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This group encompasses a diverse array of enzymes that require cofactors derived from B-complex vitamins to catalyze essential biochemical reactions. These enzymes play critical roles in central carbon metabolism, including the citric acid cycle, fatty acid oxidation, and the synthesis of nucleic acids and amino acids (StatPearls, Vitamin B Complex, 2023). For instance, enzymes like dihydrofolate reductase (DHFR) utilize folate (B9) derivatives for nucleotide biosynthesis, making them primary targets for anticancer and antimicrobial therapies (NCBI, Methotrexate, 2022). Other examples include pyridoxal phosphate (B6)-dependent transaminases involved in neurotransmitter synthesis and thiamine (B1)-dependent complexes essential for cellular energy production. Because these enzymes are fundamental to cellular viability, they are frequently exploited as therapeutic targets, particularly in oncology and infectious diseases where rapid cell proliferation or pathogen survival depends on high metabolic flux (Nature Reviews Cancer, 2020). However, targeting these enzymes requires careful management to avoid systemic toxicity, as many are expressed ubiquitously across human tissues and are vital for normal physiological function.
Drugs typically act as competitive inhibitors of the enzyme's active site or the specific cofactor binding site, thereby depleting essential metabolic intermediates or halting DNA replication and repair processes.
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