Glycogen Metabolism 2024 PDF

Glycogen Metabolism 2024 1 What is glycogen? Storage polysaccharide Where it is found? Mainly in the liver and muscles What is its function? In muscle: fuel tank for ATP during muscle contraction In liver: fuel tank for maintaining blood glucose concentration ? Differe...

Glycogen Metabolism 2024 1 What is glycogen? Storage polysaccharide Where it is found? Mainly in the liver and muscles What is its function? In muscle: fuel tank for ATP during muscle contraction In liver: fuel tank for maintaining blood glucose concentration ? Different functions 2  Synthesis of Glycogen (Glycogenesis) 1. Synthesis of UDP glucose 2. Synthesis of a primer to initiate glycogen synthesis 3. Elongation of glycogen chains by GLYCOGEN SYNTHASE 4. Formation of branches by Branching enzyme which is a 4,6 transferase Amylo-(14) (16)- transglucosidase 3 Degradation of Glycogen (glycogenolysis) A. Shortening of the chains By Glycogen phosphorylase – yielding G-1-P + a limit dextrin B. Removal of Branches By the debranching enzyme -2 enzymatic activities 4  Degradation of Glycogen ctd C: Conversion of G 1-P to G 6-P: by phosphoglucomutase D: Lysosomal Degradation: low constitutive level by (14)-glucosidase Deficiency- glycogen accumulates in vacuoles in lysosomes and results in GSD Type 11: Pompe disease 5 Enzyme deficiencies cause range of diseases called the glycogen storage diseases (GSD) Type 1(a) GSD Von Gierke Disease: glucose 6- phosphatase deficiency Type 1(b) GSD Glucose 6-phosphate translocase deficiency Type 11: Pompe Disease (lysosomal (14)- glucosidase deficiency Type 111: Cori Disease – debranching enzyme deficiency Type V: McArdle Syndrome –skeletal muscle glycogen phosphorylase deficiency Type VI: Hers disease – def of liver glycogen 6 phosphorylase Note: Pompe Disease – all organs with lysosomes involved Manifestations – infantile form – early-onset progressive muscle hypotonia, cardiac failure, death before age 2 7  Regulation of glycogenesis and glycogenolysis 1. Glycogen Synthase and Glycogen Phosphorylase are Hormonally regulated (by phos/dephos as on/off switches) 2. These enzymes are allosterically regulated 8 Hormone-mediated covalent regulation of glycogen metabolism 9  ISOZYMES Allosteric regulation of glycogen synthesis and degradation Glycogen Synthase and Glycogen phosphorylase responding to the energy needs of the cell Glycogenesis stimulated when ISOZYMES glucose and energy levels are high Glycogenolysis stimulated when glucose and energy levels are low 10 Stimulation and Inhibition of glycogen degradation –effect on glycogen phosphorylase 11 Hormonal Regulation of Glycogen Synthesis - effect on glycogen synthase 12 13 What you need to know at the end of this lecture What is glycogen? what is it for and where is it stored? What differentiates the functionality of glycogen stored in the liver and muscle? What are the key regulatory enzymes that synthesize and break down glycogen? What controls the activity of glycogen synthase and glycogen phosphorylase. How is glycogen metabolism linked to glycolysis? What is glycogenesis What are the GSDs? What are the underlying molecular defects of the main GSDs discussed in the lecture? What symptoms might a patient display who presents with a GSD Why can you consider that McArdle disease is a mere inconvience where Hers disease can be lethal? 14