A comprehensive classification system for lipids

Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid molecules, “lipidomics,” in the context of genomics and proteomics 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 lipids, 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 categories (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides) containing distinct classes and subclasses of molecules, devise a common manner of representing the chemical structures 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 compose 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. Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid molecules, “lipidomics,” in the context of genomics and proteomics 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 lipids, 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 categories (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides) containing distinct classes and subclasses of molecules, devise a common manner of representing the chemical structures 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 compose 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. The goal of collecting data on lipids using a “systems biology” approach to lipidomics requires the development of a comprehensive classification, nomenclature, and chemical representation system to accommodate the myriad lipids 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 (1Smith A. Oxford Dictionary of Biochemistry and Molecular Biology. 2nd edition. Oxford University Press, Oxford, UK2000Google Scholar). These chemical properties cover a broad range of molecules, such as fatty acids, phospholipids, sterols, sphingolipids, terpenes, and others (2Christie W.W. Lipid Analysis. 3rd edition. Oily Press, Bridgewater, UK2003Google Scholar). The LIPID MAPS (LIPID Metabolites 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 definitions are possible when lipids are considered from a structural and biosynthetic perspective, and many different 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 carbanion-based condensations of thioesters (fatty acids, polyketides, etc.) and/or by carbocation-based condensations of isoprene units (prenols, sterols, etc.). Additionally, 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 acids, 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 categories that cover eukaryotic and prokaryotic sources and that is equally applicable to archaea and synthetic (manmade) lipids. Lipids may be categorized based on their chemically functional backbone as polyketides, acylglycerols, sphingolipids, 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 prenols, resulting in a total of eight primary categories. An important aspect of this scheme is that it allows for subdivision of the main categories into classes and subclasses to handle the existing and emerging arrays of lipid structures. Although any classification scheme is in part subjective 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 methods of data management. The classification scheme presented 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 included 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 literature. The fatty acyls (FA) are a diverse group of molecules 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 substituted with heteroatoms. Structures with a glycerol group are represented by two distinct categories: the glycerolipids (GL), which include acylglycerols but also encompass alkyl and 1Z-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 polymerization 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 glycosidic linkage. The final category is the polyketides (PK), which are a diverse group of metabolites from plant and microbial sources. Protein modification by lipids (e.g., fatty acyl, prenyl, cholesterol) occurs in nature; however, these proteins 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/).TABLE 1Lipid categories and examplesCategoryAbbreviationExampleFatty acyls FAdodecanoic acidGlycerolipids GL1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerolGlycerophospholipids GP1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholineSphingolipids SPN-(tetradecanoyl)-sphing-4-enineSterol lipids STcholest-5-en-3β-olPrenol lipids PR2E,6E-farnesolSaccharolipids SLUDP-3-O-(3R-hydroxy-tetradecanoyl)-αd-N-acetylglucosaminePolyketides PKaflatoxin B1 Open table in a new tab A naming scheme must unambiguously define a lipid structure in a manner that is amenable to chemists, biologists, and biomedical researchers. The issue of lipid nomenclature was last addressed in detail by the International Union of Pure and Applied Chemists and the International Union of Biochemistry and Molecular Biology (IUPAC-IUBMB) Commission on Biochemical Nomenclature in 1976, which subsequently published its recommendations (3IUPAC-IUB Commission on Biochemical Nomenclature (CBN). The nomenclature of lipids (recommendations 1976). 1977. Eur. J. Biochem. 79: 11–21; 1977. Hoppe-Seylers Z. Physiol. Chem. 358: 617–631; 1977. Lipids. 12: 455–468; 1977. Mol. Cell. Biochem. 17: 157–171; 1978. Chem. Phys. Lipids. 21: 159–173; 1978. J. Lipid Res. 19: 114–128; 1978. Biochem. J. 171: 21–35 (http://www.chem.qmul. ac.uk/iupac/lipid/).Google Scholar). Since then, a number of additional documents relating to the naming of glycolipids (4IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of glycolipids (recommendations 1997). 2000. Adv. Carbohydr. Chem. Biochem. 55: 311–326; 1988. Carbohydr. Res. 312: 167–175; 1998. Eur. J. Biochem. 257: 293–298; 1999. Glycoconjugate J. 16: 1–6; 1999. J. Mol. Biol. 286: 963–970; 1997. Pure Appl. Chem. 69: 2475–2487 (http://www.chem.qmul.ac.uk/iupac/misc/glylp.html).Google Scholar), prenols (5IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). 1987. Nomenclature of prenols (recommendations 1987). Eur. J. Biochem. 167: 181–184 (http://www.chem.qmul.ac.uk/iupac/misc/prenol.html).Google Scholar), and steroids (6IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). 1989. Nomenclature of steroids (recommendations 1989). Eur. J. Biochem. 186: 429–458 (http://www.chem.qmul.ac.uk/iupac/steroid/).Google Scholar) have been released by this commission 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 format. 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 systematic 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 (3IUPAC-IUB Commission on Biochemical Nomenclature (CBN). The nomenclature of lipids (recommendations 1976). 1977. Eur. J. Biochem. 79: 11–21; 1977. Hoppe-Seylers Z. Physiol. Chem. 358: 617–631; 1977. Lipids. 12: 455–468; 1977. Mol. Cell. Biochem. 17: 157–171; 1978. Chem. Phys. Lipids. 21: 159–173; 1978. J. Lipid Res. 19: 114–128; 1978. Biochem. J. 171: 21–35 (http://www.chem.qmul. ac.uk/iupac/lipid/).Google Scholar). The glycerol group is typically acylated or alkylated at the sn-1 and/or sn-2 position, with the exception of some lipids that contain more than one glycerol group and archaebacterial 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 2S,3R configuration and 4E geometry (in the case of sphing-4-enine) are implied. In molecules containing stereochemistries other than the 2S,3R configuration, the full systematic names are to be used instead (e.g., 2R-amino-1,3R-octadecanediol). c) The use of core names such as cholestane, androstane, and estrane for sterols. d) Adherence to the names for fatty acids and acyl chains (formyl, acetyl, propionyl, butyryl, etc.) defined in Appendices A and B of the IUPAC-IUBMB recommendations (3IUPAC-IUB Commission on Biochemical Nomenclature (CBN). The nomenclature of lipids (recommendations 1976). 1977. Eur. J. Biochem. 79: 11–21; 1977. Hoppe-Seylers Z. Physiol. Chem. 358: 617–631; 1977. Lipids. 12: 455–468; 1977. Mol. Cell. Biochem. 17: 157–171; 1978. Chem. Phys. Lipids. 21: 159–173; 1978. J. Lipid Res. 19: 114–128; 1978. Biochem. J. 171: 21–35 (http://www.chem.qmul. ac.uk/iupac/lipid/).Google Scholar). e) The adoption of a condensed text nomenclature for the glycan portions of lipids, where sugar residues are represented 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 α/β 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 α/β format is firmly established. h) The common term “lyso,” denoting the position lacking a radyl group in glycerolipids and glycerophospholipids, will not be used in systematic names but will be included 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 notation of sphingolipids refer to 1,3-dihydroxy and 1,3,4-trihydroxy long-chain bases, respectively. 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 produce 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 substituents (http://www.chem.qmul.ac.uk/iupac/lipid/lip1n2.html), allowing for coverage of alkyl and 1Z-alkenylglycerols. The sphingolipids, although they do not contain a glycerol group, have a similar structural relationship to the glycerophospholipids 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 glycerophospholipids 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 analogous to the fatty acids, with the terminal functional group on the right side. Inevitably, a number of structurally complex lipids, such as acylaminosugar glycans, polycyclic isoprenoids, and polyketides, do not lend themselves to these simplified drawing rules. Nevertheless, we believe that the adoption of the guidelines proposed here will unify chemical representation and make it more comprehensible. A number of repositories, such as GenBank, SwissProt, and ENSEMBL (http://www.ensembl.org), support nucleic acid and protein databases; however, there are only a few specialized databases [e.g., LIPIDAT (7Caffrey M. Hogan J. LIPIDAT: a database of lipid phase transition temperatures and enthalpy changes.Chem. Phys. Lipids. 1992; 61 (http://www.lipidat.chemistry.ohio-state.edu): 1-109Crossref PubMed Scopus (108) Google Scholar) and Lipid Bank (8Watanabe K. Yasugi E. Ohshima M. How to search the glycolipid data in “Lipidbank for web,” the newly-developed lipid database in Japan.Trends Gycosci. Glycotechnol. 2000; 12: 175-184Crossref Scopus (54) Google Scholar)] that provide a catalog, annotation, and functional 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 establishment of an ontology of lipids that is extensible, flexible, and scalable. Before establishing an ontology, a structured vocabulary is needed, and the IUPAC nomenclature of the 1970s was an initial step in this direction. The ontology of lipids must contain definitions, meanings, and interrelationships of all objects stored in the database. 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 annotations 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 repositories. 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, outlined 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 ID constitute a unique identifier within a particular subclass and are randomly assigned. By initially using numeric characters, this allows 9,999 unique IDs per subclass, but with the additional use of 26 uppercase alphabetic characters, a total of 1.68 million possible combinations can be generated, providing ample scalability within each subclass. In cases in which lipid structures are obtained from other sources such as LipidBank or LIPIDAT, the corresponding IDs for those databases will be included to enable cross-referencing. The first two characters of the ID contain the database identifier (e.g., LM for LIPID MAPS), although other databases may choose to use their own two character identifier (at present, LB for Lipid Bank and LD for LIPIDAT) and assign the last four or more characters uniquely while retaining characters 3 to 8, which pertain to classification. The corresponding IDs of the other databases will always be included to enable cross-referencing. Further details regarding the numbering system will be decided by the International Lipids Classification and Nomenclature Committee (see below). In addition to the LIPID ID, each lipid in the database will be searchable by classification (category, class, subclass), systematic name, synonym(s), molecular formula, molecular weight, and many other parameters that are part of its ontology. An important feature will be the databasing of molecular structures, allowing the user to perform web-based substructure searches and structure retrieval across the database. This aim will be accomplished with a chemistry cartridge software component that will enable structures in formats such as MDL molfile and Chemdraw CDX to be imported directly into Oracle database tables.TABLE 2Format of 12 character LIPID IDCharactersDescriptionExample1–2Fixed database designation LM3–4Two letter category code FA5–6Two digit class code037–8Two digit subclass code029–12Unique four character identifier within subclass7312 Open table in a new tab Furthermore, many lipids, in particular the glycerolipids, glycerophospholipids, and sphingolipids, may be conveniently described in terms of a shorthand name in which abbreviations are used to define backbones, head groups, and sugar units and the radyl substituents are defined by a descriptor indicating carbon chain length and number of double bonds. These shorthand names lend themselves to fast, efficient text-based searches and are used widely in lipid research as compact alternatives to systematic names. The glycerophospholipids in the LIPIDAT database, for example, may be conveniently searched with a shorthand notation that has been extended to handle side chains with acyl, ether, branched-chain, and other functional groups (7Caffrey M. Hogan J. LIPIDAT: a database of lipid phase transition temperatures and enthalpy changes.Chem. Phys. Lipids. 1992; 61 (http://www.lipidat.chemistry.ohio-state.edu): 1-109Crossref PubMed Scopus (108) Google Scholar). We propose the use of a shorthand notation for selected lipid categories (Table 3) that incorporates a condensed text nomenclature for glycan substituents. The abbreviations for the sugar units follow the current IUPAC-IUBMB recommendations (4IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of glycolipids (recommendations 1997). 2000. Adv. Carbohydr. Chem. Biochem. 55: 311–326; 1988. Carbohydr. Res. 312: 167–175; 1998. Eur. J. Biochem. 257: 293–298; 1999. Glycoconjugate J. 16: 1–6; 1999. J. Mol. Biol. 286: 963–970; 1997. Pure Appl. Chem. 69: 2475–2487 (http://www.chem.qmul.ac.uk/iupac/misc/glylp.html).Google Scholar).TABLE 3Shorthand notation for selected lipid categoriesCategoryAbbreviationClass or SubclassExampleaShorthand 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.GPGPChoGlycerophosphocholinesGPCho (16:0/9Z,12Z-18:2)GPGPnChoGlycerophosphonocholinesGPGPEtnGlycerophosphoethanolaminesGPGPnEtnGlycerophosphonoethanolaminesGPGPSerGlycerophosphoserinesGPGPGroGlycerophosphoglycerolsGPGPGroPGlycerophosphoglycerophosphatesGPGPInsGlycerophosphoinositolsGPGPInsPGlycerophosphoinositol monophosphatesGPGPInsP2Glycerophosphoinositol bis-phosphatesGPGPInsP3Glycerophosphoinositol tris-phosphatesGPGPAGlycerophosphatesGPGPPGlyceropyrophosphatesGPCLGlycerophosphoglycerophosphoglycerolsGPCDP-DGCDP-glycerolsGP[glycan]GPGlycerophosphoglucose lipidsGP[glycan]GPInsGlycerophosphoinositolglycansEtN-P-6Manα1−2Manα1−6 Manα1−4GlcNα1-6GPIns (14:0/14:0)SPCerCeramidesCer (d18:1/9E-16:1)SPSMPhosphosphingolipidsSM (d18:1/24:0)SP[glycan]CerGlycosphingolipidsNeuAcα2−3Galβ1−4Glcβ-Cer (d18:1/16:0)GLMGMonoradyl glycerolsMG (16:0/0:0/0:0)GLDGDiradyl glycerolsDG (18:0/16:0/0:0)GLTGTriradyl glycerolsTG (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. Open table in a new tab The fatty acyl structure represents the major lipid building block of complex lipids and therefore is one of the most fundamental categories of biological lipids. The fatty acyl group in the fatty acids and conjugates class (Table 4) is characterized by a repeating series of methylene groups that impart hydrophobic character to this category of lipids. The first subclass includes the straight-chain saturated fatty acids containing a terminal carboxylic acid. It could also be considered the most reduced end product of the polyketide pathway. Variants of this structure have one or more methyl substituents and encompass quite complex branched-chain fatty acids, such as the mycolic acids. The longest chain in branched-chain fatty acids defines the chain length of these compounds. A considerable number of variations on this basic structure occur in all kingdoms of life (9Vance D.E. Vance J.E. Biochemistry of Lipids, Lipoproteins and Membranes. 4th edition. Elsevier Science, New York2002Google Scholar, 10Small D.M. Hanahan D.J. The Physical Chemistry of Lipids. Handbook of Lipid Research. 4. Plenum Press, New York1986Crossref Google Scholar, 11Brennan P.J. Nikaido H. The envelope of mycobacteria.Annu. Rev. Biochem. 1995; 64: 29-63Crossref PubMed Scopus (1548) Google Scholar, 12Ohlrogge J.B. Regulation of fatty acid synthesis.Annu. Rev. Plant Physiol. Plant Mol. Biol. 1997; 48: 109-136Crossref PubMed Scopus (521) Google Scholar), including fatty acids with one or more double bonds and even acetylenic (triple) bonds. Heteroatoms of oxygen, halogen, nitrogen, and sulfur are also linked to the carbon chains in specific subclasses. Cyclic fatty acids containing three to six carbon atoms as well as heterocyclic rings containing oxygen or nitrogen are found in nature. The cyclopentenyl fatty acids are an example of this latter subclass. The thia fatty acid subclass contains sulfur atom(s) in the fatty acid structure and is exemplified by lipoic acid and biotin. Thiols and thioethers are in this class, but the thioesters are placed in the ester class because of the involvement of these and similar esters in fatty acid metabolism and synthesis.TABLE 4Fatty acyls [FA] classes and subclassesFatty 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] Open table in a new tab Separate classes for more complex fatty acids with multiple functional groups (but nonbranched) are designated by the total number of carbon atoms found in the critical biosynthetic precursor. These include octadecanoids and lipids in the jasmonic acid pathway of plant hormone biosynthesis, even though jasmonic acids have lost some of their carbon atoms from the biochemical precursor, 12-oxo-phytodienoic acid (13Agrawal G.K. Tamogami S. Han O. Iwahasi H. Rakwal R. Rice octadecanoid pathway.Biochem. Biophys. Res. Commun. 2004; 317: 1-15Crossref PubMed Scopus (91) Google Scholar). Eicosanoids derived from arachidonic acid include prostaglandins, leukotrienes, and other structural derivatives (14Murphy R.C. Smith W.L. The eicosanoids: cyclooxygenase, lipoxygenase, and epoxygenase pathways.in: Vance D.E. Vance J.E. Biochemistry of Lipids, Lipoproteins and Membranes. 4th edition. Elsevier Science, New York2002: 341-371Google Scholar). The docosanoids contain 22 carbon atoms and derive from a common precursor, docosahexaenoic acid (15Bazan N.G. The metabolism of omega-3 polyunsaturated fatty acids in the eye: the possible role of docosahexaenoic acid and docosanoids in retinal physiology and ocular pathology.Prog. Clin. Biol. Res. 1989; 312: 95-112PubMed Google Scholar). Many members of these separate subclasses of more complex fatty acids have distinct biological activities. Other major lipid classes in the fatty acyl category include fatty acid esters such as wax monoesters and