Intern:Lipids in PANGAEA

=Definition= Lipids constitute one of the four major classes of compounds found in living tissues (the others being carbohydrates, proteins, and nucleic acids) and they include: (1) fatty acids; (2) neutral fats (i.e. triacylglycerols), other fatty acid esters, and soaps; (3) long-chain (or fatty) alcohols and waxes; (4) sphingoids and other long-chain bases; (5) glycolipids, phospholipids, and sphingolipids; and (6) carotenes, polyprenols, sterols (and related compounds), terpenes, and other isoprenoids. (...)" (Oxford Dictionary of Biochemistry and Molecular Biology (2000), p.379)

=Use of abbreviations and retained names= Many lipids are big and complex molecules. To faciliate the handling of names, most scientists use retained names an specialised nomenclature and/or encrypt structural information in abbreviations. Moreover lipids are divided into several building blocks (especially for glycerolipids/triglycerides) and lipid families.

The following disadvantages occur for systematic names:

Systematic IUPAC names can become very complex and unwieldy. Moreover common lipid building blocks are less recognizable in systematic names (e.g. the glycerol backbone becomes propane-1,2,3-triol or propane-1,2,3-triyl respectively)

Many generic lipid structures can not be properly represented by classical systematic names. Due to IUPAC seniority rules and more complicated rules for stereochemistry, small changes of the molecular structure can change the whole name massively. Assigment of generic names for generic structures is not always possible with substitutive nomenclature (prefered nomenclature by IUPAC).

For an overview on common encoding abbreviations, see table 1 of this publication. Please note that usage of abbreviations can differ for specific lipid groups and always check the corresponding PANGAEA guidelines.

=Resolution of lipid identification= For general information on analysis techniques, read the Wikipedia article on Lipidomics.

tbc: mass spectrometry and output (eventually comparison to other techniques, which are not high throughput). Up to which level can be identified?

MS resolution levels (more info in material and methods, section 1)):

Level 1 (MS1): Only type of lipid (e.g. PC) and number of carbons and double bonds in total is known (--> e.g. PC 36:2), no structural information

Level 2 (MS2): Fatty acid carbons and double bonds are known, but not the sn-position or structure of the fatty acid (PC 16∶0_18∶1)

Level 3 (MS2) with intensity interpretation): Fatty acid position is known (PC 18∶1/16∶0)

Level 4: Double bond positions of fatty acid known(PC 18∶1 [9]/16∶0)

Level 4 can rarely be achieved, only by specialized laboratories. Unfortunately many scientists deduce detailed structural info from only knowing m/z values (m/z can only infer level 1 information)

Workflow of HPLC-MS-MS /ESI-MS analyses: Lipid extraction --> HPLC (seperates different lipid classes) --> ESI --> Mass Spectrometry 1 (=seperation by m/z) values) --> Mass Spectrometry 2 (fragmentation of the molecule and detection of fragments: identification of groups)

(see also: link1, )

Some analysis methods leave aways the LC-stept and directly transfer a crude extract to the ESI.

=Lipid systematics and nomenclature=

IUPAC nomenclature

 * Carotenoid nomenclature (1974) (PDF version)
 * IUPAC nomenclature on lipids (1976) (fatty acids and alcohols, glycerolipids, glycerophospholipids and old glycolipid rules)
 * Update: Derivatives of phosphatidic acid (1980)
 * Prenol nomenclature (1986) (PDF version)
 * Steroid nomenclature (1989) (PDF version)
 * Updated glycolypid nomenclature (1997) (PDF version)
 * Natural products and related compounds (1999) (including alkaloids, steroids, terpenes, carotenes, tetrapyrroles)
 * Chapter P-107 Lipids in IUPAC 2013 (p.1431 ff.) - a summary of past nomenclatures on lipids (excluding steroids), no added value.
 * Chapter P-101 Nomenclature of natural products in IUPAC 2013 (p.1294 ff.) - a summary of rules for several natural product groups (including alkaloids, steroids, terpenes, carotenes, tetrapyrroles)


 * Nomenclatures of "fat-soluble" vitamins (A, D, E, K)

Lipid Maps ontology and nomenclature
Lipids can be subdivided into several classes. The Lipid Maps database has developed the first internationally accepted Lipid Classification System with 8 categories (containing classes and subclasses):
 * Fatty Acyls [FA]
 * Glycerolipids [GL]
 * Glycerophospholipids [GP]
 * Sphingolipids [SP]
 * Sterol lipids [ST]
 * Prenol lipids [PR]
 * Saccharolipids [SL]
 * Polyketides [PK]

Statement of Lipid Maps for the construction of categories: "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." (source)

The maximum depth of the lipid hierarchy is four (in most of the cases three). The subclasses devide lipids by further characteristics besides the backbone (e.g. headgroup type and sidechain composition for glycerolipids and glycerophospholipids).

The LipidMaps nomenclature has extended the IUPAC nomenclature on lipids, which is already very old (1976: fatty acids and glycerolipids, later added: glycolipids, prenols and steroids) and does not cover all recently discovered lipid classes. However, glycolipids (containing sugar residues in their head groups) have not received a seperate category within the Lipid Maps Classification System. Because the system rather focuses on the lipid backbone, the glycolipids are dispersed across the 8 different categories.

Publications on the Lipid Maps Classification System: Initial, Update

Basic information on the lipid classes can be found in the lipid maps tutorial.

Shorthand notation by Liebisch et al.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646453/ A good overview about the lipid hierarchy based on structural information content can be found here.

=Glycerolipids= Glycerolipids are also called triglycerides. The common feature of all glycerolipids is the glycerol backbone.

Building blocks
Glycerol / Glycerine (prefix: glycero- or less commonly glyceryl-)

Diacyl

Dialkyl

DG /DAG = diacylglycerol

PE = phosphatidylenthanolamine or (sometimes wrongly used for phosphoethanolamine)

PC = phosphatidylcholine (sometimes wrongly used for phosphocholine)

Naming ambiguities and precautions

 * Prefix "phosphatidyl" can stand for glycerophospholipids with radyl chains (acyl, alkyl or 1-alkenyl) or only with acyl-chains. According to IUPAC, phosphatidyl only stands for acyl-substituted glycerophospholipids. (see also here)

Bonding types
tbc: 'O-' for alkyl and 'P-' for plasmalogen type bond acyl, alkyl and 1Z-alkenyl sidechains and the resulting bonding types

stereospecific numbering (sn-) nomenclature
Information: https://de.wikipedia.org/wiki/Sn-Nomenklatur (only German) https://en.wikipedia.org/wiki/Glycerophospholipid#Nomenclature_and_stereochemistry

Families of glycerolipids
=Information resources and databases=

Educational material
Lipid maps tutorials

Lipid Web

Lipid Library webpage

Cyberlipid (Search for specific lipids)

LipidomicNet Wiki

Powerpoint presentation on Intact Polar Lipids (concept, structure, classification, massspectrometry analyses basics)

Lipid Maps Structure Database
The Lipid Maps Structure Database (LMSD)is seen as the standard reference database for lipidomics.

SwissLipids
The SwissLipids database is developed by the Swiss-Prot, which is also responsible for the non-redundant UniProtKB/Swiss-Prot database. The SwissLipid database:
 * is manually curated
 * contains lipids with evidence as well as possible, in silico generated lipid structures
 * classifies lipids based on the Lipid Maps Ontology
 * generates abbreviations and offers additional ontological information until isomeric subspecies level using the notation scheme of Liebisch et al.
 * maps all hierarchy levels to ChEBI

Publication

LipidHome
The LipidHome database is a database for in silico generated, theoratically possible lipid structures. The LipidHome database:
 * covers only glycerolipids and glycerophospholipids
 * does not contain systematic names
 * focusses strongly on mass spectrometry data
 * uses the LipidomicNetstandard lipid nomenclature of Liebisch et al.
 * uses the structure representation rules of ChEBI

Publication

LipidBank
Lipid Bank (Wiki)

Other databases
Discontinued:

Lipidat

Lipid drawing tools
Lipid maps offers drawing tools for all lipid classes, which dramatically speed up the structure drawing process.

The corresponding backbone molecules are predefined and only the substituent information (number of carbons, double bonds, specific funtional groups, stereochemistry etc.) must be added.

Identifiers such as InChI-keys can not be directly obtained. For this purpose, download either the MDL MOL file or the SDF file and open them in a drawing tool such as BIOVIA:


 * MDL MOL file
 * Directly opened in BIOVIA
 * Use the Text-to-Structure Function to generate InChI-Strings/-keys and IUPAC names
 * Enantiomers included:
 * Textbox "AND Enantiomers" encodes for racemic mixtures (included in IUPAC name). Delete textbox if only depicted molecule is of interest.
 * Please note, that InChI can not encode for mixtures. Only depicted molecule is translated.
 * Molecule can be adapted in BIOVIA
 * SDF file
 * Opens SD Viewer Box
 * Automatical additional information: IUPAC name, InChIkey, Systematic name (lipid nomenclature name)
 * Please note, that InChI can not encode for mixtures. Only depicted molecule is translated.
 * No adaptions possible!