SECTION 13.1
Glycolysis
227
CHjOH
C H P — ■o— ®
0
\H
G lucokinase
H /q
H exokinase
1/n
\H
G lucose phosphate
®
O'
isom erase
h
V
_
ty o H
A T P ^ ^ A D P h V
____
JO H
H
OH
h
OH
ct-o-Glucose
a-D -G lucose
6
-
phosphate
Ç H - 0 - ®
C = 0
-Ç H ^ O ^ C H P
ûf
____ T
oh
OH
H
D-Fructose
6
-phosphate
A T P '
Mg*
ADP
0
II
^
c—o—®
1
HC— OH
H P — o — ®
1,3-Bisphosphoglycerate
C H P H
Dihydroxyacetone
phosphate
Triosephosphatef
isomerase
j
G lyceraldehyde-3-
9^*®
-
phosphate dehydrogenase
6-Phosphofructokinase
Aldolase
NADH + H
•HC— OH
NAD+, P,
c h —
0 — ®
G lyceraldehyde 3-
phosphate
ADP
Mg
ATP
Phosphoglycerate kinase
CO O ”
I
HÇ— OH
H P — o — ®
3-Phosphoglycerate
Phosphoglyceromutase
® — O — C
F ^ O
^ C
H
— O - ®
hV
____ T °H
OH
H
D-Faictose 1,6-bisphosphate
C O O "
Ç ° °
I
„
Enolase
X ■ n
æn
r
®
2
CH
2
H P — OH
2-Phosphoglycerate
Phosphoenolpym vate
ADP - ^
Pyruvate kinase
Mg-
co o -
1
Lactate
C O O "
1
— C — H
1
dehydroqenase
1
^
"
%
1
CH
3
NAD
NADH
+
H
CHS
L-Lactate
K etopyruvate
O
„
I'
© ----P -
O-
ATP
C O O
(S pontaneous)
(1 _ 0 H
CH
2
Enolpyaivate
FIGURE 13-1
Pathway of glycolysis.
(nonequilibrium) reaction, is accompanied by a substantial
loss of free energy as heat. This phosphorylation initiates
glycolysis and leads to intracellular trapping of interme-
diates (because the plasma membrane is not permeable to
phosphate esters).
Four isoenzymes of hexokinases (types I-IV) con-
stitute a family of enzymes that probably arose from
a common ancestral gene by gene duplication and fu-
sion events. Hexokinases I—
III (M.W. ~ 100,000) have
a
Km
of about 0.1 mM and are allosterically inhibited
by glucose-
6
-phosphate. Due to their low
Km,
hexok-
inases I-III are saturated with the substrate glucose at
concentrations found in plasma. Thus, the overall con-
trol of glucose-
6
-phosphate formation resides in the rate
of glucose transport across the plasma membrane. Hex-
okinase I is expressed in many tissues and is considered
a “housekeeping” enzyme. Hexokinase II is found pri-
marily in insulin-sensitive tissues, namely, heart, skeletal
muscle, and adipose tissue. In these tissues, the glucose
transporter GLUT4 and hexokinase II function in concert
in glucose utilization. Abnormalities in insulin, GLUT4,
or hexokinase II production may be associated with dis-
orders of insulin resistance, obesity, and diabetes mellitus
(Chapter 22).
