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This particular form represents the most reduced and chemically reactive state of cobalamin, rendering it highly receptive to binding a methyl group from a form of vitamin B9 called 5-methyltetrahydrofolate, the product of methylenetetrahydrofolate reductase (MTHFR), to generate methylcobalamin (MeCbl)

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In contrast, the 2,3-diamino substitution in the 1MQ scaffold (2,3-diamino-1MQ) displayed high passive permeability (Table 1), but moderate bi-directional active transport with moderate efflux ratio (Table 2)

This inhibition preserves cellular NAD+ levels by reducing their consumption, simultaneously increasing GLUT4 transporter expression and activating sirtuin 1, known as the "longevity gene." The compound exhibits high membrane permeability and selectivity without affecting related methyltransferases or NAD+ salvage pathway enzymes, creating targeted metabolic effects while maintaining cellular safety