids into these
eight well-defined categories (Table 1) that cover eukary-
otic and prokaryotic sources. It has been adopted interna-
tionally and widely accepted by the lipidomics community.
The system is also available online on the LIPID MAPS
(2) website (http://www.lipidmaps.org). The comprehen-
sive classification system has been under the guidance of
the ILCNC,
3
which meets periodically to propose changes
and updates to classification, nomenclature, and struc-
tural representation.
This work was supported by the LIPID MAPS Large Scale Collaborative Grant
number GM-069338 from the National Institutes of Health.
Manuscript received 25 November 2008 and in revised form 16 December 2008
and in re-revised form 19 December 2008.
Published, JLR Papers in Press, December 19, 2008.
DOI 10.1194/jlr.R800095-JLR200
Abbreviations: ILCNC, International Lipid Classification and No-
menclature Committee; IUPAC-IUBMB, International Union of Pure
and Applied Chemists and the International Union of Biochemistry and
Molecular Biology; KEGG, Kyoto Encyclopedia of Genes and Genomes;
NCBI, National Center for Biotechnology Information.
1
Guest editor for this article was Trudy M. Forte, Childrenʼs Hospital
Oakland Research Institute.
2
To whom correspondence should be addressed.
e-mail: edennis@ucsd.edu
3
The ILCNC currently consists of Dr. Edward A. Dennis, Chair,
(US), Dr. Robert C. Murphy (US), Dr. Masahiro Nishijima ( Japan), Dr.
Christian R. H. Raetz (US), Dr. Takao Shimizu ( Japan), Dr. Friedrich
Spener (Austria), Dr. Gerrit van Meer (The Netherlands), and Dr.
Michael Wakelam (UK). Dr. Shankar Subramaniam serves as Infor-
matics Advisor, and Dr. Eoin Fahy serves as Director. Meetings were
held May 7, 2006 and May 4, 2008 in La Jolla, CA.
Copyright © 2009 by the American Society for Biochemistry and Molecular Biology, Inc.
This article is available online at http://www.jlr.org Journal of Lipid Research April Supplement, 2009 S9
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The initial version of the comprehensive classification
system was more heavily focused on mammalian lipids,
reflecting a bias toward the experimental interests of the
LIPID MAPS Consortium (2). However, due to consider-
able attention and requests from lipid researchers in a
variety of fields, the classification system has now been ex-
tended to more fully represent lipid structures from non-
mammalian sources, such as plants, bacteria, and fungi.
For example, two new main classes (Glycosyldiradylglycerols
and Glycosylmonoradylglycerols) have been added to the
Glycerolipids category to accommodate key plant structural
lipids, such as the sulfoquinovosyldiacylglycerols (3) found
in chloroplasts. Also, the list of subclasses under the Sterols
main class has been expanded to include a set of 15 differ-
ent core structures (Ergosterols, Gorgosterols, Furostanols,
etc.), which provide a structure-based classification of these
molecules that span multiple phyla.
Another key development has been the adoption of
existing hierarchies (4) for the Polyketide category and
Prenol Lipids/Isoprenoids subclasses where the majority
of these molecules are derived from natural product sources
and have been studied intensively from a pharmaceutical
and ecological standpoint. This in turn has necessitated
the expansion of the number of existing classification levels
(category, main class, and subclass) to accommodate an
additional level of stratification in the case of the C
10
to
C
30
isoprenoid subclasses that now contain entries at a
fourth level of detail. The “LM_ID”identifier, whose for-
mat provides a systematic means of assigning a unique
identification to each lipid molecule, has accordingly
been expanded in length in these particular cases, with
an additional two characters being used to describe the
fourth level.
A detailed overview of the changes and updates to the
comprehensive classification system is presented below.
CLASSIFICATION UPDATES
Expansion of LM_ID identifier
As a consequence of adding an extra level of classifica-
tion detail, the length of the LM_ID identifier was length-
ened from 12 characters to 14 in cases where a lipid defined
with four levels of classification is being described (Table 2).
In this case, characters 9 and 10 specify the level-4 class.
It should be emphasized that all lipids that do not require
a fourth level of detail (i.e., the vast majority of them) still
use a 12-digit LM_ID identifier.
Removal of classes based on lipid source
In keeping with the theme of having a classification sys-
tem dictated by molecular structure and function, the sterol
lipid subclasses Phytosterols, Marine sterols, and Fungal
sterols were retired because these refer to the lipid source
(marine) or biological kingdom (plants and fungi). It is pos-
sible to identify a particular sterol in more than one of these
three sources. These subclasses have been replaced by a new
set of subclasses based on the carbon skeleton of the sterol
core structure (Ergosterols, Gorgosterols, Furostanols, etc.).
The details are outlined under the Sterol Lipids section below,
and the complete description of this category can be found
on the LIPID MAPS website
4
(http://www.lipidmaps.org).
Adoption of existing natural products classification
hierarchies for isoprenoids and polyketides
The natural products chemistry and medicinal chemis-
try literature describes tens of thousands of molecules that
fall under the scope of lipids, based on their biosynthetic
origin. In particular, isoprenoids and polyketides from
diverse sources, such as plant, fungi, algae, bacteria, and
marine invertebrates, are well documented and have been
reviewed and classified in detail. The Dictionary of Natu-
ral Products (4), a database available from Chapman and
Hall/CRC (http://dnp.chemnetbase.com), has a classifi-
cation hierarchy that covers polyketides and isoprenoids
in depth. The LIPID MAPS comprehensive classification
system has now incorporated some of these hierarchies
relevant to natural products, with a view to covering both
mammalian and nonmammalian lipids comprehensively.
3
Expansion of classification levels
It was recognized that additional levels of stratification
were required to classify certain types of lipids and that the
current three-level system of category/main class/subclass
needed to be expanded. For example, in the Prenol Lipids
category,
3
the Sesquiterpene C
15
subclass contains ?90
known variants based on their carbon skeletons (Bisabolanes,
Germacranes, etc.). A fourth level of detail has been added
to the LIPID MAPS comprehensive classification system to
handle cases such as these.
Additional classes and subclasses
In response to worldwide interest in the comprehensive
classification system for lipids, the scope has been expanded
to cover lipids from nonmammalian sources, such as plants,
bacteria, fungi, algae, and marine organisms. To accom-
plish this, several new lipid classes have been added, such
TABLE 1. Lipid categories of the comprehensive classification system
and the number of structures in the LIPID MAPS database
Category Abbreviation Structures in Database
Fatty acyls FA 2678
Glycerolipids GL 3009
Glycerophospholipids GP 1970
Sphingolipids SP 620
Sterol Lipids ST 1744
Prenol Lipids PR 610
Saccharolipids SL 11
Polyketides PK 132
4
Supplementary tables that provide the complete list of the classes,
subclasses, and fourth class level (where applicable) of each of the eight
categories of lipids are available on the LIPID MAPS website at http://
www.lipidmaps.org.
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as fatty acyl glycosides, glycosyldiradylglycerols, and var-
ious sterol skeletons. The Polyketide category has also been
revised comprehensively.
3
NOMENCLATURE UPDATES
Changes to glycerophospholipid abbreviations
The nomenclature of lipids falls into two main catego-
ries: systematic names and common or trivial names. The
latter includes abbreviations that are a convenient way
to define acyl/alkyl chains in acylglycerols, sphingolipids,
and glycerophospholipids and synonyms such as “phos-
phatidyl”for “glycerophospho.”The generally accepted
guidelines for lipid systematic names have been defined
by the International Union of Pure and Applied Chemists
and the International Union of Biochemistry and Molecu-
lar Biology (IUPAC-IUBMB) Commission on Biochemical
Nomenclature (http://www.chem.qmul.ac.uk/iupac/)
(5–8). In response to several requests from knowledge-
able lipid experts, abbreviations for Glycerophospholipid
classes (see http://www.lipidmaps.org for GP category
3
)
have been changed now in the comprehensive classification
system to the more universally used two-letter “PC/PE/PS/
PA/P I ”format. Consequently, glycerophospholipids in the
LIPID MAPS structure database and LIPID MAPS stan-
dards database as well as all the Glycerophospholipids
drawing tools and mass spectrometry prediction tools
have been updated to conform to this new abbreviation
format (Table 3).
LIPID STRUCTURE REPRESENTATION UPDATES
The LIPID MAPS Consortium has invested considerable
effort to establish guidelines for drawing lipid structures in
a clear and consistent fashion. Large and complex lipids
are difficult to draw, which leads to the use of many unique
formats that often generate more confusion than clarity
among the lipid research community. Additionally, the
structure-drawing step is often the most time-consuming
process in creating molecular databases of lipids. However,
many classes of lipids lend themselves well as targets for
automated structure-drawing due to their consistent two-
dimensional layout. A suite of structure-drawing tools has
been developed and deployed that permits “on-demand”
generation of structures, systematic names, and abbrevia-
tions (9). The structures may be viewed and exported in a
variety of formats. Online versions of the structure-drawing
tools for fatty acyls, glycerolipids, glycerophospholipids,
sphingolipids, and sterols are available in the “Tools”sec-
tion of the LIPID MAPS website (http://www.lipidmaps.
org). Some examples of the computationally drawn struc-
tures are shown in Fig. 1.
TABLE 2. Format of LIPID MAPS identifier (LM_ID) in the comprehensive classification system
Characters Description Example Comments
1–2 Fixed “LM”designation LM Always LM
3–4 Two-letter category code PR One of eight categories
5–6 Two-digit class code 01 —
7–8 Two-digit subclass code 03 “00”when no subclass
9–10 Two-digit fourth level code 06 Only used for lipids with four levels
Last four digits Unique four-character identifier
within subclass or within fourth level
0002 First two of the last four digits are
letters in the case of the
Glycosphingolipid subclasses
TABLE 3. Changes in abbreviations for Glycerophospholipids in the comprehensive classification system
Class Synonym Old New
Glycerophosphocholines Phosphatidylcholines GPCho PC
a
Glycerophosphoethanolamines Phosphatidylethanolamines GPEtn PE
Glycerophosphoserines Phosphatidylserines GPSer PS
Glycerophosphoglycerols Phosphatidylglycerols GPGro PG
Glycerophosphoglycerophosphates Phosphatidylglycerol phosphates GPGroP PGP
Glycerophosphoinositols Phosphatidylinositols GPIns PI
Glycerophosphoinositol monophosphates Phosphatidylinositol phosphates GPInsP PIP
Glycerophosphoinositol bis-phosphates Phosphatidylinositol bis-phosphates GPInsP2 PIP2
Glycerophosphoinositol tris-phosphates Phosphatidylinositol tris-phosphates GPInsP3 PIP3
Glycerophosphates Phosphatidic acids GPA PA
Glyceropyrophosphates GPP PPA
Glycerophosphoglycerophosphoglycerols Cardiolipins CL CL
CDP-glycerols GCDP CDP-DG
Glycosylglycerophospholipids [glycan]GP [glycan]GP
Glycerophosphoinositolglycans [glycan]GPIns [glycan]PI
Glycerophosphonocholines GPnCho PnC
Glycerophosphonoethanolamines GPnEtn PnE
a
For abbreviations of monoradyglycerophospholipids (lysophospholipids), LPX may be used, for example,
LPC, LPE, LPA, etc.
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LIPID DATABASE UPDATES
Given the importance of these molecules in cellular func-
tion and pathology, it is essential to have a well-organized
database of lipids with a defined ontology that is exten-
sible, flexible, and scalable. The ontology of lipids must
incorporate classification, nomenclature, structure repre-
sentations, definitions, related biological/biophysical prop-
erties, cross-references, and structural features of all objects
stored in the database. We have developed a large publicly
available comprehensive object-relational database of lipid
structures through integration of lipid molecules from ex-
isting repositories and from the LIPID MAPS project. This
database (10, 11), in addition to serving as the most up to
date and exhaustive catalog of lipid molecules, also contains
systematic classification, nomenclature, ontology, and struc-
ture representations of lipids along with mass spectrometric
characterization where available. More than 10,000 lipid
molecules are now available on the LIPID MAPS website,
and these have been adopted by the National Center for
Biotechnology Information (NCBI) PubChem site (http://
pubchem.ncbi.nlm.nih.gov/) as well as the Kyoto Encyclo-
pedia of Genes and Genomes database (KEGG; http://
www.genome.jp/kegg/). All structures have been classified
and redrawn according to LIPID MAPS guidelines. A num-
ber of different molecular viewing formats, such as GIF im-
age, Chemdraw CDX, and the Java-based Marvin and JMol
interfaces, are offered. Where applicable, stereochemical
representation and standardized nomenclature of these
molecules are also provided. The database is accessible
through any web browser (http://www.lipidmaps.org/data/
structure/index.html) and the interfaces include text-based
and structure-based query tools.
UPDATES BY LIPID CATEGORY
Within the Fatty acyls category, the Eicosanoid sub-
classes Hydroxyeicosatrienoic acids, Hydroxyeicosatetra-
enoic acids, and Hydroxyeicosapentaenoic acids have
been changed to Hydroxy/hydroperoxyeicosatrienoic
acids, Hydroxy/hydroperoxyeicosatetraenoic acids, and
Hydroxy/hydroperoxyeicosapentaenoic acids to accom-
modate hydroperoxides. The names of the fatty amide sub-
classes N-acyl amides and N-acyl ethanolamides have been
corrected to N-acyl amines and N-acyl ethanolamines. A
new “Fatty acyl glycosides”main class has been added to
cover the great number of simple glycolipids found in
bacteria, yeast, and lower marine invertebrates (12, 13).
New subclasses include Fatty acyl glycosides of mono-
and disaccharides, Sophorolipids, and Rhamnolipids.
The Glycerolipids category was reorganized to include
two new main classes (Glycosyldiradylglycerols and Gly-
cosylmonoradylglycerols) that contain key plant structural
lipids, such as the Sulfoquinovosyldiacylglycerols found in
chloroplasts. The existing Glycerolglycoside subclasses
were removed.
Due to the fact that it is extremely difficult to experi-
mentally determine the exact position of radyl groups on
the glycerol backbone for diradylglycerols and triradylglyc-
erols, most of glycerolipid structures in the LIPID MAPS
structure database have been computationally generated.
For diradylglycerols with two different radyl groups, two
different structural isomers are possible, whereas for tri-
radylglycerols with three different radyl groups, six differ-
ent isomers exist. Instead of drawing all possible structural
isomers explicitly, an isomeric specification is used as a
descriptor. A suffix containing “iso”along with the number
of possible isomers is appended to the abbreviation (e.g.,
[iso2] and [iso6]) and a single unique LM_ID is assigned.
An example of this format is the triacylglycerol TG(16:0/
17:0/17:1(9Z))[iso6]. The structure assigned to the LM_ID
on the LIPID MAPS website corresponds to the radyl sub-
stitution shown in the abbreviation, and the option is pro-
vided to explicitly display all isomers in the group. There
are also cases within the diradyglycerol and monoradyl-
glycerol classes where enantiomeric mixtures are obtained
due to hydrolysis by certain lipases of both the sn1 or sn3
ester bond to yield 1,2-diacylglycerols[S] and 2,3-diacylglyc-
erols[R], where the stereochemical designation of the
chiral center at sn2 is reversed by the Prelog-Ingold-Cahn
rules. Furthermore, acyl migration from the sn2 position
of diacylglycerols to the primary hydroxyl group at either
sn1 or sn2 can form an isomeric diacylglycerol, viz. 1,3-
diacylglycerol. In such cases when a racemic mixture
is formed, it can be identified with a “[rac]”suffix, for
example, DG(16:0/16:0/0:0)[rac], or the stereochemis-
Fig. 1. Examples of the computationally drawn structures with sys-
tematic name, abbreviation, and lipid category illustrating the stereo-
chemical relationship between glycerolipids, glycerophospholipids,
and sphingolipids and allowing one to visualize transformations be-
tween their components.
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try is left undefined with a “[U]”suffix, for example, DG
(18:1,18:2,0:0)[U]. It should be noted that the two-
letter abbreviation (MG, DG, or TG) encompasses all
possible types of lipid chains, for example, those having
constituent acyl, alkyl, and (1Z)-alkenyl groups. The alkyl
ether linkage is represented by the “O-”prefix, for exam-
ple, DG(O-16:0/18:1(9Z)/0:0), and the (1Z)-alkenyl ether
(neutral Plasmalogen) species by the “P-”prefix, for ex-
ample, DG(P-14:0/18:1(9Z)/0:0). The same rules apply to
the headgroup classes within the Glycerophospholipids cate-
gory. In cases where glycerolipid total composition is known,
but side chain regiochemistry and stereochemistry is un-
known, abbreviations such as TG(52:1) and DG(34:2) may
be used, where the numbers within parentheses refer to the
total number of carbons and double bonds of all the chains.
For the Glycerophospholipids category, the subclass 1-
alkyl glycerophosphocholines has been replaced by the
more generic Monoalkylglycerophosphocholines due to
the fact that 1-acyl-2-alkyl-glycerophosphocholines exist in
nature. Examples are the ladderane phospholipids in
anammox bacteria (14). Similar updates have been made
for the other Glycerophospholipid headgroups. The Glyc-
erophosphoglucose lipids class has been replaced by the
Glycosylglycerophospholipids class to allow coverage of
glycerolipids with sugar groups other than glucose.
As mentioned above, we have changed to two-letter ab-
breviations (PC, PE, etc.) to describe glycerophospholipids
in shorthand form. They are generic abbreviations for all
molecular species of their respective classes. These short-
hand names lend themselves to fast, efficient, text-based
searches and are used widely in lipid research as compact
alternatives to systematic names. This “Headgroup(sn1/
sn2)”format specifies one or two radyl side chains where
the structures of the side chains are indicated within pa-
rentheses [e.g., PC(16:0/18:1(9Z)]. By default, R stereo-
chemistry is implied at the C-2 carbon of glycerol, and
the headgroup is attached at the sn3 position. In rare cases
of molecules with opposite (S) stereochemistry at C-2 of
the glycerol group and attachment of the headgroup at
the sn1 position, the stereochemistry specification of [S] is
appended to the abbreviation and the Headgroup (sn3/
sn2) abbreviation format is used. Finally, for molecules
with unknown stereochemistry at the C-2 carbon of the
glycerol group, the stereochemistry specification of [U] is
appended to the abbreviation, and the structure is drawn
with C-2 stereochemistry unspecified.
In cases where glycerophospholipid total composition is
known, but side chain regiochemistry and stereochemistry
is unknown, abbreviations, such as PE(36:1), may be used
to indicate total numbers of carbons and double bonds for
all chains. Alkyl ether and 1Z-alkenyl ether (Plasmalogen)
species are similarly represented by an “O-”or “P-”iden-
tifier, as in PC(O-36:2) and PC(P-36:1). In the latter case,
the “P-”denotes an alkyl ether linkage (typically at sn1 of
glycerol) and a double bond at the 1Z position. Monoradyl-
glycerophospholipids or lysophospholipids may be specified
with a letter “L”in the abbreviation, for example, LPC
(16:0). The synonym “phosphatidyl”(e.g., phosphatidylcho-
line) is nowadays used to refer to glycerophospholipid classes
containing all types of radyl chains and not just acyl groups
as was originally inferred by IUPAC-IUBMB guidelines (5).
The Sphingolipids classification is essentially unchanged
from that reported in the original publication in this journal
(2). One item worthy of note is that for most of the Glyco-
sphingolipid subclasses, the structure of the glycan chain
is known but the exact structure of the N-acyl side chain is
unknown. In these cases, the last two digits of the LIPID
MAPS LM_ID identifier are assigned as “00”to signify an un-
specified N-acyl side chain, and the third and fourth last dig-
its are given a different two-letter identifier for every unique
glycanchainwithinthatsubclass.Forexample,intheGan-
gliosides subclass (LM_ID: LMSP0601), the GM1 generic
structure is assigned an LM_ID of LMSP0601AP00, where
the “AP”digits specify the unique Galb1-3GalNAcb1-4
(NeuAca2-3)Galb1-4Glcbglycan chain, and the terminal
“00”digits indicate a generic ceramide structure. By con-
trast, the ganglioside GM1(12:0) has a specific N-acyl chain
and is assigned a LM_ID of LMSP0601AP01.
The Sterol lipids subclasses Phytosterols, Marine sterols,
and Fungal sterols have been removed and replaced with a
set of 13 subclasses (Ergosterols, Stigmasterols, C
24
-propyl
sterols, Gorgosterols, Furostanols, Spirostanols, Furospiro-
stanols, Cycloartanols, Calysterols, Cardanolides, Bufano-
lides, Brassinolides, and Solanidines) that differ in the
nature of their sterol core structures and cover multiple
phyla (15, 16). The vitamin D class has been appended with
the D
4
,D
5
,D
6
,andD
7
subclasses. Similarly, the Bile acid
class now includes C
22
,C
23
,C
25
,andC
29
subclasses. The
Hopanoids class has been relocated to the Prenol Lipids
category since the six-carbon D ring of the hopane core
structure is at odds with the five-carbon D ring of the other
members of the Sterol Lipids category.
The Retinoids subclass of the Prenol lipids category has
been added to the Isoprenoids class. Retinoids are a group
of C20 prenols that are related chemically to vitamin A.
They have many important functions, including roles in
vision, regulation of cell proliferation, and immunity.
As mentioned above, the C
10
to C
30
isoprenoid subclasses
now contain entries at a fourth level of detail. The corre-
sponding LM_ID identifiers contain an extra two digits that
specify the fourth level class, for example, the Bisabolane
sesquiterpenoid Zingiberene is assigned an LM_ID of
LMPR0103060002.
The Hopanoids class has been relocated to the Prenol
Lipids category (from the Sterol Lipids category).
For the Saccharolipids, the main class “Other acyl sug-
ars”has been added to cover a variety of metabolites from
plants, bacteria, and fungi. An example is the diacyl sugar
2,3-di-0-hexanoyl-a-glucopyranose from the plant species
Datura metel (17). It should be noted that this category only
covers structures in which fatty acyl/alkyl groups are
linked directly to a sugar backbone. All lipids linked to
sugars via a glycosidic bond are found in their respective
lipid-centered categories.
The Polyketides category was completely revised and
modeled on the classification hierarchy used by the Dic-
tionary of Natural Products (4). Polyketides are secondary
metabolites from bacteria, fungi, plants, and invertebrates
Lipid classification system update S13
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and have been heavily studied by natural products chem-
ists and pharmacologists for many years. The new clas-
sification format provides a better representation of the
great structural diversity within this category.
DISCUSSION
The first step toward classification of lipids is the estab-
lishment of an ontology that is extensible, flexible, and
scalable. One must be able to classify, name, and represent
these molecules in a logical manner that is amenable to
databasing and computational manipulation. The ILCNC
proposed the comprehensive classification system in 2005
and has been actively involved in enhancing and refining it
on a continuous basis. Due to considerable attention and
requests from lipid researchers in a variety of fields, the
classification system has been extended to more fully rep-
resent lipid structures from nonmammalian sources, such
as plants, bacteria, and fungi. This universal system has
been internationally accepted and is now widely used in
research and for teaching purposes. The LIPID MAPS clas-
sification system has also been adopted by KEGG, where
functional hierarchies involving lipids, reactions, and path-
ways have been constructed (http://www.genome.ad.jp/
brite/), and by the knowledgebase in Wiki format of
the EU Framework Project “LipidomicNet”(http://www.
lipidomicnet.org). In an effort to increase public avail-
ability, LIPID MAPS lipid structures are now available on
NCBIʼs PubChem website (http://pubchem.ncbi.nlm.nih.
gov), where they have been assigned PubChem Substance IDs.
The classification system is availableonline(http://
www.lipidmaps.org), where it has been integrated with an
object-relational database of .10,000 lipids. This data-
base, in addition to serving as the most up-to-date and ex-
haustive catalog of lipid molecules, also contains systematic
classification, nomenclature, ontology, and structure rep-
resentations of lipids along with mass spectrometric char-
acterization where available. All structures have been
classified and redrawn according to LIPID MAPS guide-
lines. The format of the LM_ID identifier (Table 2) pro-
vides a systematic means of simultaneously encapsulating
the classification hierarchy and assigning a unique identi-
fication to each lipid molecule. It also allows for the addition
of new classification elements in the future. The database is
accessible through any web browser, and the interfaces in-
clude text-based and structure-based query tools. This data-
base is described in detail elsewhere (10, 11).
A suite of lipid structure-drawing tools (available in the
Tools section of the LIPID MAPS website) has been devel-
oped to enable rapid structure generation consistent with
LIPID MAPS guidelines. These tools are also capable of
generating systematic names and detailed ontologies, en-
abling rapid and efficient databasing of lipid molecules.
Unix-based and web-based software has been created to
register and edit database records and to automatically clas-
sify and assign LIPID MAPS IDs. These tools will be ex-
panded and refined as the scope of the classification system
and databases evolves over the coming years.
The authors appreciate the input of numerous lipid researchers
around the world who have made valuable suggestions and
brought to our attention anomalies in the original Comprehen-
sive Classification System for Lipids, which to be useful must
constantly adapt to new information and advances in the lipid
field. The authors are also grateful to the entire LIPID MAPS
Consortium for their input and especially to Dr. Jean Chin, Pro-
gram Director at the National Institutes of General Medical
Sciences, for her valuable input to this effort.
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