Two
lysosomal storage diseases,
aspartylglucosaminuria and
mannosidosis, are associated with highly elevated serum
dolichol concentrations. To elucidate possible mechanisms leading to elevated serum
dolichols, we studied the effects of
Triton WR 1339 (known to increase serum
cholesterol) and
orotic acid (known to decrease serum
cholesterol) on blood and biliary
dolichol and
beta-hexosaminidase levels in rats. In Triton WR 1339-treated rats, serum
dolichol was markedly increased compared with saline-treated controls 1 (400 +/- 70 ng/mL, n = 7 v 85 +/- 11 ng/mL, n = 8, P < .001), 4 (789 +/- 70 ng/mL, n = 10 v 110 +/- 10 ng/mL, n = 7, P < .0001), and 8 (549 +/- 43 ng/mL, n = 8 v 87 +/- 8 ng/mL, n = 7, P < .001) days after administration of the
drug. By contrast, serum
dolichol was decreased (64 +/- 5 ng/mL, n = 8 v 119 +/- 7 ng/mL, n = 8, P < .0001) after a 7-day
orotic acid feeding compared with controls. Serum
beta-hexosaminidase was unaffected by both treatments.
Orotic acid also increased biliary
dolichol (280 +/- 47 ng/100 g
body weight [BW]/h, n = 7 v 83 +/- 15 ng/100 g BW/h, n = 7, P < .01) and
beta-hexosaminidase (21 +/- 3 mU/100 g BW/h, n = 7 v 8.3 +/- 2 mU/100 g BW/h, n = 9, P < .01) excretion compared with controls. Thus, both
Triton WR 1339 and
orotic acid have an effect on
dolichol metabolism, and it is conceivable--based on our results--that serum
dolichol concentrations are regulated, at least in part, by a mechanism similar to that for serum
cholesterol levels.