The main interest of the Passi’s group is the glycosaminoglycan (GAG) metabolism with particular attention to hyaluronic acid. GAGs are linear sulphated polysaccharides containing uronic acid and hexosamine residues. These molecules are very common in nature and linked to a protein core constitute the proteoglycan family. Hyaluronan (HA) is a special GAG without core protein and completely unsulphated. The aim of our work is the study of the mechanisms driving the GAG synthesis. In order to achieve this target we use a biochemical approach integrated with molecular biology techniques and morphology. To address the GAG chemistry we set up a new electrophoretic method based on the carbohydrate fluorescence (FACE). This method is very simple, fast and able to detect few pmoles of samples. Our preliminary data indicate that over expression in cells of UGDH, the enzyme involved in the synthesis of UDP-glucuronic acid (UDPGlcUA), the UDP uronic precursors of all GAGs, induced an increase in the cells of this precursor and consequently an increase of HA synthesis. On the other hand the silencing of the same enzyme by siRNA induced in the cells the opposite effect, confirming that the availability of UDPGlcUA controls the HA synthesis. In order to quantify the UDP sugars precursors in the cells, we developed a method using HPLC able to separate and quantify all UDP sugars involved in GAG synthesis. Moreover, the altered UDP sugar concentration in the cells was able to alter the expression of the enzymes involved in the UDP sugars synthesis and even the enzymes involved in GAG synthesis. On this basis we are now elucidating the mechanisms involved in this control of enzymes of the pathway of GAG synthesis. For this purpose we also consider the post transcriptional modification of the enzymes using a proteomic approach based on bi-dimensional electrophoresis and mass spectrometry analysis coupled with a genomic approach base on the microarray chips and real time RT-PCR.