Lipid classification, nomenclature and structure drawing

The LIPID MAPS consortium has developed a comprehensive classification, nomenclature, and chemical representation system for lipids, the details of which are are described in the May 2009 issue of the Journal of Lipid Research:

• Fahy E, Subramaniam S, Murphy R, Nishijima M, Raetz C, Shimizu T, Spener F, van Meer G, Wakelam M and Dennis E.A.,Update of the LIPID MAPS comprehensive classification system for lipids. J. Lipid Res. (2009) 50: S9-S14.PubMed ID:19098281.
• Fahy E, Subramaniam S, Brown H, Glass C, Merrill JA, Murphy R, Raetz C, Russell D, Seyama Y, Shaw W, Shimizu T, Spener F, van Meer G, Vannieuwenhze M, White S, Witztum J and Dennis E.A.,A comprehensive classification system for lipids. J. Lipid Res. (2005) 46: 839-861.PubMed ID:15722563.

The LIPID MAPS Lipid Classification System is comprised of eight lipid categories, each with its own sublassification hierarchy. All lipids in the LIPID MAPS Structure Database (LMSD) have been classified using this system and have been assigned LIPID MAPS ID's (LM_ID) which reflects their position in the classification hierarchy. Starting from a lipid category, the user can navigate through the hierarchy by clicking on the "[+]" icon next to a main class name. This will expand that item to reveal its sub classes. Clicking on hyperlinks to the right of main classes, sub classes or level 4 classes will display a tabular listing of all lipids corresponding to that particular subset in the LMSD database. Finally, clicking on the LM_ID hyperlink displays the LMSD record for an individual lipid, wich contains an image of the molecular structure, common and systematic names, links to external databases, Wikipedia pages (where available), other annotations and links to structure viewing tools.

Hierarchy

• Category (Example: Prenol lipids [LMPR])
    Main class (Example: Isoprenoids [LMPR01])
      Sub class (where applicable) (Example: C15 Isoprenoids (sesquiterpenes) [LMPR0103])
        Level 4 class (where applicable) (Example: Bisabolane sesquiterpenoids [LMPR010306])
  

The LIPID MAPS LM_ID identifier

The LIPID MAPS ID (LM_ID) is a unique identifier based on the classification scheme described above. The format of the LM_ID, outlined in the table below, 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. Currently, most LM_ID's have 12 characters, the exceptions being the molecules belonging to the level-4 classes of prenol lipids which have LM_ID's of 14 characters. The last four characters of the LM_ID comprise a unique identifier within a particular subset and are randomly assigned. In the case of generic structures containing "R" groups (such as 1,2-diacyl-sn-glycero-3-phosphocholine) the last 4 characters are all zeros (e.g. LMGP01010000). One other item worthy of note is that for most of the Glycosphingolipid 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 2 digits of the LIPID MAPS LM_ID identifier are assigned as "00" to signify an unspecified N-acyl side-chain, and the 3rd and 4th last digits are given a different 2-letter identifier for every unique glycan chain within that subclass. For example, in the Gangliosides subclass ([LMSP0601]) the GM1 generic structure is assigned an LM_ID of LMSP0601AP00 where the "AP" digits specify the unique NeuAca2-3Galβ1-3(NeuAca2-6)GalNAcβ1-3Galα1-4Galβ1-4Glcβ glycan chain and the terminal "00" digits indicate a generic ceramide structure.

Depositing new lipid structures in the LMSD and assigning LM_ID's

The Bioinformatics core of the LIPID MAPS Consortium has responsibility for registration of new lipid structures and assignment of LM_ID identifiers. Individuals who wish to deposit novel structures in the LIPID MAPS structure database (LMSD) may do so via a Web-based registration system on the web site. This enables users to enter lipid structures and accompanying names, synonyms, references, and classification information. During the submission process, structures are validated for uniqueness using a search on the current database. The submitted structures are stored in a private, temporary database where they are reviewed by LIPID MAPS bioinformatics staff prior to being classified, checked for correct nomenclature, and registered in the public LMSD.
Questions regarding the submission of structures should be submitted via our Contact page.

LIPID MAPS LM_ID format

LIPID MAPS abbreviations for glycerophospholipids

LIPID MAPS abbreviations for glycerolipids

LIPID MAPS abbreviations for sphingolipids

Large and complex lipids are difficult to draw, which leads to the use of short hand and unique formats that often generate more confusion than clarity among lipidologists. We propose a more consistent format for representing lipid structures where, in the simplest case of the fatty acyl derivatives, the acid group (or equivalent) is drawn on the right and the hydrophobic hydrocarbon chain is on the left (see Fig. 1). Notable exceptions are found in the eicosanoid class where 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 hand side. In addition, the linear prenol lipids are drawn in a fashion analogous to the fatty acids with the terminal functional group on the right hand side. Sterol lipids are universally drawn with the A ring at bottom-left and the 5-membered D ring at top-right. 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.
Many classes of lipids lend themselves well as targets for automated structure-drawing, due to their consistent 2-dimensional layout. A suite of structure-drawing tools has been developed and deployed which permit in-silico generation of structures, systematic names and abbreviations. 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 section of the LIPID MAPS website. Examples of structures for the 8 lipid categories are shown in the figure below.