section 15 3
Alternative Pathways of Glucose Metabolism and Hexose Interconversions
295
Glucose 6-P — -
CH.OH
CH.OH
o—
P UTP
UDPG-
pyrophosphorylase
HO
Glucose-1-P
COOH
HO
.OH
o-Glucuronic acid
(hemiacetal form)
PP,
HO'
OH
HO
UDP-giucose
COOH
Phosphatase
v
v
I \ 0 H
/C H
F»
H P
HO\V
/0—P—P—U
HO
D-Glucuronic
acid 1-phosphate
2NAD
HP
2NADH + 2H+
UDPG-
dehydrogenase
COOH
,
V
------- V
i\0 H
/ 0 — P
UMP
H P
H O Y
/ 0 — P — P — U
HO
UDP-glucuronic acid
Glucuronides
(Spontaneous)
N.
C'
i
H
C
OH
Glucuronate
I
reductase
HO— C — H
f
V
I
NADPH
NADP+
H — C — OH
+ h+
H — C — OH
COOH
D-Glucuronic acid
(open-chain form)
CH 2OH
COO H
H— c — OH
1
1
HO— c — H
1
HO— c — H
1
0
HO— C — H
H — c — OH
1
H — C — OH
I
H — C — OH
1
HO— C — H
1
COOH
1
CH*OH
Spontaneous
HO— C — H
I
HO—C—H
H — c --------
uGulonic acid
HO— C — H
I
C H P H
i-Gulonolactone
f^N A D H + H+
(This conversion is absent
in humans, other primates,
and guinea pigs)
2-Keto- L-gulonoIactone
I
l -Ascorbic acid
Xylulose 5-P
Pentose phosphate
pathway
Oxalate
FIGURE 15-15
Glucuronic acid pathway. The first part consists of synthesis of UDP-glucuronic acid and release of free
D-glucuronic acid. The second part is the metabolism of D-glucuronic acid. D-Glucuronic acid is written as both
the cyclic hemiacetal and the open-chain aldohexose and two orientations of L-gulonic acid and D-xylulose are
shown. P = phosphate.
bond in the product. UDP is hydrolyzed to UMP (uridine
monophosphate) and inorganic phosphate, further ensur-
ing the irreversibility of the coupling reaction.
Because glucuronic acid is highly polar, its conju-
gation with less polar compounds, such as steroids,
bilirubin, and some drugs, can reduce their activity and
make them more water-soluble, thus facilitating renal ex-
cretion. Glucuronic acid is a component of the structural
polysaccharides called glycosaminoglycans (hyaluronic
acid and other connective tissue polysaccharides; see
