URONIC ACID PATHWAY

URONIC ACID METABOLISM

1. Uronic Acid pathway Gandham . Rajeev Email:[email protected]

2. An alternative oxidative pathway for glucose & is also known as glucuronic acid pathway. Concerned with the synthesis of glucuronic acid, pentoses & vitamin-ascorbic acid (except in primates & guinea pigs).

3. Importance of glucuronic acid pathway It provides UDP- glucuronic acid, which is the active form of glucuronic acid Conjugation of bilirubin Conjugation of steroids Conjugation of various drugs which will make them more water soluble and more easily excreatable. Synthesis of glycosamino glycans (GAG).

4. Formation and importance of UDP – glucuronate Glucose 6-phosphate is first converted to Glucose 1-phosphate by phosphoglucomutase UDP-glucose is synthesized by the enzyme UDP-glucose pyrophosphorylase . UDP glucose dehydrogenase oxidizes UDP-glucose to UDP- glucuronate .

5. Conversion of UDP – glucuronate to L – gulonate UDP glucuronate loses its UDP moiety in a hydrolytic reaction and releases D- glucuronate by the enzyme glucuronidase . D- glucuronate is reduced to L- gulonate by an NADPH-dependent reaction.

6. Synthesis of ascorbic acid in some animals L- gulonate is the precursor for the synthesis of ascorbic acid in many animals. The enzyme L- gulonolactone oxidase , which converts gulonate to ascorbic acid. L- gulonolactone oxidase is absent in man, other primates and guinea pigs. Vitamin C has to be supplemented in the diet for these animals.

7. Oxidation of L- gulonate L- Gulonate is oxidized to 3-ketogulonate & decarboxylated to a pentose, L- xylulose . L- xylulose is converted to D- xylulose via xylitol by a reduction (NADPH-dependent) followed by an oxidation (NAD + dependent) reaction. The D- xylulose after phosphorylaton enter the HMP shunt for further metabolism.

8. Uronic acid pathway

9. Effect of drugs on Uronicacid pathway Administration of drugs (barbital, chloro butanol ) increases the uronic acid pathway to achieve more synthesis of glucuronate from glucose. Certain drugs ( aminopyrine , antipyrine ) were found to enhance the synthesis of ascorbic acid in rats.

10. Essential pentosuria Rare genetic disorder. Due to deficiency of the enzyme NADP-dependent enzyme xylitol dehydrogenase . Due to this, L- xylulose cannot be converted to xylitol . The affected individuals excrete large amounts of L- xylulose in urine & gives a positive Benedicts test.

11. Essential pentosuria is asymptomatic. Barbiturates, aminopyrine , etc will induce uronic acid pathway and will increase the excretion of L- xylulose .

12. References Textbook of Biochemistry-U Satyanarayana Textbook of Biochemistry-DM Vasudevan

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