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Lipids: Definitions, Classification and Nomenclature


Definitions

Although most of us who work with these fascinating molecules have our own understanding of what is meant by the term "lipid", there is no agreement in the lipid community over the definition. The following comments represent my personal view therefore. The historical origins of the term make interesting reading, and should assist with a definition [1]. It has evolved via ‘lipine’, ‘lipin’, ‘lipoid’ and ‘lipide’ and was originally used in a more restricted sense. Thus, Bloor [2] in 1920 classified lipoids into three groups, simple lipoids (fats and waxes), compound lipoids (phospholipoids and glycolipoids) and derived lipoids (fatty acids, alcohols and sterols). This classification appeals to me and appears to have been accepted until the 1950s. Only later and rather arbitrarily were compounds such as carotenoids, terpenes, steroidal hormones and now polyketides included in the term.

Scottish thistleGeneral text books tend to describe lipids in woolly terms as a group of naturally occurring compounds, which have in common a ready solubility in such organic solvents as hydrocarbons, chloroform, benzene, ethers and alcohols. They comprise a diverse range of compounds that can encompass fatty acids and their derivatives, carotenoids, terpenes, steroids and bile acids. It should be apparent that many of these compounds have little by way of structure to relate them, although they may have certain functions in common. In fact, a definition of this kind is positively misleading, since many of the substances that are now widely regarded as lipids, for example gangliosides and bile acid conjugates, may be as soluble in water as in organic solvents. Unfortunately, this definition persists in the scientific literature and respected text books [3].

Such indeterminate descriptions are understandable when it is recognized that there is no definition of a lipid that has been accepted by any international body that recommends standards or comments on nomenclature issues. In particular, IUPAC-IUB appear to have shirked the task. Where others fear to tread, I put forward my own preferred definition in 1987 [4], and I recommend it until something better is proposed. It is -

Lipids are fatty acids and their derivatives, and substances related biosynthetically or functionally to these compounds.

This encompasses all the compounds we consider to be the mainstream of lipids, together with those hydrophobic compounds that function in membranes, e.g. sterols, the fat-soluble vitamins, and some but not necessarily all isoprenoids and polyketides.

A further useful guide to lipid classification, structures and nomenclature is a paper by Fahy and colleagues [5], which is available from the Journal of Lipid Research as a free download here.... It is complemented by a website – Lipid Maps®, which in addition to defining lipids, catalogues and illustrates a great number of them and makes available drawing and other tools as a service to aid lipid scientists. I applaud their attempt to define the term 'lipid', though their definition still seems too broad to me, i.e.

Lipids are 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.).

This definition may make sense to a biochemist, but what are physical chemists, food scientists and so forth to make of it? For example, non-biochemists may find it difficult to reconcile most polyketides with their view of the more traditional lipids. It has even been argued that this definition appears to suggest that almost any organic compound not a carbohydrate, protein or nucleic acid is a lipid. While this may be a perfectly valid view-point, it would make my task as a chronicler of lipid science much more difficult. One answer to this conundrum might be to define 'lipids' as I have done above (or something close to it - I am always amenable to suggestions), and then resurrect an older term such as 'lipoid' or 'lipide' for lipids in the widest sense, such as those encompassed by the Lipid Maps® definition.

Lipid versus non-lipid?


Classification of Lipid Structures

cartoon scientistFahy and colleagues [5] of the Lipid Maps® consortium also made an interesting attempt to classify lipid structures in a manner that facilitated cataloguing by computer. I expressed a number of reservations when this paper was first published and subsequently directly to the authors and indirectly via my blogs, mainly because the document seemed to be heavily weighted towards animal lipids, while many unique and important plant lipids had been overlooked. This fault was largely remedied in a second publication [6], where the authors generously admitted their earlier bias and introduce new sub-classifications to encompass the plant glycosyldiacylglycerols including a key lipid in photosynthesis - sulfoquinovosyldiacylglycerols (although lower in their hierarchy than the glycerophospholipids). Sterols are now categorized according to their chemical structures rather than to their biological origins.

That said, my own preference would be to elevate more of the sub-classes to a higher level for functional reasons. For example, the glycosyldiacylglycerols have similar physical properties and functions in plant membranes as the glycerophospholipids, and they should be classified in the same rank. I would have three analogous classes for sphingolipids, with perhaps a fourth for gangliosides, as to be consistent, phospho-sphingolipids and glyco-sphingolipids should be treated separately by analogy with the glycerolipid classifications. Similarly, in the fatty acyl group, I would elevate eicosanoids/docosanoids to a higher rank for functional reasons, and it appears to me anomalous to leave fatty alcohols and related wax constituents in this group. Another group in a classification limbo are the phosphoglycolipids (as defined here).

The general aims of the two papers are admirable, and hopefully what I consider the faults will be cured in time by dialogue. Lipid Maps® is of course a private consortium, not an international standards body, although I expect that their proposals will be given serious consideration by IUPAC-IUB and other international commissions in due course.

I would also argue that a subdivision of glycerolipids into two broad classes according to polarity or complexity is so convenient for analysts, biochemists and physical chemists that it should be given greater weight in any practical classification system, i.e. those defined in the first edition of Lipid Analysis [7].

‘Simple lipids’ are those that yield on hydrolysis at most two types of primary products per mole; ‘complex lipids’ yield three or more primary hydrolysis products per mole.

This definition has echoes of Bloor’s "simple and compound lipoids". In practice, it is often necessary to subdivide the main groups further. For example, the complex lipids for many purposes are best considered in terms of either the glycerophospholipids (or simply as phospholipids), which contain a polar phosphorus moiety and a glycerol backbone, or the glycolipids, which contain a polar carbohydrate moiety. For practical reasons, sphingolipids are often analysed separately from the glycerolipids and they are usually treated by chemists and biochemists alike as a distinct group.

It can also be convenient to think in terms of storage lipids, e.g. triacylglycerols, versus structural lipids, i.e. those that occur and function in membranes such as most of the complex lipids, cholesterol and many of the fat-soluble vitamins.

Abbreviations: I have never been a fan of abbreviations; they are useful for authors but a nuisance for readers. If they must be used, it is better to decide on ones that are likely to become standards. Fahy et al. [5] initially suggested abbreviations that appeared to me to be needlessly complex for the main phospholipid classes, before in their 2009 paper [6] deciding to recommend the simpler two-letter forms in common use. As both formats now appear in publications, I list some of those most often encountered with the obsolete forms in brackets: phosphatidic acid - PA (GPA); phosphatidylcholine - PC (GPCho); phosphatidylethanolamine - PE (GPEtn); phosphatidylserines - PS (GPSer); phosphatidylinositol - PI (GPIns); phosphatidylinositol bis-phosphate - PIP2 (GPInsP2); phosphatidylglycerol - PG (GPGro); cardiolipin - CL; Cer - ceramides; TG - triacylglycerols; DG - diacylglycerols, MG - monoacylglycerols.


Nomenclature

The subjects of lipid nomenclature and classification are dealt with at many points in this website, but especially in relation to individual lipid classes as listed here. For definitive detailed accounts, we can serve you best by pointing to the following documents, which are all available in the form of PDF files as free downloads from the journals specified below.

Alternatively, the information is available from websites containing the IUPAC guide to the nomenclature of glycerolipids and fatty acids or to that for glyco-/sphingolipids. However, I have found discrepancies between the published and website versions for the former, especially in the shorthand nomenclature for fatty acids; the print versions are correct and definitive.


References

  1. Gidez, L.I. The lore of lipids. J. Lipid Res., 25, 1430-1436 (1984);  DOI.
  2. Bloor, W.R. Outline of a classification of the lipids. Proc. Soc. Exp. Biol. Med., 17, 138-140 (1920);  DOI.
  3. Gurr, M.I., Harwood, J.L., Frayn, K.N., Murphy, D.J. and Michell, R.H. Lipids: Biochemistry, Biotechnology and Health (6th Edition). (Wiley-Blackwell) (2016).
  4. Christie, W.W. High-performance liquid chromatography and Lipids: A Practical Guide (Pergamon Press, Oxford) (1987).
  5. Fahy, E. and 17 others. A comprehensive classification system for lipids. J. Lipid Res., 46, 839-862 (2005);  DOI - reprinted in Eur. J. Lipid Sci. Technol., 107, 337-364 (2005).
  6. Fahy, E. and 9 others. Update of the LIPID MAPS comprehensive classification system for lipids. J. Lipid Res., 50, S9-S14 (2009);  DOI.
  7. Christie, W.W. Lipid Analysis (1st edition) (Pergamon Press, Oxford) (1973).


Lipid listings Credits/disclaimer Updated: March 22nd, 2018 Author: William W. Christie LipidWeb icon