Lipid classification, structures and tools

Abstract

The study of lipids has developed into a research field of increasing importance as their multiple biological roles in cell biology, physiology and pathology are becoming better understood. The Lipid Metabolites and Pathways Strategy (LIPID MAPS) consortium is actively involved in an integrated approach for the detection, quantitation and pathway reconstruction of lipids and related genes and proteins at a systems-biology level. A key component of this approach is a bioinformatics infrastructure involving a clearly defined classification of lipids, a state-of-the-art database system for molecular species and experimental data and a suite of user-friendly tools to assist lipidomics researchers. Herein, we discuss a number of recent developments by the LIPID MAPS bioinformatics core in pursuit of these objectives.

Fig. 1

Lipid building blocks. The LIPID MAPS classification system is based on the concept of 2 fundamental biosynthetic “building blocks”: ketoacyl groups and isoprene groups.

Fig. 2

Mechanisms of lipid biosynthesis. Biosynthesis of ketoacyl- and isoprene-containing lipids proceeds by carbanion and carbocation-mediated chain extension, respectively.

Fig. 3

Examples of lipid categories. Representative structures from each of the 8 LIPID MAPS lipid categories.

Fig. 4

Lipid structure representation. Examples of structures from a number lipid categories in which acyl or prenyl chains are oriented horizontally with the terminal functional group (in green) on the right and the unsubstituted “tail” on the left.

Fig. 5

Structural similarity of PC and SM. Orientation of examples of phosphatidylcholine (PC) and sphingomeyelin (SM) structures highlights their similarity. The sphingosine “backbone” of SM is biosynthetically derived from palmitoyl-CoA (green) and serine (red) whereas PC contains a glycerol core (red) with an additional acyl chain (green). Both molecules contain a phosphocholine (pink) headgroup.

Fig. 6

Searching the LIPID MAPS structure database. A selection of screen shots showing various options for searching LIPID MAPS Structure Database (LMSD).

Fig. 7

Use of InchIKeys in lipid structure searching. The first 14 characters of the InChIKey main layer (in red) define the molecular formula and bond connectivity of the molecule. In the case of cholic acid, searching the database with “BHQCQFFYRZLCQQ” will retrieve all 16 bile acid stereoisomers corresponding to the 3 hydroxyl groups and C5 stereocenter.

Fig. 8

Overview of LIPID MAPS structure data generation methodology. A set of MOLfile templates are used as a starting point for the lipid structure drawing programs which in turn programmatically manipulate these molfiles to extend radyl chains and/or add various functional groups. The drawing programs are capable of accepting input either from online forms on the LIPID MAPS website or from lists of abbreviations in command-line mode.

Fig. 9

LIPID MAPS structure drawing tools. A selection of screen shots showing the online structure drawing tools and options on the LIPID MAPS website.

Fig. 10

LIPID MAPS MS prediction tools. Some screen shots showing the online MS prediction tools on the LIPID MAPS website. Several options are available for defining both the search parameters and output format. Results are linked to isotopic distribution profiles and discrete structures (where applicable).