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chapter 15
Carbohydrate Metabolism II: Gluconeogenesis, Glycogen Synthesis and Breakdown, and Alternative Pathways
The reaction is freely reversible, but it is rendered prac-
tically irreversible by hydrolysis of pyrophosphate (PP;)
through the action of pyrophosphatase.
PPi + H20
2Pj
Thus, two high-energy phosphate bonds are hydrolyzed
in the formation of UDP-glucose. Nucleoside diphos-
phate sugars are commonly used as intermediates in
carbohydrate condensation reactions. ADP-glucose is the
precursor for the synthesis of starch in plants and of other
storage polysaccharides in bacteria. In each case, the
high-energy bond between the sugar and the nucleoside
diphosphate provides the energy needed to link the new
sugar to the nonreducing component of another sugar or
polysaccharide.
The next step in the biogenesis of glycogen is ad-
dition of a glucosyl residue at the C-l
position of
UDP-glucose to a tyrosyl group located at position 194 of
the enzyme glycogenin, which is a Mg2+-dependent auto-
catalytic reaction. Glycogenin (M.W. 37,000) extends the
glucan chain, again by autocatalysis, by six to seven glu-
cosyl units in
a{\ —>
4) glycosidic linkages using UDP-
glucose as substrate (Figure 15-7). The glucan primer
of glycogenin is elongated by glycogen synthase using
UDP-glucose. Initially, the primer glycogenin and glyco-
gen synthase are firmly bound in a 1:1 complex. As the
glucan chain grows, glycogen synthase dissociates from
glycogenin.
The branching of the glycogen is accomplished by trans-
ferring a minimum of six a (l —»■
4) glucan units from the
elongated external chain into the same or a neighboring
chain by cc(l —»■
6
) linkage. This reaction of a(l -» 4)
to
a(\
—
6
) transglucosylation creates new non-reducing
ends and is catalyzed by a branching enzyme. A mature
glycogen particle is spherical, containing one molecule of
j^Glycogeninj— Tyrosyl Group
Mg 2+
Autocatalysis
Autocatalysis
UDP-glucose
UDP
■— Glucosyl Unit
UDP-glucose
UDP
Glycogen Synthase
--UDP-glucose
_ i-*-U D P
Branching Enzyme
Glycogen Synthase
*
and Branching Enzyme
| ^-UDP-glucose
— >-UDP
Mature Glycogen (60,000 Glucosyl Units)
(p particle)
FIGURE 15-7
Schematic representation of glycogen biosynthesis. 5, Glucosyl units, (1 —>■
6
) linkage.
