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Glucagon Adrenaline glucagon adrenergic 2121 cAMP IP 3 DAG Ca 2+ PKC PKA inactive HormoneReceptorsubtype 2 nd messenger GG Gs Gi Gq GLUCAGON AND.

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Presentation on theme: "Glucagon Adrenaline glucagon adrenergic 2121 cAMP IP 3 DAG Ca 2+ PKC PKA inactive HormoneReceptorsubtype 2 nd messenger GG Gs Gi Gq GLUCAGON AND."— Presentation transcript:

1 Glucagon Adrenaline glucagon adrenergic 2121 cAMP IP 3 DAG Ca 2+ PKC PKA inactive HormoneReceptorsubtype 2 nd messenger GG Gs Gi Gq GLUCAGON AND ADRENALINE ACTION - REGULATION OF METABOLISM Regulation of enzyme activity Metabolic responseFUEL MOBILISATION

2 FA + glycerol triglyceride ADIPOSE TISSUE BRAIN CO 2 + H 2 O MUSCLE glycogen CO 2 + H 2 O FA AA protein FA – fatty acids AA – amino acids LIVER glucoseglycogen AA glucose glycerol Glucagon acts on liver to maintain blood glucose levels (gluconeogenesis and glycogenolysis) Adrenaline acts on: muscle – glycogenolysis liver - glycogenolysis adipose – lipolysis tissue glucose Overview of fuel mobilisation in different tissues glycogenolysis gluconeogenesis lipolysis

3 glycogen glucose-1-P Regulation of glycogenolysis by glucagon and adrenaline (remember also allosteric regulation – see Prof. Denton's lectures) PHOSPHORYLASE GLYCOGEN SYNTHASE PKA glucagon adrenaline (β) - P + PKA glucagon adrenaline (β) P

4 phosphorylase kinase b phosphorylase kinase a P PKA phosphorylase bphosphorylase a P PKA acts on phosphorylase kinase glycogen n n-1 + glucose 1-P glucose-6-P glucose (liver) glycolysis & TCA cycle (muscle)

5 glycogen synthase a P glycogen synthase b PKA (inactive) PKA directly phosphorylates glycogen synthase + UDP glucose glucose 1-P glycogen n n-1 -

6 phosphorylase kinase b phosphorylase kinase a P PKA PP-1 Inhibitor proteinP - Protein phosphatase-1 is inactivated by an inhibitor protein Pi ATP ADP glycogen synthase a P glycogen synthase b PP-1 PKA (inactive) Inhibitor protein PKA Inhibitor proteinP - AMPLIFICATION occurs by simultaneous activation of glycogen breakdown and inhibition of glycogen synthesis

7 Activation of phosphorylase kinase by Ca 2+ and PKA    adrenergic receptors Ca 2+  subunit is calmodulin Ca 2+  subunit is catalytic     phosphorylase kinase P P PKA  4Ca 2+ P P P % activity [Ca 2+ ] M 30-fold increase in phosphorylase kinase activity

8 Glucagon stimulates gluconeogenesis in liver - role of F2,6,P 2 pyruvate oxaloacetate phosphoenol pyruvate PC PEPCK PK F2,6P 2 + F2,6P 2 F6P FBPase2 PFK-2 amino acids, lactate PKA + Glucagon Net result is to decrease F2,6,P 2 FBPase1 PFK-1 F1,6P F6P glucose 6-P glucose glucose-6 phosphatase PKA PC and PEPCK subject to long-term regulation glycerol

9 Adrenaline stimulates glycolysis in muscle (heart) pyruvate phosphoenol pyruvate F1,6P F6P glucose 6-P PFK-1 FBPase1 F2,6P 2 + TCA cycle Gycogen PKA + F2,6P 2 F6P FBPase2 PFK-2 Heart has a different isoform of FBPase2/PFK2

10 Regulation of triglyceride breakdown (lipolysis) Triglyceride fatty acids + glycerol triglyceride lipase P triglyceride lipase PKA

11 Net effect of adrenaline……….. (Fight-or-flight response) “mobilisation of energy resources and shunting to where they are most needed to prepare the body for sudden action” increase heart rate and force Smooth muscle relaxation (bronchi and skeletal muscle) Smooth muscle contraction in peripheral organs (e.g. skin/kidney) Smooth muscle relaxation (gut) glycogen breakdown triglyceride breakdown stimulate glucagon release inhibit insulin release


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