Regulation of sialic acid O-acetylation in human colon mucosa

Biol Chem. 2004 Feb;385(2):145-52. doi: 10.1515/BC.2004.033.

Abstract

The expression of O-acetylated sialic acids in human colonic mucins is developmentally regulated, and a reduction of O-acetylation has been found to be associated with the early stages of colorectal cancer. Despite this, however, little is known about the enzymatic process of sialic acid O-acetylation in human colonic mucosa. Recently, we have reported on a human colon sialate-7(9)-O-acetyltransferase capable of incorporating acetyl groups into sialic acids at the nucleotide-sugar level [Shen et al., Biol. Chem. 383 (2002), 307-317]. In this report, we show that the CMP-N-acetyl-neuraminic acid (CMP-Neu5Ac) and acetyl-CoA (AcCoA) transporters are critical components for the O-acetylation of CMP-Neu5Ac in Golgi lumen, with specific inhibition of either transporter leading to a reduction in the formation of CMP-5-N-acetyl-9-O-acetyl-neuraminic acid (CMP-Neu5,9Ac2). Moreover, the finding that 5-N-acetyl-9-O-acetyl-neuraminic acid (Neu5,9Ac2 could be transferred from neo-synthesised CMP-Neu5,9Ac2 to endogenous glycoproteins in the same Golgi vesicles, together with the observation that asialofetuin and asialo-human colon mucin are much better acceptors for Neu5,9Ac2 than asialo-bovine submandibular gland mucin, suggests that a sialyltransferase exists that preferentially utilises CMP-Neu5,9Ac2 as the donor substrate, transferring Neu5,9Ac2 to terminal Galbeta1,3(4)R- residues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl Coenzyme A / antagonists & inhibitors
  • Acetyl Coenzyme A / metabolism
  • Acetylation
  • Acetyltransferases / metabolism
  • Animals
  • Asialoglycoproteins / chemistry
  • Asialoglycoproteins / metabolism
  • Cattle
  • Colon / chemistry
  • Colon / metabolism*
  • Cytidine Monophosphate N-Acetylneuraminic Acid / analogs & derivatives
  • Cytidine Monophosphate N-Acetylneuraminic Acid / antagonists & inhibitors
  • Cytidine Monophosphate N-Acetylneuraminic Acid / metabolism*
  • Fetuins
  • Glycoconjugates / chemistry
  • Glycoconjugates / metabolism
  • Golgi Apparatus / metabolism
  • Golgi Apparatus / ultrastructure
  • Humans
  • Intestinal Mucosa / metabolism*
  • Membrane Glycoproteins / metabolism
  • Mucins / chemistry
  • Mucins / metabolism
  • Protein Transport
  • Rats
  • Sialyltransferases / metabolism
  • Submandibular Gland / chemistry
  • Transport Vesicles / metabolism
  • alpha-Fetoproteins / metabolism

Substances

  • Asialoglycoproteins
  • Fetuins
  • Glycoconjugates
  • Membrane Glycoproteins
  • Mucins
  • alpha-Fetoproteins
  • asialofetuin
  • Cytidine Monophosphate N-Acetylneuraminic Acid
  • Acetyl Coenzyme A
  • Acetyltransferases
  • N-acylneuraminate-9(7)-O-acetyltransferase
  • Sialyltransferases
  • beta-D-galactoside alpha 2-6-sialyltransferase