Regulation of sialic acid O-acetylation in human colon mucosa

The expression of Oacetylated sialic acids in human colonic mucins is developmentally regulated, and a reduction of Oacetylation 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 Oacetylation in human colonic mucosa. Recently, we have reported on a human colon sialate 7(9)Oacetyltransferase capable of incorporating acetyl groups into sialic acids at the nucleotidesugar level [Shen et al., Biol. Chem. 383 (2002), 307317]. In this report, we show that the CMPNacetylneuraminic acid (CMPNeu5Ac) and acetylCoA (AcCoA) transporters are critical components for the Oacetylation of CMPNeu5Ac in Golgi lumen, with specific inhibition of either transporter leading to a reduction in the formation of CMP-5-Nacetyl-9-Oacetylneuraminic acid (CMPNeu5,9Ac(2)). Moreover, the finding that 5-Nacetyl-9-Oacetylneuraminic acid (Neu5,9Ac(2)) could be transferred from neosynthesised CMPNeu5,9Ac(2) to endogenous glycoproteins in the same Golgi vesicles, together with the observation that asialofetuin and asialohuman colon mucin are much better acceptors for Neu5,9Ac(2) than asialobovine submandibular gland mucin, suggests that a sialyltransferase exists that preferentially utilises CMPNeu5,9Ac(2) as the donor substrate, transferring Neu5,9Ac(2) to terminal Galbeta1,3(4)R residues.