Last time we talked about glucagon and epinephrine

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2 Last time we talked about glucagon and epinephrine *Glucagon it's very important hormone, its nature is a protein look like a polypeptide chain. *Epinephrine hormone it's nature is an amino acid derivative. When Glucose Levels are Low Epinephrine or Glucagon Increases Glucose Concentration by.1 Favoring Glycogen Breakdown (Activates Glycogen Phosphorylase) and.2inhibiting Glycogen Synthesis (Inhibits Glycogen Synthase) Qe:) How glucagon and epinephrine will increase glucose concentration in our blood?? When glucose level is low epinephrine + glucagon will increase glucose concentration in our blood by two mechanisms: 1) Degrade of glycogen immediate product is G1P converted to G6P converted to glucose by G6Pase. 2) Gluconeogenesis pyruvate converted to glucose. Qe:) How glucagon will favor glycogen degradation?! By activation of CAMP by Adenylyl cyclase {glucagon / epinephrine binds its receptors G proteins will activated adenylyl cyclase will activated converts ATP to CAMP}. Page 1

3 Qe:) How CAMP will activate protein kinase A?! CAMP will bind to the regulatory subunits and after it binding catalytic subunits will dissociated from the regulatory subunits and 'll activated then start phosphorylating other proteins like : 1- Glycogen phosphorylase B: It'll activated by phosphorylation converted to glycogen phosphorylase A degrade glycogen to G1P. "If we have 100 branches of glycogen we'll have 100 0f free " )عدد غير محدود ) G1P glucose, and ( n) number of 2- Glycogen synthase: It'll inhibited by phosphorylation converted to glycogen synthase B no more glucose turning to glycogen (glucose will be available).and also it will increases glycogenesis by inhibit pyruvate kinase Qe: how PKA will be inhibiting? By phosphorylation PKA glycogenesis will be stimulation. >>> Qe: how insulin will decrease glucose concentration in our blood?? Insulin will increase the uptake of glucose by the cell so it will be decrease the concentration of glucose around. Page 2

4 Qe: what will happen to the glucose that inters the cell by the effect of insulin? It is will be accumulation? Glucose is very poisoning in the cell so it shouldn t be accumulation, it must be oxidation, so insulin will stimulate glycolysis and the same time it will stimulate the glycogenesis. Countering the Epinephrine/Glucagon System is the Insulin System Insulin Stimulates Phosphoprotein Phosphatase to Remove Phosphates From Glycogen Enzymes.1Favoring Glycogen Synthesis (Activates Glycogen Synthase) and.2inhibiting Glycogen Breakdown (Inhibits Glycogen Phosphorylase) Insulin Also Stimulates Uptake of Glucose by Cells, Reducing Blood Glucose Levels Qe: what is Phosphoprotein Phosphatase function? Dephosphorylating of PFK1 and PFK2, to do this action 1) Favoring Glycogen Synthesis (Activates Glycogen Synthase) and.how? By dephosphorylation. 2) Inhibiting Glycogen Breakdown (Inhibits Glycogen Phosphorylase) *remember Insulin Also Stimulates Uptake of Glucose by Cells, except the liver >>cause the glucose will inter without insulin stimulant. Page 3

5 When Glucose Needed Epinephrine/Glucagon Stimulates Phosphorylation and Release of Glucose from Glycogen When Glucose Abundant Insulin Stimulates Dephosphorylation and Incorporation of Glucose into Glycogen *this slide it is very important to understand Odd observation: Start with GPa (active) and GSa (inactive) Add only glucose, get GPb (inactive) and GSb (active) Why? The answer blew Qe: what will be the effect of glucose in GPa? Inhibit by allosteric effect *always in the absent of glucose GPa form. And when glucose is abundant will inhibit convert from (R)state to the (T)state. Page 4

6 THIS IS THE ANSEWE As we see this is the Phosphoprotein Phosphatase and it is association with GPa,up on the addition of glucose Will convert allosteric from R T (INACTIVE),and glycogen phosphatase will change its structure and the result it will dissociation from Phosphoprotein Phosphatase so it is become active.and start glycolysis and glycogenesis. The idea here is: Phosphoprotein Phosphatase (ppase) +addition of glucose dissociation of (ppase) and activation of (ppase) ppase will Page 5

7 Dephosphorylation a lot of protein include glycogen phosphatase and glycogen synthesis. ) اللهم ال سهل إال ما جعلته سهال فأنت جتعل احلزن إن شئت سهال ( موفقين باالمتحان..دعواتكم <3 Page 6