BBMB 405 1st Edition Lecture 6 Outline of Last Lecture I Chapter 20 The Calvin Cycle and the Pentose Phosphate Pathway A The pentose phosphate Pathway Generates NADPH and Synthesizes Five Carbon Sugars B The metabolism of Glucose 6 phosphate by pentose Phosphate pathway Is coordinated with glycolysis II Handout Outline of Current Lecture I Chapter 20 The Calvin Cycle and the Pentose Phosphate Pathway E Glucose 6 phosphate Dehydrogenase plays key role in protection against reactive oxygen species II Handouts III Chapter 21 Glycogen Metabolism A Glycogen Breakdown requires the interplay of several enzymes B Phosphorylase is regulated by allosteric interaction and reversible Current Lecture I Chapter 20 The Calvin Cycle and the Pentose Phosphate Pathway E Glucose 6 phosphate Dehydrogenase plays key role in protection against reactive oxygen species 1 Glucose 6 phosphate dehydrogenase deficiency causes a drug induced hemolytic anemia see handout 1 23 2 A deficiency of glucose 6 phophaste dehydrogenase confers an evolutionary advantage in some circumstances 2GSH ROOH Glutathione peroxidase GSSG H2O ROH These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute II Handout F Carl and Gerty Gori 1 Cori Cycle Muscle Liver Glycogen Glucose Glucose Glycogen Lactate Lactate 2 G 1 P Cori ester 3 Source of G 1 P was phosphorylase action on glycogen 4 AMP activation of phosphorylase 5 G 6 P G 1 P III Handout A Activation via Ca release into cytosol See handout B Regulation of glycogen degradation 1 Allosteric regulation a Muscle p 417 AMP activates phsophorylase b ATP replaces AMP thus inactivates b G 6 P inactivates b b Liver glucose inactivates phosphorylase a c Muscle and Liver Ca activates phopsphorylase kinase 2 Covalent modification cAMP mediated phosphorylation of phosphorylase kinase and phsophorylase C Reversal of activation of phosphorylase kinase and phosphorylase and inhibition of glycogen synthase 1 Hormone dissociates or is endocytosed 2 GTPase activity removes G protein activity 3 Phosphodiesterase action decreases cAMP 4 Protein phosphatase 1 PP1 dephosphorylates enzymes 5 Ca pumps cytosolic Ca into ER lumen IV Chapter 21 Glycogen Metabolism A Glycogen Breakdown requires the interplay of several enzymes 1 Most Prevalent organic polymer produced by living organism of earth a Cellulose 1015 kg yr b Chitin 1013 kg yr c Starch 1013 kg yr d World s production of glycogen 525 6 x 109 kg yr 2 Degradation and synthesis are reciprocally related one turned on other is turned of 3 Glycogen metabolism is regulated release and storage of glucose a Glycogen in liver regulates blood glucose level b Average is a branch for every 10 glucose units c Alpha 1 4 linkage between units of glucose and alpha 1 6 to make branches d Why store glucose as glycogen Need too much water to dissolve glucose and will weigh to much glycogen can be stored 1g glycogen to 2g water e Don t store glycogen in brain so it dies quickly if no oxygen supply f Fate of glucose 6 phosphate 4 Phosphorylase catalyzes phophorolytic cleavage of glycogen to release glucose 1 phosphate a Hydrolize the non reducing end of glycogen b First step in regulation c 5 Mechanism pyridoxal phosphate participates in phosphorolytic cleavage of glycogen a Active site of enzyme excludes water but not phosphate where the alpha 1 4 bond is broken b Can either use phosphoralation or hydrolysis the diference is one ATP one creates glucose with one ATP and the other without I believe hydrolysis makes glucose and phosphorylation makes glucose 6phosphate c Link between Lysine and PLP Schif base linkage 6 Debranching enzyme also is needed for breakdown of glycogen a b c Transferase removes 3 units of glucose and moves them to another branch d Alpha 1 6 Glucosidase bifunctioning enzyme see above catalyze hydrolysis of glucose 7 Phosphoglucomutase converts glucose 1 phosphate into glucose 6 phosphate 8 Liver contains glucose 6 phosphatase hydrolytic enzyme absent from muscle a Liver is poor at converting glucose to energy because it s primary function is to make glucose for other tissues b Glucose 6 phosphatase transport glucose to exterior c Muscle cannot export glucose d Glucose 6 phosphate H2O glucose Pi e Reaction above is catalyzed by G 6 phosphatase a membrane associated enzyme B Phosphorylase is regulated by allosteric interaction and reversible 1 Muscle phosphorylase is regulated by intracellular energy charge a Diferent conformations change the activity of phsophosylase R and a more active b ATP and AMP work together in active muscle c Liver glucose is major allosteric regulator not controlled by AMP which is more constant in liver d More glucose turns of phosphorylase activity phosphorylates glucose in liver e 2 Liver phosphorylase produces glucose for use by other tissues a Role of glycogen degradation in liver is to form glucose for export to other tissues when blood glucose concentration is low b If glucose in diet not need for degrade glycogen 3 Phosphorylase kinase is activated by phosphorylation and calcium ions a Subunits of Phosphorylase kinase alpha regulatory beta phosphorylated gamma catalytic phosphorylated phosphorylase delta calcium modulated protein calmodulin bind Ca