UDP-Xyl is primarily synthesized by UDP-GlcA decarboxylase (UGlcA-DC, also named UDP-Xylose Synthase, Uxs) from UDP-GlcA. The enzyme has a tightly bound NAD+, which participates first in the oxidation of UDP-GlcA to the UDP-4ketohexose intermediate resulting in decarboxylation (removal of COOH as gas, CO2) and formation of UDP — 4ketopentose. In the second stage, the NADH-bound enzyme reduces the UDP-4ketopentose to UDP-Xyl resulting in the release of NAD-bound enzyme (403). Multiple distinct UXS isoforms encoding this enzyme activity were reported in Arabidopsis (431), rice (474), barley (475), and tobacco (463). Uxs isoforms are very specific enzymes and act only on UDP-GlcA. The 4-epimer of UDP-GlcA, UDP-GalA is not a substrate for Uxs (431). Uxs is active as a dimer and inhibited by UDP-Xyl. In plants, UDP-Xyl is made in the cytosol and in the endomembrane system (473). Phylogeny analysis classified the six Uxs isoforms from Arabidopsis into three distinct clades: Type A (1 isoform, At3g53520); Type B (2 isoforms, At3g62830, At2g47650), and Type C (3 isoforms, at5g59290, At3g46440, At2g28760). Type A and B isoforms have an N-terminal extension (~ 120 aa long) which encodes longer proteins compared to Type C Uxs isoforms. Type A and B UXS isoforms are predicted Type II membrane proteins with the catalytic domain facing the endomembrane lumen (431). Expression of Type B Uxs isoforms in plants confirmed that Uxs2 is an integral membrane protein. Expressing of a Uxs2-GFP construct in tobacco leaves was shown to localize the chimeric fusion protein in the Golgi apparatus (473). Uxs3 belongs to the Type C clade and the isoform was found in the cytosol as predicted.