Uronic Acid Pathway

• Uronic acids are a class of sugar acids with both carbonyl and carboxylic acid functional groups.
• They are sugars in which the terminal carbon’s hydroxyl group has been oxidized to a carboxylic acid.
• Oxidation of the terminal aldehyde instead yields an aldonic acid, while oxidation of both the terminal hydroxyl group and the aldehyde yields an aldaric acid.
• The names of uronic acids are generally based on their parent sugars, for example, the uronic acid analog of glucose is glucuronic acid.
• Uronic acids derived from hexoses are known as hexuronic acids and uronic acids derived from pentoses are known as penturonic acids.

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. 

• Uronic acid pathway is an alternative oxidative pathway for glucose metabolism.
• It catalyzes the conversion of glucose to glucuronic acid, ascorbic acid, and pentoses.
• It does not lead to the formation of ATP.

Location

• In cytoplasm of the cell
• Tissue distribution: Liver and Adipose tissue

Steps of Uronic Acid Pathway

• STEP 1: Glucose 6-phosphate is converted to Glucose1-phosphate via phosphoglucomutase.
• STEP 2: Glucose 1-phosphate reacts with uridinetriphosphate (UTP) via UDP glucosepyrophosphorylase to form UDP glucose.
• STEP 3: UDP glucose is oxidized at C6 by a 2-step process via an NAD +-dependent UDP glucosedehydrogenase  to form UDP glucuronic acid.
• STEP 4: UDP glucuronic acid is hydrolysed to form UDP and D-glucuronic acid.

UDP-glucuronate

• Source of glucuronate for reactions involving its incorporation into proteoglycans.
• conjugated to nonpolar acceptor molecules such as steroid hormones, some drugs, bilirubin, or other foreign compounds in the liver for easier excretion via the bile.
• STEP 5: Oxidation of D-glucuronic acid to L-gulonic acid via L- gulonic dehydrogenase   in the presence of NADPH₂.

L-gulonate

• It is the direct precursor of ascorbate in those animals capable of synthesizing this vitamin, in an NADPH-dependent reaction.
• In humans, ascorbic acid cannot be synthesized because of the absence of L-gulonolactone oxidase.
• STEP 6: Oxidation of L-Udonic acid
  • L-gulonic acid may be oxidized to 3-keto-L-gulonicacid via β -L-hydroxy acid dehydrogenase.
  • NADH is generated.
• STEP 7: Decarboxylation of 3-Keto-L-Gulonic Acid
  • Followed by decarboxylation of 3-keto-L-gulonicacid to form L-xylulose,a ketopentose via β-L- gulonate decarboxylase ; here, carbon 1 of 3-keto-L-gulonic acid is released as CO_2. 
• STEP 8: Oxidation of L-Xylulose
  • L-xylulose is then reduced to xylitol via xylitoldehydrogenase  (or xylulosereductase)
• STEP 9: Reoxidation of Xylitol
• STEP 10: Phosphorylation of D-Xylulose
  • D-xylulose is phosphorylated at carbon 5 to form D-xylulose 5-phosphat via xylulose kinase 
  • Further metabolized via the HMP Shunt
  • Converted to intermediates of glycolysis for energy production

Regulation of Uronic Pathway

• Administration of drugs i.e. Chlorobutanol & Barbital significantly increases the uronic acid pathway.
• Certain drugs are also found to enhance the synthesis of Ascorbic acid.

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Significance of Uronic Pathway

• 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.

References

1. 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.
2. John W. Pelley, Edward F. Goljan (2011). Biochemistry. Third edition. Philadelphia: USA.
3. https://www.scribd.com/document/328465491/2-4-Biochemistry-Tca-Hmp-and-Uronic-Acid-Pathway
4. https://www.slideshare.net/sathi3366/presentation-29571791.