Glycogen Metabolism Part 3 PDF

METABOLISMO DE GLÚCIDOS: PARTE 3 M 1  GLYCOGEN METABOLISM GLYCOGEN IS AN ENERGY SOURCE STORED MAINLY IN THE LIVER AND MUSCLE GLUCOSE RESIDUES ARE REMOVED FROM GLYCOGEN BY GLYCOGEN PHOSPHORYLASE ✓ This...

METABOLISMO DE GLÚCIDOS: PARTE 3 M 1  GLYCOGEN METABOLISM GLYCOGEN IS AN ENERGY SOURCE STORED MAINLY IN THE LIVER AND MUSCLE GLUCOSE RESIDUES ARE REMOVED FROM GLYCOGEN BY GLYCOGEN PHOSPHORYLASE ✓ This process is repetitive; the enzyme removes successive glucose residues until it reaches the fourth glucose unit from a branch point M 2  GLYCOGEN METABOLISM Dealing with Branch Points in Glycogen 1. Glycogen phosphorylase works on non-reducing ends until it reaches four residues from an (1→ 6) branch point 2. Debranching enzyme transfers a block of three residues to the non- reducing end of the chain 3. Debranching enzyme cleaves the single remaining (1→6)–linked glucose Glucose 1-phosphate is then transformed into Glucose 6-phosphate by phosphoglucomutase enzyme. HYDROLYSYS OF GLUCOSE 6-PHOSPHATE GLUCOSE-6-PHOSPHATE IS DEPHOSPHORYLATED IN THE LIVER FOR TRANSPORT OUT OF THE LIVER M 3  CONTROL OF GLYCOGEN BREAKDOWN EPINEPHRINE AND GLUCAGON STIMULATE BREAKDOWN OF GLYCOGEN Glucagon/Epinephrine signaling pathway Starts phosphorylation cascade via cAMP Activates glycogen phosphorylase Glycogen phosphorylase cleaves glucose residues off glycogen, generating glucose-1-phosphate M 4  SYNTHESIS OF GLYCOGEN GLYCOGENIN STARTS A NEW GLYCOGEN CHAIN Glycogenin catalyzes two distinct reactions. Initial attack by the hydroxyl group of Tyr194 on C-1 of the glucosyl moiety of UDP-glucose results in a glucosylated Tyr residue. The C-1 of another UDP-glucose molecule is now attacked by the C- 4 hydroxyl group of the terminal glucose, and this sequence repeats to form a nascent glycogen molecule of eight glucose residues attached by (14) glycosidic linkages. M 5  SYNTHESIS OF GLYCOGEN GLYCOGEN IS SYNTHESIZED BY GLYCOGEN SYNTHASE UDP-GLUCOSE IS THE SUBSTRATE FOR GLYCOGEN SYNTHASE UDP-GLUCOSE IS SYNTHETIZED FROM GLUCOSE-1-PHOSPHATE AND URIDINE TRIPHOSPHATE (UTP) BY UDP-GLUCOSE PYROPHOSPHATASE M 6  SYNTHESIS OF GLYCOGEN GLYCOGEN IS SYNTHESIZED BY GLYCOGEN SYNTHASE A glycogen chain is elongated by glycogen synthase. The enzyme transfers the glucose residue of UDP-glucose to the nonreducing end of a glycogen branch to make a new (α14) linkage. M 7  SYNTHESIS OF GLYCOGEN SYNTHESIS OF BRANCHES IN GLYCOGEN The glycogen-branching enzyme (also called amylo (14) to (16) transglycosylase, or glycosyl-(46) transferase) forms a new branch point during glycogen synthesis. M 8  CONTROL OF GLYCOGEN SYNTHESIS Insulin-signaling pathway increases glucose import into muscle stimulates the activity of muscle hexokinase activates glycogen synthase Increased hexokinase activity enables activation of glucose Glycogen synthase makes glycogen for energy storage M 9  CONTROL OF GLYCOGEN SYNTHESIS Insulin-signaling pathway ✓ increases glucose import into muscle ✓ stimulates the activity of muscle hexokinase ✓ activates glycogen synthase Increased hexokinase activity enables activation of glucose Glycogen synthase makes glycogen for energy storage M 10  CONTROL OF GLYCOGEN SYNTHESIS Insulin-signaling pathway ✓ increases glucose import into muscle ✓ stimulates the activity of muscle hexokinase ✓ activates glycogen synthase Increased hexokinase activity enables activation of glucose Glycogen synthase makes glycogen for energy storage M 11  REGULATION OF PHOSPHOFRUCTOKINASE-1 Catalyses the commitment step in glycolysis While ATP is a substrate, ATP is also a negative effector Do not spend glucose in glycolysis if there is plenty of ATP EFFECT OF ATP ON PHOSPHOFRUCTOKINASE-1 M 12  REGULATION OF PHOSPHOFRUCTOKINASE 1 AND FRUCTOSE 1,6-BISPHOSPHATASE Go glycolysis if AMP is high and ATP is low Go gluconeogenesis if AMP is low M 13  FRUCTOSE 2,6-BISPHOSPHATE F-2,6-BP is produced from fructose-6-phosphate NOT a glycolytic intermediate, only a regulator Produced specifically to regulate glycolysis and gluconeogenesis activates phosphofructokinase (glycolysis) inhibits fructose 1,6-bisphosphatase (gluconeogenesis) M 14  REGULATION OF F-2,6-BP LEVELS Glucólisis PFK-1 activada Gluconeogénesis inhibida FBPasa-1 Glucólisis inhibida PFK-1 Gluconeogénesis activada FBPasa-1 M 15  Glycolysis and gluconeogenesis are differentially regulated by F-2,6-BP M 16  Regulation of Pyruvate Kinase Pyruvate kinase M 17  REGULATION OF PYRUVATE KINASE Pyruvate kinase M 18  REGULATION OF PYRUVATE KINASE Pyruvate kinase M 19  REGULATION OF PYRUVATE KINASE M 20  TWO ALTERNATIVE FATES FOR PYRUVATE Pyruvate can be a source of new glucose ✓ Store energy as glycogen ✓ Generate NADPH via pentose phosphate pathway Pyruvate can be a source of acetyl-CoA ✓ Store energy as body fat ✓ Make ATP via citric acid cycle Acetyl-CoA stimulates glucose synthesis by activating pyruvate carboxylase M 21  THE AMOUNT OF MANY METABOLIC ENZYMES IS CONTROLLED BY TRANSCRIPTION M 22  CONTROL OF CARBOHYDRATE METABOLISM IN THE LIVER M 23  CONTROL OF CARBOHYDRATE METABOLISM IN THE LIVER VS. THE MUSCLE M 24