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.