MICROBIAL METABOLISM CONTD..
Glycogenolysis :
Glycogen degradation requires the following two reactions:
and degradation are controlled through a complex mechanism involving
insulin, glucagon, and epinephrine, as well as allosteric regulators. Glucagon is
released from the pancreas when blood glucose levels drop in the hours after a meal.
It binds to receptors on hepatocytes and initiates a signal transduction process that
elevates intracellular cAMP levels. cAMP amplifies the original glucagon signal
and initiates a phosphorylation cascade that leads to the activation of glycogen phosphorylase
along with a number of other proteins. Within seconds, glycogenolysis
leads to the release of glucose into the bloodstream.
When occupied, the insulin receptor becomes an active tyrosine kinase
enzyme that causes a phosphorylation cascade that ultimately has the opposite
effect of the glucagon/cAMP system: the enzymes of glycogenolysis are inhibited
and the enzymes of glycogenesis are activated. Insulin also increases the rate
of glucose uptake into several types of target cells, but not liver or brain cells.
Emotional or physical stress releases the hormone epinephrine from the adrenal
medulla. Epinephrine promotes glycogenolysis and inhibits glycogenesis. In
emergency situations, when epinephrine is released in relatively large quantities,
massive production of glucose provides the energy required to manage the
situation. This effect is referred to as the flight-or-fight response. Epinephrine initiates
the process by activating adenylate cyclase in liver and muscle cells.
Calcium ions and inositol trisphosphate are also believed to be involved in epinephrine’s action.
Glycogen synthase (GS) and glycogen phosphorylase have both active and inactive
conformations that are inter converted by covalent modification. The active form
of glycogen synthase, known as the I (independent) form, is converted to the inactive
or D (dependent) form by phosphorylation. The activity of GS can be finely modulated
in response to a range of signal intensities because it is inactivated by
phosphorylation reactions catalyzed by a large number of kinases. Physiologically,
the most important kinases are glycogen synthase kinase 3 (GSK3) and casein kinase
1 (CS1). In contrast to GS, the inactive form of glycogen phosphorylase (phosphorylase
b) is converted to the active form (phosphorylase a) by the phosphorylation of
a specific serine residue. The phosphorylating enzyme is called phosphorylase kinase.
Phosphorylation of both glycogen synthase (inactivating) and phosphorylase kinase (activating) is catalyzed by PKA a protein kinase activated by cAMP. Glycogen synthesis
occurs when glycogen synthase and glycogen phosphorylase have been
dephosphorylated. This conversion is catalyzed by phosphoprotein phosphatase 1
(PP1), which also inactivates phosphorylase kinase. It is noteworthy that PP1 is linked
to both glycogen synthase and glycogen phosphorylase by an anchor protein (p. xx)
called PTG (protein targeting to glycogen).
Several allosteric regulators also regulate glycogen metabolism. In muscle cells,
both calcium ions released during muscle contraction and AMP bind to sites on
glycogen phosphorylase b and promote its conversion to phosphorylase a. The
reverse process, the conversion of glycogen phosphorylase a to phosphorylase b,
is promoted by high levels of ATP and glucose-6-phosphate. Glycogen synthase
activity is stimulated by glucose-6-phosphate. In hepatocytes, glucose is an
allosteric regulator that promotes the inhibition of glycogen phosphorylase .
Glycogen degradation requires the following two reactions:
- Removal of glucose from the non reducing ends of glycogen: Glycogen phosphorylase uses inorganic phosphate (Pi) to cleave the (1,4) linkageson the outer branches of glycogen to yield glucose-1-phosphate. Glycogen phosphorylase stops when it comes within four glucose residues of a branch point.
- Hydrolysis of the a(1,6) glycosidic bonds at branch points of glycogen: Amylo-(1,6)-glucosidase, also called debranching enzyme, begins the
removal of (1,6) branch points by transferring the outer three of the four glucose residues attached to the branch point to a nearby non reducing
end. It then removes the single glucose residue attached at each branch
point. The product of this latter reaction is free glucose. Glucose-1-phosphate, the major product of glycogenolysis, is diverted to glycolysis
in muscle cells to generate energy for muscle contraction. In hepatocytes,
glucose-1-phosphate is converted to glucose, by phosphoglucomutase andglucose-6-phosphatase, which is then released into the blood .
and degradation are controlled through a complex mechanism involving
insulin, glucagon, and epinephrine, as well as allosteric regulators. Glucagon is
released from the pancreas when blood glucose levels drop in the hours after a meal.
It binds to receptors on hepatocytes and initiates a signal transduction process that
elevates intracellular cAMP levels. cAMP amplifies the original glucagon signal
and initiates a phosphorylation cascade that leads to the activation of glycogen phosphorylase
along with a number of other proteins. Within seconds, glycogenolysis
leads to the release of glucose into the bloodstream.
When occupied, the insulin receptor becomes an active tyrosine kinase
enzyme that causes a phosphorylation cascade that ultimately has the opposite
effect of the glucagon/cAMP system: the enzymes of glycogenolysis are inhibited
and the enzymes of glycogenesis are activated. Insulin also increases the rate
of glucose uptake into several types of target cells, but not liver or brain cells.
Emotional or physical stress releases the hormone epinephrine from the adrenal
medulla. Epinephrine promotes glycogenolysis and inhibits glycogenesis. In
emergency situations, when epinephrine is released in relatively large quantities,
massive production of glucose provides the energy required to manage the
situation. This effect is referred to as the flight-or-fight response. Epinephrine initiates
the process by activating adenylate cyclase in liver and muscle cells.
Calcium ions and inositol trisphosphate are also believed to be involved in epinephrine’s action.
Glycogen synthase (GS) and glycogen phosphorylase have both active and inactive
conformations that are inter converted by covalent modification. The active form
of glycogen synthase, known as the I (independent) form, is converted to the inactive
or D (dependent) form by phosphorylation. The activity of GS can be finely modulated
in response to a range of signal intensities because it is inactivated by
phosphorylation reactions catalyzed by a large number of kinases. Physiologically,
the most important kinases are glycogen synthase kinase 3 (GSK3) and casein kinase
1 (CS1). In contrast to GS, the inactive form of glycogen phosphorylase (phosphorylase
b) is converted to the active form (phosphorylase a) by the phosphorylation of
a specific serine residue. The phosphorylating enzyme is called phosphorylase kinase.
Phosphorylation of both glycogen synthase (inactivating) and phosphorylase kinase (activating) is catalyzed by PKA a protein kinase activated by cAMP. Glycogen synthesis
occurs when glycogen synthase and glycogen phosphorylase have been
dephosphorylated. This conversion is catalyzed by phosphoprotein phosphatase 1
(PP1), which also inactivates phosphorylase kinase. It is noteworthy that PP1 is linked
to both glycogen synthase and glycogen phosphorylase by an anchor protein (p. xx)
called PTG (protein targeting to glycogen).
Several allosteric regulators also regulate glycogen metabolism. In muscle cells,
both calcium ions released during muscle contraction and AMP bind to sites on
glycogen phosphorylase b and promote its conversion to phosphorylase a. The
reverse process, the conversion of glycogen phosphorylase a to phosphorylase b,
is promoted by high levels of ATP and glucose-6-phosphate. Glycogen synthase
activity is stimulated by glucose-6-phosphate. In hepatocytes, glucose is an
allosteric regulator that promotes the inhibition of glycogen phosphorylase .
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