Lippincots Ilustrated reviews Biochemistry Glucose Synthesis is Required for Survival Brain is dependent on glucose 120gday Body glucose reserve is limited 20 g extra cellular fluid ID: 1040896
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1. Gluconeogenesis Suggested Reading:Lippincot’s Ilustrated reviews: Biochemistry
2. Glucose Synthesis is Required for SurvivalBrain is dependent on glucose 120g/dayBody glucose reserve is limited≈ 20 g (extra cellular fluid)≈ 75 g ( liver glycogen); enough for 16 hours≈ 400 g (muscle glycogen); for muscle use onlyMain source of energy for resting muscle in postabsorptive state70 Kg man has ≈ 15 Kg fat Fatty acids can not be converted to glucoseUtilization of FA is increased 4-5 X in prolonged fastingIn prolonged fasting; FA ketone bodies at high rate
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4. Gluconeogenesis occurs mainly in the liverTissues that do not oxidize glc. completelye.g RBCsExercising muscleMuscle A.AcidsAdipose tissueLactatealanineglycerolGlucosePeripheral tissues
5. Entrance of substrates into gluconeogenesisLactate Pyruvate Amino acidsAmino acids oxaloacetate propionateGlycerol Triosephosphates FructoseGalactose Glucose
6. GlucoseGlucose 6-phosphateFructose 1,6- bisphosphate2 PhosphoenolpyruvateOxaloacetate2 PyruvateFructose 6-phosphate
7. Formation and Hydrolysis of Glucose 6-phosphate 1) Glc. + Pi Glc. 6-phosphate + H2O ΔG = +ve2) ATP + H2O ADP + Pi ΔG = -ve Glc. + ATP Glc. 6-phosphate + ADP ΔG = -ve Glc. 6-phosphate + H2O Glc. + Pi ΔG = -ve HKPhosphatase
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10. Carboxylation of Pyruvate Produces Oxaloacetate ADPATP>CO2
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12. GlucoseGlucose 6-phosphateFructose 1,6- bisphosphate2 PhosphoenolpyruvateOxaloacetate2 PyruvateFructose 6-phosphateATPGTPATPX 2X 2X 2
13. Regulation of Glycolysis and Gluconeogenesis
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17. Regulation by ATP and AMP; why AMPADP + ADP ATP + AMP
18. Regulation of PFK by Fructose 2,6- bisphosphateFruc. 6-phosphate + ATP Fruc. 2,6 bisphosphate + ADP
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22. GlucosePhosphenolpyruvateGlucose 6-PFructose 6-PFructose 1,6-bis-PPyruvateGlucagonInsulin-+GlucagonInsulin-+GlucagonInsulin-+GlucokinasePFKPK
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24. T2 ADP2 ATP
25. The Cori Cycle
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28. GlucosePhosphenolpyruvateGlucose 6-PFructose 6-PFructose 1,6-bis-PPyruvateGlucagonInsulin-+GlucagonInsulin-+GlucagonInsulin-+GlucokinasePFKPK
29. PFK
30. Pyruvate kinasePyruvate carboxylase
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34. Glycogen MetabolismSuggested Reading:Lippincott’s Ilustrated reviews: Biochemistry
35. Sources of Blood Glucose DietStarch, mono and disahccarides, glucose Sporadic, depend on diet, GluconeogenesisSustained synthesisSlow in responding to falling blood glucose levelGlycogen Storage form of glucoseRapid response and mobilization. Limited amountImportant energy source for exercising muscle.
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38. * Extensively branched homopolysaccharide* One molecule consists of hundreds of thousands of glucose units
39. Reducing endNonreducing end
40. Degradation of glycogen Degradation of glycogenOne glucose unit is removed at a timeFrom the nonreducing endsReleased in the form of glucose 1-phosphate
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42. Phosphate Ribose UracilGlycogen is synthesized by adding glucose one by oneUDP-Glucose s the active donor of glucose units
43. Formation of UDP-Glucose
44. Formation of UDP-Glucose Glucose-PPPPRibose-UracilGlucose-PPRibose-UracilPPPyrophosphate~~~~
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47. Glycogen Storage DiseasesGenetic diseases Defect in an enzyme required for synthesis or degradation Accumulation of excessive amount of glygcogenIn one or more tissueSeverity: FATAL in Infancy……. Mild disorder
48. Glycogen Storage Diseases (examples)I Glucose-6-phosphatase (von Gierk’s) diseaseLiver, kidney and intestine. Severe fasting hypoglycemiaHepatomegaly fatty liver.Normal glycogen structure.Progressive renal disease.Growth retardation.
49. Glucose 6+ Phosphatase Deficiency
50. Glycogen Storage Diseases (examples)V Muscle glycogen phosphorylase (McArdle syndrome)Only muscle is affected; Weakness and cramping of muscle after exercise no increase in [lactate] during exercise
51. Glycogen Storage Diseases (examples)II Lysosomes α (1→4) glucosidase POMP Disease Degradation of glycogen in the lysosomes≈ 3% of glycogen is degraded in the lysosomesAffects liver, heart and muscleExcessive glycogen in abnormal vacuoles in the lysosomesMassive cardiomegalyNormal blood sugar, normal glycogen structreEarly death from heart failure.
52. Pphosphogluco-mutase
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56. Energy needed for glycogen synthesisGlucose + ATP Glucose 6-phosphate + ADPGlucose 6-phosphate Glucose 1-phosphateGlucose 1-phosphate + UTP UDP-Glucose + PPi PPi + H2O 2PiUDP-Glucose + Glycogen(n) UDP + Glycogen(n+1)Glc. + ATP + UTP+Glycogen(n) ADP + UDP +Glycogen(n+1
57. The net reaction in glycogen synthesis and degradationGlucose 1-phosphate + UTP UDP-Glucose + PPi PPi + H2O 2PiUDP-Glucose + Glycogen(n) UDP + Glycogen(n+1)Glc. 1-phosph. + UTP+Glycogen(n) UDP +Glycogen(n+1 DegradationGlycogen(n) + Pi Glycogen(n-1) +Glc. 1-phosphate
58. PInhibitor proteinGlc
59. GLYCOGEN SYNTHESIS IS INHIBITEDcAMP dependent protein kinase APhosphorylation at several sitesInhibition is proportional to the degree of phosphorylation
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61. Allosteric RegulationRapid response to cell’s needsAvailable substate and ATP synthesis↓↓Glucose and ↓ATP Glycogenolysis
62. Ca2+-calmodulin activates dephosphorylated Phosphorylase kinase
63. Calcium Activation of liver phosphorylase Kinase
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67. Next TopicMetabolism of mono and disaccharides
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70. UracilRibosePhosphate
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