UDP-glucose to UDP-glucuronate, then glucuronate to xylulose 5-phosphate, which joins the pentose phosphate pathway
Route: UDP-Glc → UDP-glucuronate → Phenyl glucuronide (example glucuronide) → Glucuronate → L-Gulonate → 3-Dehydro-L-gulonate → L-Xylulose → Xylitol → D-Xylulose → Xylulose 5-phosphate
UDP-glucose dehydrogenase oxidizes carbon 6 of the glucose unit of UDP-glucose twice, which uses two NAD⁺ and makes UDP-glucuronate. UDP-glucuronate is the donor for glucuronosyltransferases (UGTs). These enzymes attach glucuronate to drugs and other foreign compounds, which makes them more soluble and easier to excrete. The drawing uses phenyl glucuronide as one example of the many products. Beta-glucuronidase can cut such a conjugate and release free glucuronate. In the glucuronate pathway as KEGG lists it for humans, aldehyde reductase then reduces glucuronate to L-gulonate with NADPH. L-gulonate dehydrogenase (CRYL1) oxidizes it to 3-dehydro-L-gulonate, a decarboxylase removes CO₂ to give L-xylulose, and L-xylulose reductase uses NADPH to make xylitol. Sorbitol dehydrogenase, which KEGG lists for this step in humans, then oxidizes xylitol with NAD⁺ to D-xylulose, and xylulokinase uses ATP to make xylulose 5-phosphate, an intermediate of the pentose phosphate pathway. In animals that make vitamin C, L-gulonate becomes L-gulono-1,4-lactone (KEGG assigns regucalcin, a lactonase, to this step), and L-gulonolactone oxidase makes ascorbate (vitamin C) from the lactone. The gene for this oxidase is a pseudogene in the human genome, so humans cannot make vitamin C and need it in the diet. Two structures are partial. The UGT entry holds only the domain that binds UDP-glucuronate. The decarboxylase entry is the human protein C11orf54, deposited as a hypothetical protein (PTD012); the file itself carries no EC number, and UniProt names it beta-keto L-gulonate decarboxylase with EC 4.1.1.34.
Practice this pathway All pathways
| Step | Enzyme | EC | In | Out |
|---|---|---|---|---|
| 1 | UDP-glucose dehydrogenase | 1.1.1.22 | NAD⁺, H₂O | NADH |
| 2 | UDP-glucuronosyltransferase | 2.4.1.17 | UDP | |
| 3 | β-Glucuronidase | 3.2.1.31 | H₂O | |
| 4 | Aldehyde reductase (glucuronate reductase) | 1.1.1.2 | NADPH | NADP⁺ |
| 5 | L-Gulonate 3-dehydrogenase | 1.1.1.45 | NAD⁺ | NADH |
| 6 | 3-Dehydro-L-gulonate decarboxylase | 4.1.1.34 | CO₂ | |
| 7 | L-Xylulose reductase | 1.1.1.10 | NADPH | NADP⁺ |
| 8 | Sorbitol dehydrogenase (xylitol dehydrogenase) | 1.1.1.14 | NAD⁺ | NADH |
| 9 | Xylulokinase | 2.7.1.17 | ATP | ADP |
Build any of these from its atoms.
Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).