Dissertation (Metadaten)
Titel:Sialate-O-Acetylation and De-O-Acetylation in Human Colonic Mucosa
Autor:Yanqin Shen
Fakultät:Mathematisch-Naturwissenschaftliche Fakultät
DDC Sachgebiet:610 Medizin und Gesundheit
Datum der mdl. Prüfung:28.06.2002
Referent(in):Prof. Dr. Roland Schauer
Korreferent(en) Korreferentin:Prof. Dr. Holger Kalthoff
Beschreibung:Sialic acids are a family of nine-carbon based on neuraminic acid. O-Acetylation at C-7,8,9 positions of sialic acids is one of the most common modifications, which is catalyzed by acetyl coenzyme A:sialate-7(9)-O-acetyltransferase(7(9)-OAT; EC levels of O-acetylated N-acetylneuraminic acid are expressed in human colonic mucosa, and the decrease in these levels are proposed to be related to colorectal cancer metastasis. However, little is known about the enzymatic process of sialate O-acetylation in human colonic tissue. In this study, human coloic 7(9)-OAT was found to be distinct from other reported OATs, for it utilizes CMP-Neu5Ac instead of sialoglycoproteins and gangliosides as the acceptor substrate. The nature of enzyme product, CMP-Neu5,9Ac2 was confirmed via chromatographic and enzymatic methods. The enzyme is facing the lumenal side of Golgi membranes, and the enzyme activity shows the dependence on the concentrations of substrates, membrane integrity, and the temperature as well as pH. Moreover, a sialyltransferase showing the preference for CMP-Neu5,9Ac2 as sialate donor and human colonic mucins as acceptor substrate is proposed to be involved in the expression of O-acetylated sialic acids on human colonic mucins. The data shown here, together with the previous investigations suggest the existence of a family of 7(9)-OATs with different acceptor substrate preferences. Using a group of 12 matched tissue pairs(the histologically normal and cancerous tissues from the same patient), it is found that the decrease in the activity of 7(9)-OAT is one reason for the reduced amount of O-acetylated sialic acids in human colorectal cancer.
Schlagworte:sialic acid , sialate-O-acetyltransferase, colonic mucosa, human , O-acetylation , colorectal cancer, sialate-O-acetylesterase
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