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Review
. 2024 Jul 19;14(7):869.
doi: 10.3390/biom14070869.

Molybdenum's Role as an Essential Element in Enzymes Catabolizing Redox Reactions: A Review

Jakub Piotr Adamus  1 , Anna Ruszczyńska  2 , Aleksandra Wyczałkowska-Tomasik  3
Affiliations
Review

Molybdenum's Role as an Essential Element in Enzymes Catabolizing Redox Reactions: A Review

Jakub Piotr Adamus et al. Biomolecules. .

Abstract

Molybdenum (Mo) is an essential element for human life, acting as a cofactor in various enzymes crucial for metabolic homeostasis. This review provides a comprehensive insight into the latest advances in research on molybdenum-containing enzymes and their clinical significance. One of these enzymes is xanthine oxidase (XO), which plays a pivotal role in purine catabolism, generating reactive oxygen species (ROS) capable of inducing oxidative stress and subsequent organ dysfunction. Elevated XO activity is associated with liver pathologies such as non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Aldehyde oxidases (AOs) are also molybdenum-containing enzymes that, similar to XO, participate in drug metabolism, with notable roles in the oxidation of various substrates. However, beneath its apparent efficacy, AOs' inhibition may impact drug effectiveness and contribute to liver damage induced by hepatotoxins. Another notable molybdenum-enzyme is sulfite oxidase (SOX), which catalyzes the conversion of sulfite to sulfate, crucial for the degradation of sulfur-containing amino acids. Recent research highlights SOX's potential as a diagnostic marker for HCC, offering promising sensitivity and specificity in distinguishing cancerous lesions. The newest member of molybdenum-containing enzymes is mitochondrial amidoxime-reducing component (mARC), involved in drug metabolism and detoxification reactions. Emerging evidence suggests its involvement in liver pathologies such as HCC and NAFLD, indicating its potential as a therapeutic target. Overall, understanding the roles of molybdenum-containing enzymes in human physiology and disease pathology is essential for advancing diagnostic and therapeutic strategies for various health conditions, particularly those related to liver dysfunction. Further research into the molecular mechanisms underlying these enzymes' functions could lead to novel treatments and improved patient outcomes.

Keywords: aldehyde oxidase (AO); hepatocellular carcinoma (HCC); mitochondrial amidoxime-reducing component (mARC); molybdenum (Mo); molybdenum cofactor (MoCo); molybdenum cofactor deficiency (MoCD); non-alcoholic fatty liver disease (NAFLD); sulfite oxidase (SOX); xanthine oxidase (XO).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 2
Figure 2
3D structure of bovine xanthine oxidase (XO), protein cleaved form (Animated demonstration in the Supplementary Material Figure S1) [26].
Figure 1
Figure 1
Molybdenum cofactor (MoCo) molecule in 2D projection. The colors and corresponding atoms are as follows: yellow (sulfur; S) dark grey (carbon; C), navy (nitrogen; N), red (oxygen; O), light grey (hydrogen; H), orange (phosphorus; P), turquoise (molybdenum; Mo). The aforementioned colors are used throughout the remaining 2D figures.
Figure 3
Figure 3
Selected reactions catalyzed by xanthine oxidase (XO), with pictures of hypoxanthine, xanthine, and uric acid molecules.
Figure 4
Figure 4
3D structure of human aldehyde oxidase (AO) protein (Animated demonstration in the Supplementary Material Figure S2) [52].
Figure 5
Figure 5
6-mercaptopurine (6MP) conversion into 6-thixanthine (6TX) intermediate, which is transformed into 6-thiouric acid (6TUA).
Figure 6
Figure 6
3D structure of recombinant chicken sulfite oxidase (SOX) protein at resting state (Animated demonstration in the Supplementary Material Figure S3) [61].
Figure 7
Figure 7
3D structure of mitochondrial amidoxime-reducing component 1 (mARC1) protein (Animated demonstration in the Supplementary Material Figure S4) [85].
Figure 8
Figure 8
Selected mARC substrates.
See this image and copyright information in PMC

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