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.