Glucuronic Acid: Metabolic Reaction and Importance

In this article we will discuss about the Metabolic Reaction and Importance of Glucuronic Acid.

Metabolic Reactions of Glucuronic Acid:

1. Glucose-6-phosphate is converted to glu­cose-1-phosphate by phosphoglucomutase. The product then reacts with UTP to form UDPG by the help of the enzyme UDPG pyrophosphorylase.

2. UDPG is oxidized to uridine di-phospho-glucuronic acid by UDPG dehydrogenase in presence of NAD⁺. UDP-glucuronic acid is the “active” form of glucuronic acid for reactions involving incorporation of glu­curonic acid into chondroitin sulfate.

3. Glucuronic acid is reduced to L-gulonic acid in the presence of reduced NADP. L-gulonic acid is the precursor of ascor­bic acid.

4. In man and other primates, as well as in guineapigs, L-gulonic acid is oxidized to 3-keto-L-gulonic acid which is then decarboxylated to L-xylulose. L-xylulose is converted to D-xylulose in presence of reduced NADP. D-xylulose, being con­verted to D-xylulose-5-phosphate by ATP, is further metabolized in the HMP shunt.

5. In the rare hereditary disease called “es­sential pentosuria”, large quantities of L- xylulose appear in the urine due to the absence of the enzyme L-xylitol dehydro­genase which can cause reduction of L- xylulosC to xylitol.

Importance of Glucuronic Acid:

1. D-glucuronic acid combines with benzoic acid to form benzoy 1 glucuronide.

2. Phenol combines with D-glucuronic acid to form phenyl-glucuronide.

3. Bilirubin is conjugated with D-glucuronic acid to form mono and di-glucuronides.

4. The drugs and other xenobiotics are first hydroxylated by monooxygenase cyto­chrome P-450 system and then conjugated with D-glucuronic acid.

5. Certain antibiotics like chloramphenicol is also conjugated with D-glucuronic acid.

6. Certain hormones like thyroid hormones and derivatives of certain steroid hormones are detoxicated by D-glucuronic acid.

7. D-glucuronic acid is incorporated to hy­aluronic acid, chondroitin sulphate and heparin.

8. UDP-glucuronic acid, which is the active form, acts as a donor in liver.

9. UDP-glucuronic acid is changed to UDP- L-iduronic acid by the help of UDP-glu­curonic acid-5-epimerase. L-iduronic acid is incorporated in forming dermatan sul­phate (chondroitin sulphate B) in skin.

10. UDP-glucuronic acid is decarboxylated in cornea and cartilage by a specific enzyme and NAD⁺ to form UDP-xylose which is used in the synthesis of mucoprotein.