BBMB 405 1st Edition Lecture 6Outline of Last Lecture I. Chapter 20: The Calvin Cycle and the Pentose Phosphate PathwayA. The pentose phosphate Pathway Generates NADPH and Synthesizes Five-Carbon SugarsB. The metabolism of Glucose 6-phosphate by pentose Phosphate pathway Is coordinated with glycolysisII. HandoutOutline of Current Lecture I. Chapter 20: The Calvin Cycle and the Pentose Phosphate PathwayE. Glucose 6-phosphate Dehydrogenase plays key role in protection against reactive oxygen speciesII. HandoutsIII. Chapter 21: Glycogen MetabolismA. Glycogen Breakdown requires the interplay of several enzymesB. Phosphorylase is regulated by allosteric interaction and reversibleCurrent LectureI. Chapter 20: The Calvin Cycle and the Pentose Phosphate PathwayE. Glucose 6-phosphate Dehydrogenase plays key role in protection against reactiveoxygen species1. 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 + ROHThese 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 Gori1. Cori Cycle Muscle LiverGlycogen Glucose  Glucose  Glycogen Lactate  Lactate2. G-1-P Cori ester3. Source of G-1-P was phosphorylase action on glycogen4. AMP activation of phosphorylase5. G-6-P  G-1-PIII. Handout A. Activation via Ca++ release into cytosol (See handout)B. Regulation of glycogen degradation1. Allosteric regulationa. Muscle (p. 417): AMP activates phsophorylase b, ATP replaces AMP; thus inactivates b, G-6-P inactivates bb. Liver: glucose inactivates phosphorylase ac. Muscle and Liver: Ca++ activates phopsphorylase kinase2. Covalent modification: cAMP-mediated phosphorylation of phosphorylase kinase and phsophorylaseC. Reversal of activation of phosphorylase kinase and phosphorylase and inhibition of glycogen synthase1. Hormone dissociates or is endocytosed2. GTPase activity removes G protein activity3. Phosphodiesterase action decreases [cAMP]4. Protein phosphatase 1 (PP1) dephosphorylates enzymes5. Ca pumps cytosolic Ca++ into ER lumenIV. Chapter 21: Glycogen MetabolismA. Glycogen Breakdown requires the interplay of several enzymes1. Most Prevalent organic polymer produced by living organism of earth?a. Cellulose: 1015 kg/yrb. Chitin: 1013 kg/yrc. Starch: <1013 kg/yrd. World’s production of glycogen: 525.6 x 109 kg/yr2. Degradation and synthesis are reciprocally related: one turned on other is turned of3. Glycogen metabolism is regulated release and storage of glucosea. Glycogen in liver regulates blood glucose levelb. Average is a branch for every 10 glucose unitsc. Alpha 1,4 linkage between units of glucose and alpha 1,6 to make branchesd. 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 watere. Don’t store glycogen in brain so it dies quickly if no oxygen supplyf. Fate of glucose 6-phosphate4. Phosphorylase catalyzes phophorolytic cleavage of glycogen to release glucose 1-phosphatea. Hydrolize the non reducing end of glycogenb. First step in regulationc.5. Mechanism: pyridoxal phosphate participates in phosphorolytic cleavage of glycogena. Active site of enzyme excludes water but not phosphate, where the alpha-1,4 bond is brokenb. 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 6-phosphate)c. Link between Lysine and PLP: Schif-base linkage6. Debranching enzyme also is needed for breakdown of glycogena.b.c. Transferase: removes 3 units of glucose and moves them to another branchd. Alpha-1,6 Glucosidase: bifunctioning enzyme (see above), catalyze hydrolysis of glucose7. Phosphoglucomutase converts glucose 1-phosphate into glucose 6-phosphate8. Liver contains glucose 6-phosphatase, hydrolytic enzyme absent from musclea. Liver is poor at converting glucose to energy because it’s primary functionis to make glucose for other tissuesb. Glucose 6-phosphatase transport glucose to exteriorc. Muscle cannot export glucosed. Glucose 6-phosphate + H2O  glucose + Pie. Reaction above is catalyzed by G-6-phosphatase, a membrane associated enzymeB. Phosphorylase is regulated by allosteric interaction and reversible1. Muscle phosphorylase is regulated by intracellular energy chargea. Diferent conformations change the activity of phsophosylase: R and a more activeb. ATP and AMP work together in active musclec. Liver: [glucose] is major allosteric regulator, not controlled by AMP which is more constant in liverd. More glucose turns of phosphorylase activity, phosphorylates glucose in livere.2. Liver phosphorylase produces glucose for use by other tissuesa. Role of glycogen degradation in liver is to form glucose for export to othertissues when blood-glucose concentration is lowb. If glucose in diet, not need for degrade glycogen3. Phosphorylase kinase is activated by phosphorylation and calcium ionsa. Subunits of Phosphorylase kinase: alpha (regulatory), beta (phosphorylated), gamma (catalytic, phosphorylated phosphorylase), delta (calcium modulated protein- calmodulin, bind