Regulation of sialic acid O-acetylation in human colon mucosa.
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.
Shen
Yanqin
Y
Biochemisches Institut, Christian-Albrechts-Universität zu Kiel, Olshausenstr. 40, D-24098 Kiel, Germany.
Tiralongo
Joe
J
Kohla
Guido
G
Schauer
Roland
R
D000105:Acetyl Coenzyme A / Q000037:antagonists & inhibitors / Q000378:metabolism; D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D001212:Asialoglycoproteins / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D003106:Colon / Q000737:chemistry / Q000378:metabolism*; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D060748:Fetuins; D006001:Glycoconjugates / Q000737:chemistry / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009077:Mucins / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D012799:Sialyltransferases / Q000378:metabolism; D013363:Submandibular Gland / Q000737:chemistry; D022161:Transport Vesicles / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D001212:Asialoglycoproteins; D060748:Fetuins; D006001:Glycoconjugates; D008562:Membrane Glycoproteins; D009077:Mucins; D000509:alpha-Fetoproteins; C017029:asialofetuin; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; C018766:N-acylneuraminate-9(7)-O-acetyltransferase; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase