What are the potential implications of entecavir (ETV) inhibiting deoxyguanosine kinase (dGK) in mitochondrial DNA (mtDNA) synthesis?

Label:chem

Topic
Mitochondrial DNA (mtDNA) depletion syndromes (MDSs) are associated with deficiencies in mitochondrial kinases like dGK. These syndromes often result in severe clinical outcomes due to impaired mtDNA synthesis.
Answer
ETV's inhibition of dGK could lead to reduced levels of deoxyguanosine triphosphate (dGTP) and deoxyadenosine triphosphate (dATP), potentially causing imbalances in deoxynucleotide pools. This imbalance may lead to mtDNA depletion, as seen in dGK deficiency syndromes, and could contribute to mitochondrial toxicity observed in long-term ETV treatment.
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