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Chunk #13 — Biosynthesis of DS

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Biological functions of iduronic acid in chondroitin/dermatan sulfate.
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The products of DS-epi1 and 2 are difficult to assess as a result of the complex interaction with D4ST1. DS-epi1 can generate long blocks of IdoA together with D4ST1 (Fig. 3). Down-regulation of D4ST1 resulted in the abrogation of IdoA-containing blocks without affecting overall epimerase activity 24. The role of DS-epi2 has been more difficult to assess. Overexpression of DS-epi2 increased IdoA in hybrid structures (Fig. 3). No increase of IdoA blocks was recorded upon overexpression of DS-epi2, whereas overexpression of DS-epi1 resulted in enhanced block formation 16. By contrast, down-regulation of DS-epi2 in fibroblasts decreased the proportion of IdoA blocks, although to a smaller degree than that obtained by down-regulation of DS-epi1. Data obtained from DS-epi1 knockout mice show that DS-epi2 mainly forms alternating structures 28. These data indicate that DS-epi2 might be primarily involved in the formation of isolated or alternating IdoA structures (Fig. 3).