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MetaCyc Enzyme: xanthine dehydrogenase

Species: Clostridium cylindrosporum

Subunit composition of xanthine dehydrogenase = [xanthine dehydrogenase subunit]

Summary:
xanthine dehydrogenase is a seleno-molybdo-iron-sulfur flavoprotein that belongs to the family of molybdenum hydroxylases. These enzymes contain FAD, a molybdenum cofactor, and at least one Fe/S center. In addition, these proteins have an additional sulfur or selenium atom, which is required for activity [Meyer00, Self00].

The enzyme has been purified about 26-fold from extracts of Clostridium cylindrosporum grown on urate. Basal activity in cell extracts was about 0.95 μmol/min/mg protein. Addition of selenite and molybdate increased the activity almost 4 fold to 3.7 μmol/min/mg protein [Wagner79].

The clostridial enzyme has a relatively broad substrate specificity, attacking purines preferentially in the 8-position, although the 2- and 6- position are also attacked with some purines. While the primary function of the enzyme is the oxidation of urate, many purines were oxidized with a relatively high specific activity, and were presumed to also be in vivo substrates for the enzyme [Bradshaw60]. However, the much more recent characterization of another enzyme from these organisms ( purine hydroxylase) that is specific to purines, suggests that xanthine dehydrogenase may only accept urate as the in vivo substrate [Self00].

Since the enzyme adds only one oxygen at a time, certain substrates require several steps before they are converted to xanthine. For example, purine is first oxidized to 8-hydroxypurine, which is oxidized to 6,8-dihydroxypurine, urate, and finally xanthine [Bradshaw60].

Gene-Reaction Schematic

Gene-Reaction Schematic

Credits:
Created 28-Mar-2007 by Caspi R, SRI International


Enzymatic reaction of: 6,8-dihydroxypurine hydroxylase (xanthine dehydrogenase)

Inferred from experiment

6,8-dihydroxypurine + 2 NAD+ + H2O → urate + 2 NADH + 2 H+

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: purine nucleobases degradation I (anaerobic), purine nucleobases degradation II (anaerobic)


Enzymatic reaction of: hypoxanthine hydroxylase (xanthine dehydrogenase)

Inferred from experiment

hypoxanthine + H2O → 6,8-dihydroxypurine

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: purine nucleobases degradation II (anaerobic)


Enzymatic reaction of: 8-hydroxypurine hydroxylase (xanthine dehydrogenase)

Inferred from experiment

8-hydroxypurine + H2O → 6,8-dihydroxypurine

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: purine nucleobases degradation II (anaerobic)


Enzymatic reaction of: purine hydroxylase (xanthine dehydrogenase)

Inferred from experiment

purine + an oxidized unknown electron acceptor + H2O → 8-hydroxypurine + an reduced unknown electron acceptor

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: purine nucleobases degradation II (anaerobic)


Enzymatic reaction of: xanthine:NAD+ oxidoreductase (xanthine dehydrogenase)

Inferred from experiment

EC Number: 1.17.1.4

xanthine + NAD+ + H2O ⇄ urate + NADH + H+

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction of enzyme catalysis.

This reaction is reversible.

Alternative Substrates for urate: 6,8-dihydroxypurine [Bradshaw60], 8-hydroxypurine [Bradshaw60], purine [Bradshaw60]

In Pathways: purine nucleobases degradation I (anaerobic), purine nucleobases degradation II (anaerobic)

Cofactors or Prosthetic Groups: Se0 [Wagner79], FAD [Bradshaw60], MoO2-molybdopterin cofactor [Bradshaw60], Fe3+ [Bradshaw60]

Kinetic Parameters:
Substrate Km (μM) Citations
xanthine 40.0 [Bradshaw60]

References

Bradshaw60: Bradshaw, W.H., Barker, H.A. (1960). "Purification and properties of xanthine dehydrogenase from Clostridium cylindrosporum." J. Biol. Chem. 235(12): 3620-3629.

Meyer00: Meyer O, Gremer L, Ferner R, Ferner M, Dobbek H, Gnida M, Meyer-Klaucke W, Huber R (2000). "The role of Se, Mo and Fe in the structure and function of carbon monoxide dehydrogenase." Biol Chem 381(9-10);865-76. PMID: 11076018

Self00: Self WT, Stadtman TC (2000). "Selenium-dependent metabolism of purines: A selenium-dependent purine hydroxylase and xanthine dehydrogenase were purified from Clostridium purinolyticum and characterized." Proc Natl Acad Sci U S A 97(13);7208-13. PMID: 10860985

Wagner79: Wagner R, Andreesen JR (1979). "Selenium requirement for active xanthine dehydrogenase from Clostridium acidiurici and Clostridium cylindrosporum." Arch Microbiol 121(3);255-60. PMID: 518233


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.5 on Wed Feb 10, 2016, BIOCYC11A.