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.