MBBS Glycogen Synthesis and Degradation 2023 PDF

MBBS Stage one Nutrition and Metabolism Glycogen synthesis and degradation Despo Papachristodoulou  questions How much glycogen do we eat every day? Why the oyster in my first slide? Why do marathon runners eat a lot of CHO for days before a race? GLYCOGEN SYNTH...

MBBS Stage one Nutrition and Metabolism Glycogen synthesis and degradation Despo Papachristodoulou  questions How much glycogen do we eat every day? Why the oyster in my first slide? Why do marathon runners eat a lot of CHO for days before a race? GLYCOGEN SYNTHESIS AND REGULATION Outcomes:  Outline the important features of the structure of glycogen;  Indicate the importance of liver glycogen in maintaining constant levels of glucose in the blood;  Indicate the importance of muscle glycogen as a rapid source of glucose for muscle contraction;  Describe the enzyme reactions for the conversion of glucose to glycogen, emphasising the importance of glycogen synthetase;  Describe the enzyme reactions for the breakdown of glycogen, emphasising the importance of glycogen phosphorylase;  Briefly indicate the control mechanisms which regulate the activity of these two key enzymes.  ROLE OF GLYCOGEN IN LIVER GLUCOSE HOMEOSTASIS 100 – 120 g The liver is sensitive to blood glucose concentration It acts to maintain blood glucose under the control of insulin and glucagon GLYCOGEN IN MUSCLE FUEL FOR EXERCISE 250 – 300g The muscle is sensitive to energy needs of the tissue It is sensitive to adrenaline, calcium, AMP, ATP Glycogen has a branched structure. Physiological significance? TERMINAL RESIDUES -1,6 links -1,4 glycoside links ‘REDUCING END’ OF POLYMER TWO TYPES OF LINKAGES IN GLYCOGEN FEATURES OF BIOSYNTHETIC PATHWAYS ATP or UTP or GTP are needed as cofactors (to ‘drive the reactions forward’) one or more enzyme reactions will be irreversible, and alternative enzymes are used for the ‘opposite direction’ enzyme reactions at the beginning or end of the pathway are tightly regulated Makes sense? FIRST STAGES OF DIET GLYCOGEN SYNTHESIS FROM GLUCOSE FORMATION OF UDP GLUCOSE GLUCOSE-1-P + UTP transferase PPi + UDP glucose ADDITION OF GLUCOSE UNIT TO PROTEIN PRIMER PROTEIN glycogen synthase PRIMER (GLYCOGENIN) And the action continues  BRANCH POINTS are introduced into the structure of glycogen SITE OF ACTION OF BRANCHING ENZYME  GLYCOGEN SYNTHASE AND BRANCHING ENZYME PRODUCE THE BRANCHED STRUCTURE OF GLYCOGEN Glycogen synthase enzyme extends the straight chains approx 8-10 branching units enzyme introduces site for new chains How is glycogen synthase regulated? BY PHOSPHORYLATION Regulation of glycogen synthase PROTEIN KINASE + ATP  REGULATION OF GLYCOGEN SYNTHASE Pi PROTEIN PROTEIN PHOSPHATASE KINASE GLYCOGEN BREAKDOWN  SITES OF PHOSPHORYLASE ACTION REMAINING SHORT BRANCHES AFTER PHOSPHORYLASE ACTION  removal of glucose units from branched regions requires 1,6 glycoside link hydrolysed by debranching enzyme straight chain regions degraded further by glycogen phosphorylase acting on 1,4 links Release of free glucose glycogen breakdown by phosphorylase results in the production of glucose-1- phosphate glucose- 1-P mutase enzyme glucose-6-P glucose -6- phosphatase (liver only) glucose Blood stream  REGULATION OF GLYCOGEN PHOSPHORYLASE protein protein phosphatase kinase Figure 05.06 ATP Pi ATP Pi adrenaline + glucagon + insulin adrenaline + glucagon + insulin  Additional controls: liver The liver responds to insulin/glucagon When glucose is high it binds to the glycogen phosphorylase and inactivates it.  Muscle During muscular contraction, Calcium ions are released into the sarcoplasmic reticulum. Calcium binds the calmodulin domain of glycogen phosphorylase kinase and activates the enzyme This in turn activates the phosphorylase and glycogen is degraded providing energy for contracting muscle  In addition, In prolonged exercise, ATP concentrations are reduced and AMP concentrations begin to rise. AMP is an allosteric activator of glycogen phosphorylase. Glycogen degradation continues without the need for hormonal interaction ATP is an allosteric inhibitor, so that when energy levels are high, glycogen breakdown stops