Effect of orotic acid on beta 1,4-galactosyltransferase during liver regeneration.

Abstract

The study was designed to understand the effect of orotic acid (OA) on the expression of beta 1,4-galactosyltransferase (GalTase), an enzyme involved in the transfer of galactose from UDP-galactose to a non-reducing terminal N-acetylglucosamine of a glycoprotein or glycolipid. Rats were fed a semisynthetic diet containing 1% OA for 2 weeks and the livers were stimulated to regenerate by two-thirds partial hepatectomy (PH). The level of activity of the enzyme and the steady-state level of hepatic mRNA transcripts of GalTase were determined prior to PH and at 12, 24, 48, 72 h and 10 days after the surgery. The data show that the hepatic activity of GalTase is unaltered in both the control and OA-fed groups until 12 h following surgery, but begins to increase after this time period. In the control group a progressive increase was seen throughout the experimental period following PH. On the other hand in the OA-fed group 24 h after PH the initial increase seen up to 24 h was arrested later on and the activity remained inhibited throughout the rest of the experimental period. The supplementation of 1% OA diet with 0.3% adenine, which is known to reverse the OA-induced imbalance in the nucleotide pool sizes, relieved the inhibition of GalTase activity. The steady-state level of hepatic mRNA paralleled the activity of GalTase at all the time points studied during liver regeneration. The reduction in the level of mRNA transcripts of GalTase in the OA-fed group may not be due to either a general inhibition of synthesis and/or degradation of mRNAs as revealed by a comparison of the expression of beta-galactoside 2,6-sialyltransferase in both the control and OA-fed groups. The study thus suggests an imbalance in nucleotide pools, such as the one induced by OA, may play a role in the regulation of glycosylation by modulating the glycosyltransferases.