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LET'S TALK LIFE-SCIENCE BIOCHEMISTRY

Suraj Prakash Sharma | Ekta Chotia

GLYCOGENOLYSIS
124

17.1.5.   Fate of Glucose -1- Phosphate

Glucose 1 Phosphate formed by the phosphorylase has two fates according to the requirement of body-In muscles – Glucose -1- Phosphate is converted to Glucose -6- Phosphate by the enzyme phosphoglucomutase. This Glucose -6- Phosphate is redirected towards the glycolysis and provides energy. Hereby it bypasses the activation step of glucose to glucose 6 phosphate hence save one molecule of ATP. In high working muscles net yield of ATP per glucose to lactate is 3 rather than 2.

17.2.      The overall equation is

Glycogen(n glucose residues) + 3 ADP + 3 Pi → glycogen + 2 lactate + 3 ATP(n-1 glucose residues)

In liver – Glucose -6- Phosphate formed from Glucose -1- Phosphate, is dephosphorylated by the enzyme glucose -6- phosphatase and free glucose is released in blood for uptake by other cells by the glucose transporters present in cell membrane.

Glucose-6-phosphate + H2O → Glucose + Pi

17.3.      Regulation of glycogen metabolism

This enzyme is allosterically regulated by AMP, ATP And Glucose-6-phosphate. ATP and glucose-6-phosphate produce a negative effect on the cooperativity of substrate binding. While AMP has positive effect.

The enzyme exist in only two conformations designated R and T. These conformations are in equilibrium R  \leftrightarrow  T.  The substrates bind when the enzyme is in the R state. Positive allosteric effectors bind to the R state and stabilize it shifting the equilibrium to the left. Negative allosteric effectors bind to the T state and stabilize it shifting the equilibrium to the right.

This enzyme binds inorganic phosphate cooperatively. This allows the enzyme’s activity to increase by great amounts over a narrow range of substrate concentrations.

17.3.1.   Regulation of glycogenolysis is by the phosphorylation cascades

The conversion of inactive glycogen phosphorylase ‘b’ to active glycogen phosphorylase ‘a’ is dependent upon the phosphorylation cascade through cyclic AMP-dependant Protein Kinase A (PKA) which is a Ser/Thr kinase which in turn is activated by cyclic AMP.

Both hormones Adrenaline (epinephrine, which is released in response to a threat or stress - the ‘fight-or-flight’ response) and glucagon, (which is released by pancreatic alpha cells in response to low blood glucose levels), stimulate glycogenolysis by binding to their respective receptors (both of which are G-protein coupled receptors) which activates membrane localized protein adenyl cyclase. Adenyl cyclase forms cAMP from ATP then activates PKA. Which stimulates glycogen phosphorylase and inhibits glycogen synthase.

Insulin have counter effect on glycogenolysis. It inhibits glycogenolysis by activating protein phosphatase 1 (PP1) and the enzyme phosphodiesterase which both contribute to the inactivation of glycogen phosphorylase.

Calcium ions

Calcium ions or cyclic AMP (cAMP) act as secondary messengers which is an example of negative control. The calcium ions activate phosphorylase kinase which activates glycogen phosphorylase and inhibits glycogen synthase.

Page no. 124