Glycosaminoglycans and proteoglycans

Nomenclature (including abbreviations and acronyms) of glycosaminoglycans (GAG) and proteoglycans (PG) is ad hoc.

Older terms such as chondroitin sulfates A, B, or C define major tissue components, but difficulties now occur as hybrid polymers from many tissues do not fit in this system; domain structures present in many tissue GAG are not recognised, and the spectra of modifications due to sulfation and 5-epimerisation of D-glucuronic acid (D-GlcA) provide no basis on which to distinguish between, for example, chondroitin and dermatan sulfates (CS and DS). If 10% iduronate (L-IdoA) qualifies chondroitin sulfate to be called dermatan sulfate, are chondroitin sulfate containing 9% iduronate and dermatan sulfate containing 11% iduronate different species?

It is proposed that terminology be based on disaccharide units, which are readily accessible to quantitative analysis, via enzymic digestion. These units are of unambiguous composition and can, for example, be represented by logical abbreviations.

Polymer abbreviations could be two-letter codes, e.g. CS, DS, HS (heparan sulfate), and KS (keratan sulfate). If there is no sulfation, Ch, De, Hp and Ke could be used. They are defined in terms of disaccharide units, thus Ch (chondroitan) is the disaccharide polymer [-4GlcA1-3GalNAc1-]_n, where GlcA is D-glucuronate and GalNAc is N-acetyl-D-galactosamine.

DS (currently an abbreviation for dermatan sulfate) consists of not only chondroitin sulfate disaccharides, containing D-glucuronate, but also its 5-epimer, L-iduronate. Probably all 'DS' contains chondroitin sulfate units. In order to avoid confusion about definitions of dermatan sulfate, which imply the complete epimerisation of D-GlcA to L-IdoA, the term 'dermochondan sulfate' is proposed, indicating that 'DS' preparations are co-polymeric. The abbreviation 'DS' could be retained for these polymers.

Keratan sulfate consists of repeating -3Gal1-4GlcNAc1- units, sulfated to various extents and in different positions. It belongs to the same polymer group as chondroitin sulfate.

Heparan sulfate is the sulfated polymer of heparan (Hp). Heparan consists of a polymer of the following two disaccharides: -4GlcA1-4GlcNAc1- and -4IdoA1-4GlcNAc1-. It is therefore analogous to dermochondan sulfate in containing two uronic-acid epimers. There are no names analogous to dermatan or chondroitin in this GAG family.

The abbreviation PG for proteoglycan is in wide use. A rational system should convey information about the protein and the glycan parts. Single names purporting to describe both are certain to confuse, since one part is a gene product and the other is introduced by a post-translational modification. They do not necessarily occur together. It is consistent to use proteochondroitan sulfate (PCS), proteokeratan sulfate (PKS), and now proteodermochondan sulfate (PDS) as abbreviations for proteoglycans with chondroitin sulfate, keratan sulfate or dermatan sulfate chains, respectively. If more than one type of glycosaminoglycan chain is attached to the protein, it is expressed, for example, as P(CS,KS) or P(CS,HS), the dominant GAG being written first. This convention can include quantitative or semi-quantitative information about the GAG, accommodating information on numbers of GAG chains attached to the protein, e.g. P(CS_70-100, KS_10-20, DS_7-10).

Protein cores may be viewed as gene products, as amino-acid sequences, as functioning units, or as characteristic shapes (sizes).

Names such as decorin, lumican, aggrecan, syndecan, etc. have been given over the past few years to molecules whose chemistry was known in detail. The names lack chemical information, are inconsistent and should only be used to name the direct gene product.

To emphasise their connection with the gene, rather than with the glycan, the ending 'on' (as in exon, intron, codon) could replace existing 'an', etc. Thus decoron, lumicon, aggrecon, syndecon. A proteoglycan is indicated by adding appropriate GAG abbreviations, e.g. decoron DS, lumicon KS, aggrecon CS,KS.

This complex area of biochemistry would benefit from a structured attempt to rationalise the nomenclature. Comments on the ideas presented here and other suggestions would be welcomed by the nomenclature committees and by John E. Scott (Department of Chemical Morphology, University of Manchester, Oxford Road, Manchester, England M13 9PL. Fax: +44 161 275-4598. E-mail: scott@fs1.ed.man.ac.uk). For references see [30-33].

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