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Carbohydrate Metabolism: Gluconeogenesis

INTER 111: Graduate Biochemistry. Carbohydrate Metabolism: Gluconeogenesis. Carbohydrate metabolism upon fasting. ‘average’ 8 hr sleep. ‘average’ 12 hour fast. Gluconeogenesis is also major component of normal metabolism - in sleep, 35-70% blood glucose supplied by gluconeogenesis.

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Carbohydrate Metabolism: Gluconeogenesis

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  1. INTER 111: Graduate Biochemistry Carbohydrate Metabolism:Gluconeogenesis

  2. Carbohydrate metabolism upon fasting ‘average’ 8 hr sleep ‘average’ 12 hour fast Gluconeogenesis is also major component of normal metabolism - in sleep, 35-70% blood glucose supplied by gluconeogenesis

  3. PEPCK is thought to be essential in glucose homeostasis, as evidenced by laboratory mice that contracted diabetes mellitus type 2 as a result of the overexpression of PEPCK. Burgess et al. (2007) Cytosolicphosphenolpyuvatecarboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver. Cell Metabolism 5(4), 313-320.

  4. Mighty mice: PEPCK expressed in skeletal muscle

  5. INTER 111: Graduate Biochemistry Carbohydrate Metabolism:Glycogen

  6. glycogen Chemical structure of glycogen Branched chain homopolysaccharide, exclusively made of a-D-glucose

  7. Electron micrograph of liver cell shows glycogen deposits in the cytosol

  8. Main stores of glycogen are skeletal muscle and liver Formation and breakdown of glycogen occurs in the cytosol Muscle glycogen – fuel reserve for ATP synthesis duringmuscle contraction Liver glycogen - maintain blood glucose concentration 400 g glycogen ~1-2% fresh weight of resting muscle 100 g glycogen ~ 10% adult liver

  9. Glycogen formation = glycogenesis Glycogen breakdown = glycogenolysis Metabolic pathways involving glycogen

  10. UDP-glucose synthesis is the first step in glycogenesis

  11. A primer is necessary to initiate glycogen synthesis glycogenin glycogen synthase Glycogen synthase makes a(1->4) linkages in glycogen

  12. Glycogen synthase elongates glycogen chains glycogenin glycogen synthase

  13. Glycogen has branches ~every 8 glucosyl units apart a(16) bond Branching enzyme [amylo-a(1->4)-a(1->6)-transglucosidase] transfers a chain of 5-8 glucosyl units from a nonreducing glycogen end and attaching it by an a(1->6) linkage.

  14. Glycogen has branches ~every 8 glucosyl units apart further elongation at the nonreducing ends by glycogen synthase further branching GLYCOGEN

  15. Initial step in glycogenolysis is chain shortening at the nonreducing ends Pi Glycogenphosphorylase Glucose 1-P

  16. Branches are removed by two enzymatic activities of a single bifunctional protein Oligo-a(1->4)-a(1->4)glucantransferaseremoves outer 3 of the 4 glucosyl units on a branch & transfers them to the nonreducing end of another chain

  17. A second type of debranching enzyme participates in removing a(1 6) bonds The remaining single glucose residue attached in ana(1->6)linkage is removed by amylo-a(1->6)-glucosidase.

  18. Glu 1-P from glycogen phosphorylase is converted to glu 6-P

  19. Concept map for glycogen metabolism in the liver

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