The glucagon signaling pathway in liver cells (shown in the following illustration)…

The glucagon signaling pathway in
liver cells (shown in the following illustration) activates glycogen
degradation through a series of amplification steps, including
(1) stoichiometric binding of glucagon to the glucagon receptor, (2)
Gs_ stimulation of adenylate cyclase (AC), (3) cAMP activation
of protein kinase A (PKA), (4) protein kinase A activation of phosphorylase
kinase (PhK), (5) phosphorylase kinase activation of glycogen
phosphorylase (Ph), and (6) glycogen degradation and release of glucose. Note
that the enzyme cAMP phosphodiesterase
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The glucagon signaling pathway in
liver cells (shown in the following illustration) activates glycogen
degradation through a series of amplification steps, including
(1) stoichiometric binding of glucagon to the glucagon receptor, (2)
Gs_ stimulation of adenylate cyclase (AC), (3) cAMP activation
of protein kinase A (PKA), (4) protein kinase A activation of phosphorylase
kinase (PhK), (5) phosphorylase kinase activation of glycogen
phosphorylase (Ph), and (6) glycogen degradation and release of glucose. Note
that the enzyme cAMP phosphodiesterase (cAMP PDE) cleaves cAMP to terminate
glucagon signaling.

a. Which enzymes in the cascade are
regulated by covalent modification? b. Calculate the theoretical number of
molecules of glucose-1-phosphate generated per second from glycogen as a result
of the interaction of one molecule of glucagon with its receptor on a
liver cell membrane using the following assumptions: (i) Ten Gs_–GTP are
formed for each molecule of glucagon bound to a receptor molecule. (ii) None of
the downstream enzymes are rate limiting for the upstream glucagon signal.
(iii) Adenylate cyclase, protein kinase A, phosphorylase kinase, and glycogen
phosphorylase have a catalytic turnover rate of 1,000 per second. (iv) cAMP
phosphodiesterase is equimolar to adenylate cyclase and has a catalytic
turnover rate of 100 per second. (v) Two cAMP are required to activate
one protein kinase A catalytic subunit (see Figure 8.26)

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