Dr. Waqas Nawaz PMAS arid agriculture university rawalpindi

1. SUBMITTED TO:
Sir.Raja Tahir
SUBMITTED BY:
Talal Asif (11-arid-974)
Waqas Nawaz (11-arid-975)
DVM 2nd Semester

2. Glucoronic acid (from Ancient Greek"sweet" + "urine") is a carboxylic acid. Its
structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a
carboxylic acid. Its formula is C6H10O7.
The salts and esters of glucuronic acid are known as glucuronates;
the anion C6H9O7− is the glucuronate ion.
Glucuronic acid should not be confused with gluconic acid, a linear carboxylic acid
resulting from the oxidation of a different carbon of glucose. Both glucuronic acid and
gluconic acid are reported to be found in the fermented drink known as kombucha.
IUPAC name
(2S,3S,4S,5R,6R)-3,4,5,6-Tetrahydroxyoxane-2-carboxylic acid
By Norbert Hoffmann:
Glucuronic acid is considered by many to be one of the important key components found in
Kombucha Tea because of its detoxifying action. It is widely distributed in plants, found in
gums, mucilages, saponines etc. and in animals. The related compound, UDPGlucuronic
acid which is the active or co-enzyme form of Glucuronic acid, has been discovered in
several non-Kombucha bacteria by at least eight scientists (Dutton, 1980). Since metabolic
processes in related organisms are generally similar, it can, therefore, be expected that
UDP-Glucuronic acid is also present in the Kombucha bacteria. This, of course, still has to
be substantiated. It is this compound which binds toxins in the body and allows their
elimination. Dutton (1966) states that "the biosynthesis of the simple conjugates of
Glucuronic acid was shown to occur, somewhat ironically, ... by glucuronyl transference from
an 'active' form, UDP (uridinediphosphate)-Glucuronic acid, and (it was) demonstrated that
this nucleotide was derived, in animals, not from glucuronate, but from glucose by way of
UDP-glucose

3. Uronic acid pathway (Glucuronic acid cycle) :
1- The Glc-6-P is converted into Glc-1-P that takes high energy UTP
and becomes UDP-Glc by the enzyme UDP-Glc dehydrogenase
(NAD+ is required).

4. 2- UDP gluclucuronic acid is produced and conjugated with
Glucosamine and Galactosamine to form mucopolysaccharides.
Utilized in detoxification by conjugation with Benzene (phenol),
Bilirubin and other steroids.
3- UDP-glucuronic acid loses UMP and becomes D-glucuronic acid 1-P less, then loses Pi
(phosphate) to become D-glucuronic acid,
which may also come from diet (like meat) and this convert to L-glucuronic acid by
reductase.
4- L-glucuronic acid is either converted into:
a- L-gulonolactone which is converted into 2 keto L-gulonolactone
that results in ascorbic acid (vit. C)
this step is absent in human, primates (Monkeys) and guinea
pigs, because of enzyme absence, So no vit. C is formed. But in
other animals the enzyme’s present and thus vit. C can be
sunthesized.
b- L-Xylulose is formed by decarboxylation and then reduced by
NADPH to L-xylitol (alcohol) which loses H+ to NAD to become
NADH and D-Xylulose results by a reductase enzyme, so if this
enzyme is deficient then L-Xylulose accumulates in the blood,
causing “Essential Pentoseuria”.
D-Xylulose converts to Xylulose 5-P by kinase and by HMP shunt
Ribose-5-P is produced then Frc-6-P and Glyceraldehyde-3-P
are formed and so pyruvic acid that’s oxidized to CO2, H2O and
energy is produced

6. Proteoglycans:
Glucuronic acid is common in carbohydrate chains of proteoglycans. It is part of
mucous animal secretions (such as saliva), cell glycocalyx andintercellular matrix (for
instance hyaluronan)
Glucuronidases:
Glucuronidases are those enzymes that hydrolyze the glycosidic bond between
glucuronic acid and some other compound.
Glucuronidation:
In the animal body, glucuronic acid is often linked to the xenobiotic metabolism of
Substances such as drugs,
pollutants, bilirubin, androgens,estrogens, mineralocorticoids, glucocorticoids, fatty
acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds, and this
linkage process is known as glucuronidation. Glucuronidation occurs mainly in the liver,
although the enzyme responsible for its catalysis, UDP-glucuronyltransferase, has been
found in all major body organs, e.g., intestine, kidneys, brain, adrenal gland, spleen,
and thymus.

7. Glucuronidation in the Cat:
The cat can glucuronidate bilirubin but cannot glucuronidate phenolic compounds
such as phenol and napthol.
Glucuronides:
The substances resulting from glucuronidation are known as glucuronides (or
glucuronosides) and are typically much more water soluble than the non-glucuronic acid-
containing substance from which they were originally synthesised. The human body uses
glucuronidation to make a large variety of substances more water-soluble, and, in this way,
allow for their subsequent elimination from the body through urine or faeces (via bile from the
liver). Hormones may also be glucuronidated to allow for easier transport around the body.
Pharmacologists have linked drugs to glucuronic acid to allow for more effective delivery of a
broad range of substances. Sometimes toxic substances are also less toxic after
glucuronidation,
The conjugation of xenobiotic molecules with hydrophilic molecular species such as
glucuronic acid is known as phase II metabolism
The β-D methyl glycoside of glucuronic acid in the low energy 4C1 conformation
UDP-Glucuronic Acid Functions:
UDP-Glucuronic acid has three major functions:
Detoxification of poisonous substances through conjugation and subsequent elimination.

8. Transport of hormones and other important substances through conjugation and subsequent
release at the target location, tissue etc. .
Intermediate in the biosynthesis of Ascorbic acid (except in primates and guinea pigs).
The Detoxification Process
UDP-Glucuronic acid is formed in the liver of all animals including primates and
conjugates (combines with) poisonous substances making them more water-soluble to allow
for subsequent elimination. This binding of poisonous compounds is catalyzed by the
enzyme UDP-Glucuronyltransferase which has been found in all major body organs, heart,
kidneys, adrenal gland, spleen, thymus etc.
Another enzyme, Glucuronidase, works the opposite way. It can break the conjugated
substances (glucuronides) apart again to free hormones and other chemicals where they
are needed. It is controlled by a substance called Saccharolactone which can inhibit its
action. In addition, naturally occurring bacteria in the intestines use this enzyme to break
down some of the glucuronides into its components, allowing reabsorption of Glucuronic
acid and the conjugated substance (toxin or drug) provided it is lipid soluble, through the
intestinal walls. This explains why certain drugs normally excreted with feces remain in
the body longer than anticipated, for example glutethimide (Doriden) and phenolpthalein.
Toxins with smaller molecules normally are excreted with urine thus escaping
biotransformation by bacterial enzymes.

9. Uses:
Determination of urinary steroids and of steroid conjugates in blood Contained in some
commercially available brands of Kombucha as an antioxidant & organic acid In all plants
and mammals-other than guinea pigs and primates-glucuronic acid is a precursor of ascorbic
acid, also known as vitamin c.