留学生-糖代谢.ppt

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * A sugar nucleotide is formed through a condensation reaction between a NTP and a sugar phosphate. The suitability of sugar nucleotides for biosynthetic reactions stems from several properties: 1.Their formation is metabolically irreversible, contributing to the irreversibility of the synthetic pathways in which they are intermediates. (PPi is rapidly hydrolyzed) 2.The nucleotide moiety has many groups that can undergo noncovalent interactions with enzymes. The additional free energy of binding can contribute significantly to catalytic activity. 3. Like phosphate, the nucleotidyl group (UMP or AMP, for example) is an excellent leaving group, facilitating nucleophilic attack by activating the sugar carbon to which it is attached. 4. By “tagging” some hexoses with nucleotidyl groups, cells can set them aside in a pool for one purpose (glycogen synthesis, for example), separate from hexose phosphates destined for another purpose (such as glycolysis). Tissues: Liver, Muscles The starting point for synthesis of glycogen is glucose 6-phosphate. Glucose 6-phosphate + ADP Glucose + ATP HK (GK) To initiate glycogen synthesis, the glucose 6- phosphate is converted to glucose 1-phosphate in the phosphoglucomutase reaction: Glucose 6-phosphate glucose 1-phosphate Glucose 1-phosphate is converted to UDP-glucose by the action of UDP-glucose pyrophosphorylase, in a key step of glycogen biosynthesis: Glucose 1-phosphate + UTP UDP-glucose + PPi Glycogen is synthesized using UDP-glucose Glycogen synthase catalyzes transfer of the glucose residue of UDP-Glucose to the hydroxyl at C4 of the nonreducing end of a glycogen chain (of at least 4 glucose residues) to make a new a-1,4 glycosidic bond . Glycogen (n) + UDP-glucose Glycogen (n+1) + UDP Glycogen synthesis. The formation of (a1?6) branches of glycogen is catalyzed by glycogen-branching enzyme : a terminal fragment of 6-7 residues is tra