5 The xanthine oxidoreductase enzyme family: xanthine dehydrogenase , xanthine oxidase , and aldehyde oxidase

Author(s):  
Takeshi Nishino ◽  
Ken Okamoto ◽  
Bryan T. Eger ◽  
Emil F. Pai
2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1057.1-1057
Author(s):  
S. Bedina ◽  
A. Trofimenko ◽  
E. Mozgovaya ◽  
M. Mamus ◽  
S. Spitsina

Background:Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the presence of rheumatoid factor (RF) and anticitrulline autoantibodies. Recent evidences suggest that impairment of neutrophil extracellular traps (NETs) could exert substantial influence on RA pathogenesis. The production of NETs depends heavily on the ROS generation. One of its mechanisms is xanthine oxidoreductase (XOR) mediated degradation of purine metabolites. Analysis of pro-oxidant activity of the enzymatic complex XOR and its constituents, xanthine oxidase (XO) and xanthine dehydrogenase (XDG), is an issue of considerable interest in this context.Objectives:Evaluation of XO and XDG activities in RF-positive and RF-negative RA using both plasma and lysed lymphocyte samples.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. Diagnosis of RA had been verified using ACR/EULAR 2010 criteria. Enzymatic activities in plasma and lymphocytes were measured spectrophotometrically and expressed as nmol/min/ml. Enzymatic activities in lymphocytes were also normalized to 1×107 cells/ml. Statististical tests were selected in line with common guidelines. Differences were considered significant when p<0.05. Reference ranges were calculated as means ±2SD.Results:75 adult RA patients (52 females and 23 males, mean age 43.9±0.97 years, mean disease duration 8.5±0.3 years) from the rheumatology unit of Volgograd Clinical Emergency Hospital #25 as well as 35 healthy controls were included in the study. RF-positive RA and RF-negative RA were observed in 49 (65.3%) and 26 (34.7%) patients, respectively. Reference ranges for plasma and lymphocyte XO activities were 2.60-3.96 and 14.2-27.8 nmol/min/ml, respectively. Similar ranges for XDG activities were 4.49-5.93 and 22.5-40.7 nmol/min/ml, respectively. Enzymatic profile of RA patients is characterized by significantly increased XO activity in plasma and decreased XO and XDG activities in lymphocytes (р<0.001). XO activity is increased (p<0.001), XDG activity is decreased (p<0.001) in blood plasma of patients with RF-negative RA, while the activity of both enzymes is decreased in lymphocytes (p<0.001). XO activity (p<0.001) and XDG activity (p<0.05) is increased in blood plasma, XO activity and XDG activity are decreased (p<0.001) in lymphocytes of patients with RF-positive RA. Plasma XO and XDG activities are also higher, and lymphocyte XO and XDG activities are lower in patients with RF-positive RA than in patients with RF-negative RA (р<0.001).Conclusion:Our study revealed the relationship between enzyme parameters and rheumatoid factor presence. More pronounced changes in the enzyme activities were observed in patients with RF-positive RA. These results demonstrate that activation of the xanthine oxidase/xanthine dehydrogenase enzyme complex is an substantial factor of induction and continuation of the autoimmune rheumatoid inflammation.Disclosure of Interests:None declared


FEBS Journal ◽  
2008 ◽  
Vol 275 (13) ◽  
pp. 3278-3289 ◽  
Author(s):  
Tomoko Nishino ◽  
Ken Okamoto ◽  
Bryan T. Eger ◽  
Emil F. Pai ◽  
Takeshi Nishino

1976 ◽  
Vol 155 (1) ◽  
pp. 81-85 ◽  
Author(s):  
D J Lowe ◽  
M J Barber ◽  
R T Pawlik ◽  
R C Bray

A new non-functional modified form of milk xanthine oxidase is described. This contains molybdenum in a quinquivalent state, which is resistant to both oxidation and reduction. The new species is derived from the native enzyme in a two-step process. The first step is the conversion into the desulpho form, via loss of the ‘persulphide’ sulphur, and the second involves reaction with ethylene glycol or other reagents. The species gives a characteristic Mo(V) electron-paramagnetic-resonance signal, without proton splittings, designated Resting II. This is virtually identical with signals reported previously from resting turkey liver xanthine dehydrogenase and rabbit liver aldehyde oxidase. The possibility is discussed that species Resting II, prepared with ethylene glycol, contains a -COCH2OH residue bound to a nitrogen ligand of molybdenum.


Author(s):  
Cristina Collazo Abal ◽  
Susana Romero Santos ◽  
Carmen González Mao ◽  
Emilio C. Pazos Lago ◽  
Francisco Barros Angueira ◽  
...  

Abstract Objectives Hereditary xanthinuria is a rare, autosomal and recessive disorder characterized by severe hypouricemia and increased xanthine excretion, caused by a deficiency of xanthine dehydrogenase/oxidase (XDH/XO, EC: 1.17.1.4/1.17.3.2) in type I, or by a deficiency of XDH/XO and aldehyde oxidase (AOX, EC: 1.2.3.1) in type II. Case presentation We describe a novel point mutation in the XDH gene in homozygosis found in a patient with very low serum and urine levels of uric acid, together with xanthinuria. He was asymptomatic but renal calculi were discovered during imaging. Additional cases were found in his family and dietary recommendations were made in order to prevent further complications. Conclusions Hereditary xanthinuria is an underdiagnosed pathology, often found in a routine analysis that shows hypouricemia. It is important for Laboratory Medicine to acknowledge how to guide clinicians in the diagnosis.


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