Biochemistry · Topic
Uronic acid pathway !
This side route of glucose makes UDP-glucuronic acid for detoxification and for building connective tissue. It explains why humans cannot make vitamin C.
Updated 2026-11-01
Key facts
- Glucose 6-phosphate → glucose 1-phosphate → UDP-glucose → UDP-glucuronic acid (UDP-glucose dehydrogenase, 2 NAD⁺).
- UDP-glucuronic acid is used for conjugation (bilirubin, drugs, steroids: glucuronidation) and for glycosaminoglycans (hyaluronan, chondroitin, heparin, dermatan).
- Free glucuronate → L-gulonate (NADPH). In most animals L-gulonolactone oxidase then makes ascorbic acid; humans, other primates and guinea pigs lack it, so vitamin C is essential.
- L-gulonate → L-xylulose → xylitol → D-xylulose → D-xylulose 5-phosphate, which enters the pentose phosphate pathway.
- No ATP is produced; L-xylulose reductase deficiency causes essential pentosuria (harmless L-xylulose in urine).
In detail
- 1. UDP-glucose dehydrogenase oxidises carbon 6 of glucose to a carboxyl group, using two NAD⁺.
- 2. UDP-glucuronosyltransferases (UGT) transfer the glucuronate to bilirubin and many drugs, making them water-soluble.
- 3. In the ER, UDP-glucuronate also gives UDP-xylose, the first sugar of proteoglycan linker chains.
- 4. Free glucuronate is reduced to L-gulonate; humans have a non-functional gene for L-gulonolactone oxidase (GULO).
- 5. L-gulonate is oxidised and decarboxylated to L-xylulose; L-xylulose reductase (gene DCXR) reduces it to xylitol, which is oxidised to D-xylulose.
- 6. Some drugs (barbiturates, chlorobutanol) increase flow through the pathway and urinary glucuronate and L-xylulose.
- Also called
- Glucuronic acid pathway, Essential pentosuria, Why humans need vitamin C
Clinical notes
- Essential pentosuria is benign but gives a positive test for reducing sugars in urine, which can be mistaken for diabetes.
- Lack of dietary vitamin C causes scurvy because humans cannot complete this pathway to ascorbate.
- Neonates have low UGT activity, one cause of physiological jaundice; inherited UGT1A1 defects cause Gilbert and Crigler–Najjar syndromes.
Pathways
Related conditions
Related
- Glucuronidation
- UDP-glucose
- Glucose 6-phosphate
- Pentose phosphate pathway
- Vitamin C (ascorbic acid)
- Glycosaminoglycans (mucopolysaccharides)
- Bilirubin
- UGT1A1 (bilirubin UDP-glucuronosyltransferase)
- NADPH
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme forms UDP-glucuronic acid and which coenzyme does it use?
UDP-glucose dehydrogenase, using two NAD⁺.
Why must humans obtain vitamin C from the diet?
They lack a working L-gulonolactone oxidase, the last enzyme of ascorbate synthesis in the uronic acid pathway.
What enzyme is missing in essential pentosuria, and what appears in urine?
L-xylulose reductase (DCXR); L-xylulose appears in urine, harmlessly.
What are two uses of UDP-glucuronic acid?
Conjugation of bilirubin, drugs and steroids (glucuronidation) and synthesis of glycosaminoglycans such as hyaluronan.
Through which intermediate does the pathway rejoin the pentose phosphate pathway?
D-xylulose 5-phosphate.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Essential pentosuria: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Vitamins: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.