Gags And Enzymatic Reactions

Unlike the production of DNA, RNA or proteins, glycan synthesis does not depend on a template that codes for the exact order of building blocks in a new chain, to be faith-fully replicated over and over again as an exact copy. Instead, GAGs are produced through the concerted action of a large repertoire of enzymes whose existence and relative actions vary greatly. In short, HSGAG biosynthesis is a multi-step sequence with several enzyme players.
Several of the enzymes involved in HSGAG biosynthesis are now identified, but exactly how the process of production plays out is still very much an open question. Little is known about the effect of enzymes or, even more basically, whether they work independently or co-operatively in a multi-enzyme complex.
It is known that HSGAGs are produced inside the cell in the membranes of the organelles known as the Golgi apparatus. Nearly all the enzymes involved with making HSGAGs either span the organelle’s membranes or are at least peripherally associated with them. This arrangement essentially restricts the action of these enzymes to two dimensions within a lipid lattice.
Although the full biochemical picture is not yet known, it is likely that the enzymes for HSGAG biosynthesis come together inside the Golgi membrane, perhaps as the chain is being assembled.
For the most part, glycans do not exist at the cellular surface or in the extracellular matrix (ECM) as free-standing polymers. Rather, they are assembled onto certain proteins to form protein-glycan compounds, or proteoglycans. With the exception of heparin, which is created as a free-standing sugar compound, HSGAGs are commonly found in three major classes of proteoglycans.
Structure Determines Function
Proteoglycans are unique and structurally intricate macromolecules. A hint to the function of HSGAG proteoglycans comes from the list of important proteins with which they link in delicate spatial and temporal interactions.
These proteins have many key growth factors and growth-factor receptors, proteins participating in cellular and organ development, others participating in defensive and inflammatory reactions, some that regulate cell adhesion, and so on. Like proteoglycans, the proteins that associate with them generally are outside cells, either near cellular membranes or dispersed throughout the ECM. Many of these proteins are in the blood, where they are involved in mechanisms like blood coagulation, wound healing and tissue repair.
The interactions between glycans and the proteins they link too reveal connections between composition and activity. These interactions have often been ascribed simply to the noncovalent electrostatic attraction between negatively charged sugars and positively charged proteins. A better look, however, shows that many protein-glycan interactions are in fact structurally selective.