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chapter 13
Carbohydrate Metabolism I: Glycolysis and TCA Cycle
TABLE 13-2
Properties of Enzymes o f Glycolysis
Enzyme
Coenzymes and
Cofactors
Allosteric Modulators
Positive
Negative
Equilibrium
Constant
atpH7.0(K'eq)
AG0/
kcal/mol
(
kj/mole)
Hexokinase
Mg2+
ATP, P,
Glucose
6
-
phosphate
650
-4.0 (-16.7)
(nonequilibrium) *
Glucokinase
Mg2+
—
—
—
(nonequilibrium)
Glucose-phosphate
isomerase
Mg2+
—
—
0.5
+0.4 (+1.7)
(near-equilibrium)’
'’
6
-Phosphofructokinase
Mg2+
Fructose 2,6-
bisphosphate,
ADP, AMP, Pj,
K+, nh4+
ATP, citrate
2 2 0
-3.4 (-14.2)
(nonequilibrium)*
Fructose-bisphosphate
aldolase
—
—
0 . 0 0 1
+5.7 (+23.8)
(near-equilibrium)*
Triose-phosphate isomerase
Mg2+
—
—
0.075
+1.8 (+7.5)
(near-equilibrium)*
Glyceraldehyde-3-
phosphate dehydrogenase
NAD
—
—
0.08
+1.5 (+6.3)
(near-equilibrium)*
Phosphoglycerate kinase
Mg2+
—
—
1,500
-4.5 (-18.8)
(near-equilibrium)*
Phosphoglyceromutase
Mg2+, 2,3-bis-
phosphoglycerate
—
—
0 . 0 2
+1.1 (+4.6)
(near-equilibrium)*
Enolase
Mg2+
—
—
0.5
+0.4 (+1.7)
(near-equilibrium)*
Pyruvate kinase^
Mg2+, K+
Fructose 1,6
bisphosphate
ATP, alanine,
acetyl-CoA
2 0 0 , 0 0 0
-7.5 (-31.4)
(nonequilibrium)*
Lactate dehydrogenase
NAD
16,000
-6.0 (-25.1)
(near-equilibrium)*
♦Physiologically irreversible reactions.
’''Physiologically reversible reactions.
tThis reaction, despite a high positive AG° value, is reversible under
i n v i v o
conditions.
^Pyruvate kinase is also regulated by cAMP-dependent phosphorylation. The dephosphorylated form is more active, and the phosphorylated form is
less active.
Hexokinase IV, known as
glucokinase,
differs function-
ally from hexokinases I—
III. Glucokinase, a monomeric
protein (M.W. 50,000), has a higher
Km
for glucose
(5 mM) compared to hexokinases I—
III, is found only
in hepatocytes (liver parenchymal cells) and pancre-
atic (islet)
ß
cells, and is not inhibited by glucose-
6
-
phosphate. The function of glucokinase in hepatocytes
and
ß
cells are different and this difference is consistent
with their metabolic function. During postprandial and
hyperglycemic periods, hepatocyte glucose uptake is in-
creased due to increased levels of glucokinase. Thus, the
hepatocyte glucokinase initiates the metabolism of glu-
cose and maintains a gradient of inward flow with glucose
being converted to other metabolic products. During pe-
riods of hypoglycemia (e.g., starvation), the hepatocyte
glucokinase levels are reduced and the liver becomes a
provider of glucose.
In
fi
cells, glucokinase functions as a glucose sensor
and modulates insulin secretion. As the plasma levels of
glucose increase with the resultant increase in cytosolic
glucose concentration in /3 cells, glucokinase determines
the rate of glucose phosphorylation, glycolytic flux, and,
hence, the ATP/ADP ratio. As ATP levels increase, it binds
to the ATP-binding K+ cassette transporter located in the
plasma membrane (Chapter 12) and blocks the K+ efflux
from the cell. This ATP-dependent K+ channel is known
as the
sulfonylurea receptor
because sulfonylurea drugs
used in the treatment of diabetes mellitus type
2
bind and
block the channel. Inhibition of K+ efflux and the result-
ing cell depolarization opens the voltage-sensitive Ca2+
