DEFECTIVE GALACTOSYLATION OF SERUM TRANSFERRIN IN GALACTOSEMIA

The glycosylation of serum transferrin from galactosemic patients with a deficiency of galactose-1-phosphate uridyl transferase (EC 2.7.7 12 ) is abnormal but becomes normal after treatment with a galactose-free diet, To understand the structural and biochemical basis of the abnor mal glycosylation, transferrin was purified from the serum of untreate d and treated galactosemic patients and normal controls and the N-link ed glycans analyzed by HPLC. The glycans from normal transferrin consi sted predominantly (86 %) of the disialylated biantennary complex type . The glycans from untreated galactosemic patients were more heterogen eous and contained four major truncated glycans in addition to a small er amount (13 %) of the disialylated biantennary complex type, The tru ncated glycans mere deficient in galactose and sialic acid and their s tructures were consistent with a decrease in galactosyltransferase act ivity in hepatocytes, the probable cells of origin of the transferrin, This is postulated to be due to direct inhibition of the galactosyltr ansferase activity by the accumulated galactose-1-phosphate or to an e ffect on the formation of UDP-galactose, the donor substrate in the re action. After treatment the proportion of the truncated glycans decrea sed and the proportion of the disialylated biantennary complex type in creased, returning almost but never completely to normal, even after p rolonged treatment in some cases, There was no clear relationship betw een the length of treatment and the normalization of glycosylation and the level of galactose-l-phosphate in red blood cells, the usual para meter for monitoring the treatment of galactosemics, It is suggested t hat the persistence of abnormally glycosylated proteins may contribute to the long-term complications in galactosemia.