Copyright © 2005 by the American Society for Biochemistry and Molecular Biology, Inc.
This article is available online at http://www.jlr.org
Journal of Lipid Research
Volume 46, 2005
839
A comprehensive classification system for lipids
1
Eoin Fahy,* Shankar Subramaniam,
†
H. Alex Brown,
§
Christopher K. Glass,**
Alfred H. Merrill, Jr.,
††
Robert C. Murphy,
§§
Christian R. H. Raetz,*** David W. Russell,
†††
Yousuke Seyama,
§§§
Walter Shaw,**** Takao Shimizu,
††††
Friedrich Spener,
§§§§
Gerrit van Meer,***** Michael S. VanNieuwenhze,
†††††
Stephen H. White,
§§§§§
Joseph L. Witztum,****** and Edward A. Dennis
2,††††††
San Diego Supercomputer Center,* University of California, San Diego, 9500 Gilman Drive, La Jolla, CA
92093-0505; Department of Bioengineering,
†
University of California, San Diego, 9500 Gilman Drive, La Jolla,
CA 92093-0412; Department of Pharmacology,
§
Vanderbilt University Medical Center, Nashville, TN 37232-
6600; Department of Cellular and Molecular Medicine,** University of California, San Diego, 9500 Gilman
Drive, La Jolla, CA 92093-0651; School of Biology,
††
Georgia Institute of Technology, Atlanta, GA 30332-0230;
Department of Pharmacology,
§§
University of Colorado Health Sciences Center, Aurora, CO 80045-0508;
Department of Biochemistry,*** Duke University Medical Center, Durham, NC 27710; Department of
Molecular Genetics,
†††
University of Texas Southwestern Medical Center, Dallas, TX 75390-9046; Faculty of
Human Life and Environmental Sciences,
§§§
Ochanomizu University, Tokyo 112-8610, Japan; Avanti Polar
Lipids, Inc.,**** Alabaster, AL 35007; 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; Department of Membrane Enzymology,***** Institute of Biomembranes, Utrecht
University, 3584 CH Utrecht, The Netherlands; Department of Chemistry and Biochemistry,
†††††
University of
California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358; Department of Physiology and
Biophysics,
§§§§§
University of California at Irvine, Irvine, CA 92697-4560; Department of Medicine,******
University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0682; and Department of
Chemistry and Biochemistry and Department of Pharmacology,
††††††
University of California, San Diego,
La Jolla, CA 92093-0601
Abstract Lipids are produced, transported, and recognized
by the concerted actions of numerous enzymes, binding pro-
teins, and receptors. A comprehensive analysis of lipid mol-
ecules, “lipidomics,” in the context of genomics and pro-
teomics is crucial to understanding cellular physiology and
pathology; consequently, lipid biology has become a major
research target of the postgenomic revolution and systems
biology. To facilitate international communication about lip-
ids, a comprehensive classification of lipids with a common
platform that is compatible with informatics requirements
has been developed to deal with the massive amounts of data
that will be generated by our lipid community. As an initial
step in this development, we divide lipids into eight catego-
ries (fatty acyls, glycerolipids, glycerophospholipids, sphin-
golipids, sterol lipids, prenol lipids, saccharolipids, and poly-
ketides) containing distinct classes and subclasses of molecules,
devise a common manner of representing the chemical struc-
tures of individual lipids and their derivatives, and provide
a 12 digit identifier for each unique lipid molecule. The lipid
classification scheme is chemically based and driven by the
distinct hydrophobic and hydrophilic elements that com-
pose the lipid. This structured vocabulary will facilitate the
systematization of lipid biology and enable the cataloging of
lipids and their properties in a way that is compatible with
other macromolecular databases.
—Fahy, E., S. Subramaniam,
H. A. Brown, C. K. Glass, A. H. Merrill, Jr., R. C. Murphy,
C. R. H. Raetz, D. W. Russell, Y. Seyama, W. Shaw, T. Shimizu,
F. Spener, G. van Meer, M. S. VanNieuwenhze, S. H. White,
J. L. Witztum, and E. A. Dennis.
A comprehensive classifica-
tion system for lipids.
J. Lipid Res.
2005.
46:
839–861.
Supplementary key words
lipidomics
•
informatics
•
nomenclature
•
chemical representation
•
fatty acyls
•
glycerolipids
•
glycerophospho-
lipids
•
sphingolipids
•
sterol lipids
•
prenol lipids
•
saccharolipids
•
polyketides
The goal of collecting data on lipids using a “systems bi-
ology” approach to lipidomics requires the development
of a comprehensive classification, nomenclature, and chem-
ical representation system to accommodate the myriad lip-
ids that exist in nature. Lipids have been loosely defined
as biological substances that are generally hydrophobic in
nature and in many cases soluble in organic solvents (1).
These chemical properties cover a broad range of mole-
1
The evaluation of this manuscript was handled by the former
Editor-in-Chief Trudy Forte.
2
To whom correspondence should be addressed.
e-mail: edennis@ucsd.edu
Manuscript received 22 December 2004 and in revised form 4 February 2005.
Published, JLR Papers in Press, February 16, 2005.
DOI 10.1194/jlr.E400004-JLR200
840 Journal of Lipid Research
Volume 46, 2005
cules, such as fatty acids, phospholipids, sterols, sphingolip-
ids, terpenes, and others (2). The LIPID MAPS (LIPID Me-
tabolites And Pathways Strategy; http://www.lipidmaps.org),
Lipid Library (http://lipidlibrary.co.uk), Lipid Bank (http://
lipidbank.jp), LIPIDAT (http://www.lipidat.chemistry.ohio-
state.edu), and Cyberlipids (http://www.cyberlipid.org)
websites provide useful online resources for an overview of
these molecules and their structures. More accurate defi-
nitions are possible when lipids are considered from a
structural and biosynthetic perspective, and many differ-
ent classification schemes have been used over the years.
However, for the purpose of comprehensive classification,
we define lipids as hydrophobic or amphipathic small
molecules that may originate entirely or in part by car-
banion-based condensations of thioesters (fatty acids,
polyketides, etc.) and/or by carbocation-based condensa-
tions of isoprene units (prenols, sterols, etc.). Addition-
ally, lipids have been broadly subdivided into “simple” and
“complex” groups, with simple lipids being those yielding
at most two types of products on hydrolysis (e.g., fatty ac-
ids, sterols, and acylglycerols) and complex lipids (e.g.,
glycerophospholipids and glycosphingolipids) yielding three
or more products on hydrolysis. The classification scheme
presented here organizes lipids into well-defined catego-
ries that cover eukaryotic and prokaryotic sources and
that is equally applicable to archaea and synthetic (man-
made) lipids.
Lipids may be categorized based on their chemically func-
tional backbone as polyketides, acylglycerols, sphingolip-
ids, prenols, or saccharolipids. However, for historical and
bioinformatics advantages, we chose to separate fatty acyls
from other polyketides, the glycerophospholipids from
the other glycerolipids, and sterol lipids from other pre-
nols, resulting in a total of eight primary categories. An
important aspect of this scheme is that it allows for subdi-
vision of the main categories into classes and subclasses to
handle the existing and emerging arrays of lipid struc-
tures. Although any classification scheme is in part subjec-
tive as a result of the structural and biosynthetic complexity
of lipids, it is an essential prerequisite for the organization
of lipid research and the development of systematic meth-
ods of data management. The classification scheme pre-
sented here is chemically based and driven by the distinct
hydrophobic and hydrophilic elements that constitute the
lipid. Biosynthetically related compounds that are not
technically lipids because of their water solubility are in-
cluded for completeness in this classification scheme.
The proposed lipid categories listed in
Table 1
have
names that are, for the most part, well accepted in the lit-
erature. The fatty acyls (FA) are a diverse group of mole-
cules synthesized by chain elongation of an acetyl-CoA
primer with malonyl-CoA (or methylmalonyl-CoA) groups
that may contain a cyclic functionality and/or are substi-
tuted with heteroatoms. Structures with a glycerol group
are represented by two distinct categories: the glycerolip-
ids (GL), which include acylglycerols but also encompass
alkyl and 1
Z
-alkenyl variants, and the glycerophospholipids
(GP), which are defined by the presence of a phosphate
(or phosphonate) group esterified to one of the glycerol
hydroxyl groups. The sterol lipids (ST) and prenol lipids
(PR) share a common biosynthetic pathway via the poly-
merization of dimethylallyl pyrophosphate/isopentenyl
pyrophosphate but have obvious differences in terms of
their eventual structure and function. Another well-defined
category is the sphingolipids (SP), which contain a long-
chain base as their core structure. This classification does
not have a glycolipids category per se but rather places
glycosylated lipids in appropriate categories based on the
identity of their core lipids. It also was necessary to define
a category with the term “saccharolipids” (SL) to account
for lipids in which fatty acyl groups are linked directly to a
sugar backbone. This SL group is distinct from the term
“glycolipid” that was defined by the International Union
of Pure and Applied Chemists (IUPAC) as a lipid in which
the fatty acyl portion of the molecule is present in a glyco-
sidic linkage. The final category is the polyketides (PK),
which are a diverse group of metabolites from plant and mi-
crobial sources. Protein modification by lipids (e.g., fatty acyl,
prenyl, cholesterol) occurs in nature; however, these pro-
teins are not included in this database but are listed in
protein databases such as GenBank (http://www.ncbi.nlm.
nih.gov) and SwissProt (http://www.ebi.ac.uk/swissprot/).
LIPID NOMENCLATURE
A naming scheme must unambiguously define a lipid
structure in a manner that is amenable to chemists, biol-
ogists, and biomedical researchers. The issue of lipid no-
menclature was last addressed in detail by the Inter-
national Union of Pure and Applied Chemists and the
International Union of Biochemistry and Molecular Biol-
ogy (IUPAC-IUBMB) Commission on Biochemical No-
menclature in 1976, which subsequently published its rec-
ommendations (3). Since then, a number of additional
documents relating to the naming of glycolipids (4), pre-
nols (5), and steroids (6) have been released by this com-
mission and placed on the IUPAC website (http://www.
chem.qmul.ac.uk/iupac/). A large number of novel lipid
classes have been discovered during the last three decades
that have not yet been systematically named. The present
classification includes these new lipids and incorporates a
consistent nomenclature.
In conjunction with our proposed classification scheme,
we provide examples of systematic (or semisystematic)
names for the various classes and subclasses of lipids. The
nomenclature proposal follows existing IUPAC-IUBMB
rules closely and should not be viewed as a competing for-
mat. The main differences involve
a
) clarification of the
use of core structures to simplify systematic naming of
some of the more complex lipids, and
b
) provision of sys-
tematic names for recently discovered lipid classes.
Key features of our lipid nomenclature scheme are as
follows:
a
) The use of the stereospecific numbering (
sn
) method
to describe glycerolipids and glycerophospholipids (3). The
glycerol group is typically acylated or alkylated at the
sn
-1
and/or
sn
-2 position, with the exception of some lipids
Fahy et al.
Lipid classification system 841
that contain more than one glycerol group and archaebac-
terial lipids in which
sn
-2 and/or
sn
-3 modification occurs.
b
) Definition of sphinganine and sphing-4-enine as core
structures for the sphingolipid category, where the
d
-
erythro
or 2
S
,3
R
configuration and 4
E
geometry (in the case of
sphing-4-enine) are implied. In molecules containing ste-
reochemistries other than the 2
S
,3
R
configuration, the full
systematic names are to be used instead (e.g., 2
R
-amino-
1,3
R
-octadecanediol).
c
) The use of core names such as cholestane, andro-
stane, and estrane for sterols.
d
) Adherence to the names for fatty acids and acyl chains
(formyl, acetyl, propionyl, butyryl, etc.) defined in Appen-
dices A and B of the IUPAC-IUBMB recommendations (3).
Fig. 1. Representative structures for each lipid category.
TABLE 1. Lipid categories and examples
Category Abbreviation Example
Fatty acyls FA dodecanoic acid
Glycerolipids GL 1-hexadecanoyl-2-(9
Z
-octadecenoyl)-
sn
-glycerol
Glycerophospholipids GP 1-hexadecanoyl-2-(9
Z
-octadecenoyl)-
sn
-glycero-3-phosphocholine
Sphingolipids SP
N
-(tetradecanoyl)-sphing-4-enine
Sterol lipids ST cholest-5-en-3
-ol
Prenol lipids PR 2
E
,6
E
-farnesol
Saccharolipids SL UDP-3-
O
-(3
R
-hydroxy-tetradecanoyl)-
d
-
N
-acetylglucosamine
Polyketides PK aflatoxin B
1
842 Journal of Lipid Research
Volume 46, 2005
e
) The adoption of a condensed text nomenclature for
the glycan portions of lipids, where sugar residues are rep-
resented by standard IUPAC abbreviations and where the
anomeric carbon locants and stereochemistry are included
but the parentheses are omitted. This system has also been
proposed by the Consortium for Functional Glycomics
(http://web.mit.edu/glycomics/consortium/main.shtml).
f
) The use of
E
/
Z
designations (as opposed to
trans
/
cis
)
to define double bond geometry.
g
) The use of
R
/
S
designations (as opposed to
/
or
d
/
l
) to define stereochemistries. The exceptions are those
describing substituents on glycerol (
sn
) and sterol core
structures and anomeric carbons on sugar residues. In
these latter special cases, the
/
format is firmly estab-
lished.
h
) The common term “lyso,” denoting the position lack-
ing a radyl group in glycerolipids and glycerophospholip-
ids, will not be used in systematic names but will be in-
cluded as a synonym.
i
) The proposal for a single nomenclature scheme to
cover the prostaglandins, isoprostanes, neuroprostanes,
and related compounds, where the carbons participating
in the cyclopentane ring closure are defined and where a
consistent chain-numbering scheme is used.
j
) The “d” and “t” designations used in shorthand nota-
tion of sphingolipids refer to 1,3-dihydroxy and 1,3,4-tri-
hydroxy long-chain bases, respectively.
LIPID STRUCTURE REPRESENTATION
In addition to having rules for lipid classification and
nomenclature, it is important to establish clear guidelines
for drawing lipid structures. Large and complex lipids are
difficult to draw, which leads to the use of shorthand and
unique formats that often generate more confusion than
clarity among lipidologists. We propose a more consistent
format for representing lipid structures in which, in the
simplest case of the fatty acid derivatives, the acid group
(or equivalent) is drawn on the right and the hydrophobic
hydrocarbon chain is on the left (
Fig. 1
). Notable exceptions
are found in the eicosanoid class, in which the hydrocarbon
chain wraps around in a counterclockwise direction to pro-
duce a more condensed structure. Similarly, with regard to
the glycerolipids and glycerophospholipids, the radyl chains
are drawn with the hydrocarbon chains to the left and the
glycerol group depicted horizontally with stereochemistry
at the
sn
carbons defined (if known). The general term
“radyl” is used to denote either acyl, alkyl, or 1-alkenyl sub-
stituents (http://www.chem.qmul.ac.uk/iupac/lipid/lip1n2.
html), allowing for coverage of alkyl and 1
Z
-alkenylglycerols.
The sphingolipids, although they do not contain a glycerol
group, have a similar structural relationship to the glycero-
phospholipids in many cases and may be drawn with the
C1 hydroxyl group of the long-chain base to the right and
the alkyl portion to the left. This methodology places the
head groups of both sphingolipids and glycerophospho-
TABLE 3. Shorthand notation for selected lipid categories
Category Abbreviation Class or Subclass Example
a
GP GPCho Glycerophosphocholines GPCho (16:0/9
Z
,12
Z
-18:2)
GP GPnCho Glycerophosphonocholines
GP GPEtn Glycerophosphoethanolamines
GP GPnEtn Glycerophosphonoethanolamines
GP GPSer Glycerophosphoserines
GP GPGro Glycerophosphoglycerols
GP GPGroP Glycerophosphoglycerophosphates
GP GPIns Glycerophosphoinositols
GP GPInsP Glycerophosphoinositol monophosphates
GP GPInsP
2
Glycerophosphoinositol bis-phosphates
GP GPInsP
3
Glycerophosphoinositol tris-phosphates
GP GPA Glycerophosphates
GP GPP Glyceropyrophosphates
GP CL Glycerophosphoglycerophosphoglycerols
GP CDP-DG CDP-glycerols
GP [glycan]GP Glycerophosphoglucose lipids
GP [glycan]GPIns Glycerophosphoinositolglycans EtN-P-6Man
1
2Man
1
6 Man
1
4GlcN
1-6GPIns (14:0/14:0)
SP Cer Ceramides Cer (d18:1/9
E
-16:1)
SP SM Phosphosphingolipids SM (d18:1/24:0)
SP [glycan]Cer Glycosphingolipids NeuAc
2
3Gal
1
4Glc
-Cer (d18:1/16:0)
GL MG Monoradyl glycerols MG (16:0/0:0/0:0)
GL DG Diradyl glycerols DG (18:0/16:0/0:0)
GL TG Triradyl glycerols TG (12:0/14:0/18:0)
a
Shorthand notation for radyl substituents in categories GP and GL are presented in the order of
sn
-1 to
sn
-3. Shorthand notation for category
SP is presented in the order of long-chain base and
N
-acyl substituent. Numbers separated by colons refer to carbon chain length and number of
double bonds, respectively.
TABLE 2. Format of 12 character LIPID ID
Characters Description Example
1–2 Fixed database designation LM
3–4 Two letter category code FA
5–6 Two digit class code 03
7–8 Two digit subclass code 02
9–12 Unique four character identifier within subclass 7312
Fahy et al.
Lipid classification system 843
lipids on the right side. Although the structures of sterols
do not conform to these general rules of representation, the
sterol esters may conveniently be drawn with the acyl group
oriented according to these guidelines. In addition, the
linear prenols or isoprenoids are drawn in a manner anal-
ogous to the fatty acids, with the terminal functional group
on the right side. Inevitably, a number of structurally com-
plex lipids, such as acylaminosugar glycans, polycyclic iso-
prenoids, and polyketides, do not lend themselves to these
simplified drawing rules. Nevertheless, we believe that the
adoption of the guidelines proposed here will unify chem-
ical representation and make it more comprehensible.
DATABASING LIPIDS, ANNOTATION,
AND FUNCTION
A number of repositories, such as GenBank, SwissProt,
and ENSEMBL (http://www.ensembl.org), support nu-
cleic acid and protein databases; however, there are only a
few specialized databases [e.g., LIPIDAT (7) and Lipid
Bank (8)] that provide a catalog, annotation, and func-
tional classification of lipids. Given the importance of
these molecules in cellular function and pathology, there
is an imminent need for the creation of a well-organized
database of lipids. The first step toward this goal is the es-
tablishment of an ontology of lipids that is extensible,
flexible, and scalable. Before establishing an ontology, a
structured vocabulary is needed, and the IUPAC nomen-
clature of the 1970s was an initial step in this direction.
The ontology of lipids must contain definitions, mean-
ings, and interrelationships of all objects stored in the da-
tabase. This ontology is then transformed into a well-
defined schema that forms the foundation for a relational
database of lipids. The LIPID MAPS project is building a
robust database of lipids based on the proposed ontology.
Our database will provide structural and functional an-
notations and have links to relevant protein and gene
data. In addition, a universal data format (XML) will be
provided to facilitate exportation of the data into other re-
positories. This database will enable the storage of curated
information on lipids in a web-accessible format and will
provide a community standard for lipids.
An important database field will be the LIPID ID, a
unique 12 character identifier based on the classification
scheme described here. The format of the LIPID ID, out-
lined in
Table 2
, provides a systematic means of assigning
unique IDs to lipid molecules and allows for the addition
of large numbers of new categories, classes, and subclasses
in the future, because a maximum of 100 classes/subclasses
(00 to 99) may be specified. The last four characters of the
TABLE 4. Fatty acyls [FA] classes and subclasses
Fatty acids and conjugates [FA01]
Straight-chain fatty acids [FA0101]
Methyl branched fatty acids [FA0102]
Unsaturated fatty acids [FA0103]
Hydroperoxy fatty acids [FA0104]
Hydroxy fatty acids [FA0105]
Oxo fatty acids [FA0106]
Epoxy fatty acids [FA0107]
Methoxy fatty acids [FA0108]
Halogenated fatty acids [FA0109]
Amino fatty acids [FA0110]
Cyano fatty acids [FA0111]
Nitro fatty acids [FA0112]
Thia fatty acids [FA0113]
Carbocyclic fatty acids [FA0114]
Heterocyclic fatty acids [FA0115]
Mycolic acids [FA0116]
Dicarboxylic acids [FA0117]
Octadecanoids [FA02]
12-Oxophytodienoic acid metabolites [FA0201]
Jasmonic acids [FA0202]
Eicosanoids [FA03]
Prostaglandins [FA0301]
Leukotrienes [FA0302]
Thromboxanes [FA0303]
Lipoxins [FA0304]
Hydroxyeicosatrienoic acids [FA0305]
Hydroxyeicosatetraenoic acids [FA0306]
Hydroxyeicosapentaenoic acids [FA0307]
Epoxyeicosatrienoic acids [FA0308]
Hepoxilins [FA0309]
Levuglandins [FA0310]
Isoprostanes [FA0311]
Clavulones [FA0312]
Docosanoids [FA04]
Fatty alcohols [FA05]
Fatty aldehydes [FA06]
Fatty esters [FA07]
Wax monoesters [FA0701]
Wax diesters [FA0702]
Cyano esters [FA0703]
Lactones [FA0704]
Fatty acyl-CoAs [FA0705]
Fatty acyl-acyl carrier proteins (ACPs) [FA0706]
Fatty acyl carnitines [FA0707]
Fatty acyl adenylates [FA0708]
Fatty amides [FA08]
Primary amides [FA0801]
N
-Acyl amides [FA0802]
Fatty acyl homoserine lactones [FA0803]
N
-Acyl ethanolamides (endocannabinoids) [FA0804]
Fatty nitriles [FA09]
Fatty ethers [FA10]
Hydrocarbons [FA11]
Oxygenated hydrocarbons [FA12]
Other [FA00]
TABLE 5. Glycerolipids [GL] classes and subclasses
Monoradylglycerols [GL01]
Monoacylglycerols [GL0101]
Monoalkylglycerols [GL0102]
Mono-(1
Z
-alkenyl)-glycerols [GL0103]
Monoacylglycerolglycosides [GL0104]
Monoalkylglycerolglycosides [GL0105]
Diradylglycerols [GL02]
Diacylglycerols [GL0201]
Alkylacylglycerols [GL0202]
Dialkylglycerols [GL0203]
1
Z
-Alkenylacylglycerols [GL0204]
Diacylglycerolglycosides [GL0205]
Alkylacylglycerolglycosides [GL0206]
Dialkylglycerolglycosides [GL0207]
Di-glycerol tetraethers [GL0208]
Di-glycerol tetraether glycans [GL0209]
Triradylglycerols [GL03]
Triacylglycerols [GL0301]
Alkyldiacylglycerols [GL0302]
Dialkylmonoacylglycerols [GL0303]
1Z-Alkenyldiacylglycerols [GL0304]
Estolides [GL0305]
Other [GL00]
![TABLE 6. Glycerophospholipids [GP] classes and subclasses](/figures/table-6-glycerophospholipids-gp-classes-and-subclasses-2urneip2.webp)
![TABLE 10. Saccharolipids [SL] classes and subclasses](/figures/table-10-saccharolipids-sl-classes-and-subclasses-1lb6zuyv.webp)
![TABLE 11. Polyketides [PK] classes and subclasses](/figures/table-11-polyketides-pk-classes-and-subclasses-2ty505oo.webp)
