462 Chapter 15 Enzyme RegulationNot

462 Chapter 15 Enzyme Regulation
Note that three of these types of covalent modification require nucleoside triphos-
phates (ATP, UTP) that are related to cellular energy status; another relies on re-
ducing potential within the cell, which also reflects cellular energy status.
15.5 Is the Activity of Some Enzymes Controlled by Both
Allosteric Regulation and Covalent Modification?
Glycogen phosphorylase, the enzyme that catalyzes the release of glucose units from
glycogen, serves as an excellent example of the many enzymes regulated both by al-
losteric controls and by covalent modification.
The Glycogen Phosphorylase Reaction Converts Glycogen
into Readily Usable Fuel in the Form of Glucose-1-Phosphate
The cleavage of glucose units from the nonreducing ends of glycogen molecules is
catalyzed by glycogen phosphorylase, an allosteric enzyme. The enzymatic reaction
involves phosphorolysis of the bond between C-1 of the departing glucose unit and
the glycosidic oxygen, to yield glucose-1-phosphate and a glycogen molecule that is
shortened by one residue (Figure 15.11). (Because the reaction involves attack by
phosphate instead of H2O, it is referred to as a phosphorolysis rather than a hy-
drolysis.) Phosphorolysis produces a phosphorylated sugar product, glucose-1-P,
which is converted to the glycolytic substrate, glucose-6-P, by phosphoglucomutase
(Figure 15.12). In muscle, glucose-6-P proceeds into glycolysis, providing needed
energy for muscle contraction. In the liver, hydrolysis of glucose-6-P yields glucose,
which is exported to other tissues via the circulatory system.
Glycogen Phosphorylase Is a Homodimer
Muscle glycogen phosphorylase is a dimer of two identical subunits (842 residues,
97.44 kD). Each subunit contains an active site (at the center of the subunit) and an
allosteric effector site near the subunit interface (Figure 15.13). In addition, a regula-
CH2OH
O
O
CH2OH
O
O
CH2OH
O
O
CH2OH
O
O
+
CH2OH
O
CH2OH
O
O
CH2OH
O
O
CH2OH
O
OPO3
2– O
OH
HO
HO
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
HO
Nonreducing end residues
n
n – 1
-D-Glucose-1-phosphate
Pi
FIGURE 15.11 The glycogen phosphorylase reaction. residues
HOCH2
O H H
H
H
HO
OH
OH
OPO3
2–
H
2–O3POCH2
O H H
H
H
HO
OH
OH
OH
H
FIGURE 15.12 The phosphoglucomutase reaction. Glucose-1-phosphate Glucose-6-phosphate