The epimerase reaction is reversible, with an equilibrium of 9 : 1 (GlcA to IdoA) under in vitro conditions when the biosynthetic complex has been solubilized with detergent 4. On the other hand, CS/DS chains in vivo can contain a higher proportion of IdoA. This is assumed to be achieved through functional collaboration between DS-epi1 and D4ST1 (Fig. 3) 23. In support of this, transient down-regulation of D4ST1 results in a reduced IdoA content 24. Genetic mutations in D4ST1 found in a new type of Ehlers–Danlos syndrome (i.e. adducted thumb-clubfoot syndrome) also result in CS/DS of low IdoA content 25.
