Glycosyltransferases are a class of enzymes that catalyse the posttranslational modification of proteins to produce a large number of glycoconjugate acceptors from a limited number of nucleotide-sugar donors. The products of one glycosyltransferase can be the substrates of several other enzymes, causing a combinatorial explosion in the number of possible glycan products. The kinetic behaviour of systems where multiple acceptor substrates compete for a single enzyme is presented, and the case in which high concentrations of an acceptor substrate are inhibitory as a result of abortive complex formation, is shown to result in non-Michaelian kinetics that can lead to bistability in an open system. A kinetic mechanism is proposed that is consistent with the available experimental evidence and provides a possible explanation for conflicting observations on the β-1,4-galactosyltransferases. Abrupt switching between steady states in networks of glycosyltransferase-catalysed reactions may account for the observed changes in glycosyl-epitopes in cancer cells.

O-linked glycosylation is an important post-translational modification of mucin-type protein, changes to which are important biomarkers of cancer. For this study of the enzymes of O-glycosylation, we developed a shorthand notation for representing GalNAc-linked oligosaccharides, a method for their graphical interpretation, and a pattern-matching algorithm that generates networks of enzyme-catalysed reactions. Software for generating glycans from the enzyme activities is presented, and is also available online. The degree distributions of the resulting enzyme-reaction networks were found to be Poisson in nature. Simple graph-theoretic measures were used to characterise the resulting reaction networks. From a study of in-silico single-enzyme knockouts of each of 25 enzymes known to be involved in mucin O-glycan biosynthesis, six of them, β-1,4-galactosyltransferase (β4Gal-T4), four glycosyltransferases and one sulfotransferase, play the dominant role in determining O-glycan heterogeneity. In the absence of β4Gal-T4, all Lewis X, sialyl-Lewis X, Lewis Y and Sda/Cad glycoforms were eliminated, in contrast to knockouts of the N-acetylglucosaminyltransferases, which did not affect the relative abundances of O-glycans expressing these epitopes. A set of 244 experimentally determined mucin-type O-glycans obtained from the literature was used to validate the method, which was able to predict up to 98% of the most common structures obtained from human and engineered CHO cell glycoforms.

Naming things is essential for people to understand one another, no matter what language or field of interest is involved. This is as true for enzymes, genes and chemicals as it is for birds, food, flowers, etc. Effective communication requires a lack of ambiguity, but, in practice, ambiguities abound even between people who use the same language in different parts of the world, or even within the same country. Whereas ambiguities in the words used for common objects or actions have been the basis for many, more-or-less memorable jokes, they can also cause a great deal of confusion. Such linguistic chaos is welcomed by many as being a part of a diverse heritage that should be preserved at all costs to prevent us from descending into Orwellian 'newspeak'. However, in the sciences, there are distinct advantages in others being able to understand what one is doing. Many groups have stressed the need for standardized, universally accepted systems of nomenclature in chemistry, genetics, enzymology, etc. However, it is the universal acceptance that usually causes the problem. It is rare to find people who will admit that they find nomenclature to be an interesting subject, but many who profess contempt for it will get very excited if it is suggested that their pet nomenclature should be changed in the interest of clarity or uniformity. This account will consider the development of the enzyme nomenclature system, its benefits, shortcomings and future prospects.