FIGURE 5.

GAGosome model. A, in the WT liver cell both NDST1 and NDST2 are expressed. NDST1 is preferred as GAGosome component leaving NDST2 outside the functional enzyme complex. Because NDST2^−/− cells and WT cells both have identical NDST1-containing GAGosomes, they synthesize HS with identical structure (21). A few of the GAGosomes in NDST1^−/− cells contain NDST2 and synthesize a low sulfated HS. B, in the heparin/HS biosynthesis machinery of WT MCs, NDST2 is the dominating NDST isoform, but a few GAGosomes contain NDST1. In the NDST2^−/− cells, only the remaining NDST1-containing GAGosomes can modify the heparin/HS chains, and a low sulfated product is synthesized. When NDST1 is lacking, all GAGosomes contain NDST2, and a polysaccharide with a sulfate content exceeding that of heparin produced by WT MCs is produced.