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Our observation that intracellular NA concentrations did not increase following NNMT inhibition extends previous studies that showed NA concentrations were largely unaffected following NNMT knockdown with either adenovirus[39] or anti-sense oligonucleotides (ASOs).[12] It is possible that significant accumulation of NA in adipocytes (and other tissues) is prevented by rapid conversion of NA to NMN and subsequent NAD + synthesis or transport to the extracellular environment.[27] Importantly, NNMT inhibition potentiated the absolute intracellular concentrations of NAD + and SAM, without altering the levels of NA and SAH in the adipocytes

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2008;29 (2 Suppl):S238-44

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Steric hindrance is the major limiting factor in the synthesis of the B 12 coenzyme analogs