The glucuronic acid pathway is a quantitatively minor route of glucose metabolism. Like the pentose phosphate pathway, it provides biosynthetic precursors and inter-converts some less common sugars to ones that can be metabolized.
3. The glucuronic acid pathway is a quantitatively minor
route of glucose metabolism. Like the pentose
phosphate pathway, it provides biosynthetic precursors
and inter-converts some less common sugars to ones
that can be metabolized.
4.
5. This is an alternative oxidative pathway for glucose and
is also known as the glucuronic pathway.
Concerned with the synthesis of glucuronic acid,
pentoses, and vitamin, ascorbic acid (except in primates
and guinea pigs).
Dietary xylulose enters the uronic acid pathway
through which it can participate in other metabolisms.
Glucuronate is a highly polar molecule which is
incorporated into proteoglycans as well as combining
with bilirubin and steroid hormones; it can also be
combined with certain drugs to increase their solubility.
8. 1. Formation of
UDP glucronate
2. Conversion of
UDP-glucuronate
to L gulonate
9.
10. STEP 1
Glucose is converted
into glucose-6
phospahte
Glucose 6-phosphate
is converted to
Glucose1-phosphate
via phosphoglucomuta
se.
STEP 2
Glucose 1-phosphate
reacts with
uridinetriphosphate
(UTP) via
UDP glucosepyrophos
phorylase to form
UDP glucose.
11. STEP 3
UDP glucose is
oxidized at C6 by a
2-step process via an
NAD +-dependent
UDP
glucosedehydrogena
se to form UDP
glucuronic acid.
STEP 4
UDP glucuronic
acid is hydrolysed to
form UDP and D-
glucuronic acid.
12. STEP 5
Oxidation of D-
glucuronic acid to L-
gulonic acid via L-
gulonic
dehydrogenase in the
presence of NADPH.
STEP 6
-L-
gulonic acid may be ox
idized to 3-keto-L-
gulonicacid via β -L-
hydroxy acid
dehydrogenase.
• NADH is generated.
13. STEP 7
Decarboxylation of 3-
keto-L-gulonicacid to
form L-
xylulose,a ketopentose
via β-L- gulonate
decarboxylase
STEP 8
Oxidation of L-
Xylulose
• Lxylulose is then red
uced to xylitol via
xylitoldehydrogenase
(or
xylulosereductase)
14. STEP 9 Reoxidation of Xylitol
STEP 10
Phosphorylation of D-
Xylulose
• Dxylulose is phosphorylat
ed at carbon 5 to form D-
xylulose 5-phosphat via
xylulose kinase
• Further metabolized via
the HMP Shunt
• Converted to
intermediates of glycolysis
for energy production
15. UDP-glucuronate
Source of glucuronate for reactions involving its
incorporation into proteoglycans.
Conjugated to non polar acceptor molecules such as steroid
hormones, some drugs, bilirubin, or other foreign
compounds in the liver for easier excretion via the bile.
L-gulonate
It is the direct precursor of ascorbate in those animals
capable of synthesizing vitamin C , in an NADPH-
dependent reaction.
In humans, ascorbic acid cannot be synthesized because of
the absence of L-gulonolactone oxidase.
16. Fate of L-Gulonic acid is different according to the
animals.
Synthesis of ascorbic acid:
L-Gulonic acid is the direct precursor of Ascorbic acid,
in those animals which are capable of synthesizing this
vitamin.
In those animals, synthesis of vitamin C (Ascorbic
acid) takes place.
17. Fate of L-Gulonic Acid in Humans:
• In man and other primates as well as guinea pigs
ascorbic acid cannot be synthesized.
• The enzyme L-gulonolactone oxidase which converts
gulonate to ascorbic acid is absent in them.
• Therefore, vitamin C has to be supplemented in the diet
for these animals.
• L-Gulonic acid is oxidized to 3-ketoglulonate, which is
then decarboxylated to the pentose L-Xylulose.
• L-xylulose is converted to a D-xylulose via xylitol by a
reduction followed by oxidation.
• The D-xylulose can enter hexose monophosphate
shunt.
18. It is an alternative oxidative pathway for glucose.
It is concerned with the synthesis of glucuronic acid,
pentoses & vitamin-ascorbic acid (except in primates &
guinea pigs).
Major function is to produce D-Glucuronic acid which
is required for: Detoxification of foreign chemicals and
synthesis of mucopolysaccharides.
Many wastes in the human body are excreted in the
urine as their glucuronate salts,
Iduronic acid is a component of some structural
complexes such as proteoglycans.
19. Rare genetic disorder related to the deficiency of NADP
dependent. enzyme xylitol dehydrogenase and xylulose
reductase. The incidence is 1 in 2,500 births.
Due to any of these enzyme defect xylulose cannot be converted
to xylitol.
The affected secrete large amounts of L-xylulose in urine and
gives a
positive Benedict’s test.
Essential pentosuria is asymptomatic and the individuals suffer
from no ill-effects, but it should be differentiated from diabetes
mellitus.
lt has been reported that the administration of drugs aminopyrine
and
antipyrine increases the excretion of L-xylulose in pentosuric
patients.
20. The uronic acid pathway is an alternative pathway for the
oxidation of glucose that does not provide a means of producing
ATP, but is utilized for the generation of the activated form of
glucuronate, UDP-glucuronate.
The uronic acid pathway of glucose conversion to glucuronate
begins by conversion of glucose-6-phosphate is to glucose-1-
phosphate by phosphoglucomutase, and then activated to UDP-
glucose by UDP-glucose pyrophosphorylase.
UDP-glucose is oxidized to UDP-glucuronate by the NAD+-
requiring enzyme, UDP-glucose dehydrogenase.
UDP-glucuronate then serves as a precursor for the synthesis of
iduronic acid and UDP-xylose and is incorporated into
proteoglycans and glycoproteins or forms conjugates with
bilirubin, steroids, xenobiotics, drugs and many compounds
containing hydroxyl (–OH) groups.
21. Rodwell, V. W., Botham, K. M., Kennelly, P. J., Weil, P.
A., & Bender, D. A. (2015). Harper’s illustrated
biochemistry (30th ed.). New York, N.Y.: McGraw-Hill
Education LLC.
John W. Pelley, Edward F. Goljan (2011).
Biochemistry. Third edition. Philadelphia: USA.
Textbook of Biochemistry-U Satyanarayana
Textbook of Biochemistry-DM Vasudevan