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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.
- 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.
- 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.
- 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 CO2.
- 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.
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.
- 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.