Abstract
- Background
Four molybdenum-dependent enzymes are known in humans, each harboring a pterin-based molybdenum cofactor ($\text{Moco}$) in the active site. These enzymes catalyze key redox reactions using water as an oxygen acceptor or donor. $\text{Moco}$ is synthesized through an evolutionary conserved biosynthetic pathway, and its deficiency results in a severe inborn error of metabolism that frequently leads to early childhood death.
- Methods
This review synthesizes current knowledge on the biosynthesis of $\text{Moco}$, key structural and functional features of human molybdenum-dependent enzymes, and the clinical focus on $\text{Moco}$ deficiency. Pathophysiological disease mechanisms, the roles of specific enzymatic losses, diagnostic biomarkers, and current therapeutic strategies were comprehensively evaluated.
- Results
Disease-causing symptoms in $\text{Moco}$ deficiency primarily stem from the loss of sulfite oxidase ($\text{SO}$) activity, a critical enzyme in cysteine catabolism whose absence leads to toxic accumulation of sulfite and severe neurodegeneration. In addition to their classic catalytic functions, human molybdenum-enzymes have recently been recognized for novel biological roles, including the reduction of nitrite to nitric oxide. Advances in understanding the biosynthetic pathway have enabled targeted treatment strategies, such as substitution therapy for specific genetic subtypes.
- Conclusions
Moco is indispensable for human metabolic homeostasis and neurodevelopment. Understanding the molecular mechanisms of Moco deficiency and early recognition of sulfite toxicity are critical for applying targeted life-saving therapies.
https://pubmed.ncbi.nlm.nih.gov/27055119/