URONIC ACID PATHWAY

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. 

1. CARBOHYDRATE METABOLISM GLUCURONIC ACID PATHWAY Course Incharge : Rabia Khan Baber

2. AIMS AND OBJECTIVES OF PRSENTATION

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.  GLUCURONIC ACID PATHWAY

4. 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.

5. LOCATION

6. STEPS IN URONIC ACID PATHWAY

7. 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 .

8. 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. FATE OF L-GULONIC ACID

9.   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.

10. 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 . SIGNIFICANCE OF URONIC PATHWAY

11. 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. ESSENTIAL PENTOSURIA

12. 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. SUMMARY

13. 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 REFERENCES