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Nicotinamide Mononucleotide (NMN): Difference between revisions
Nicotinamide Mononucleotide (NMN) (view source)
Revision as of 17:40, 2 December 2023
, 2 December 2023→Controversy about NMN as Direct Precursor
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NMN is often advertised, for example by NMN suppliers, as a direct precursor to NAD+, purportedly making it more effective compared to other precursors like '''Nicotinamide Riboside (NR)'''. However, NMN's role as a direct precursor is only effective when it is '''inside the cell'''. This raises questions about how NMN, when ingested or administered externally, enters the cell to contribute to NAD+ synthesis. The central controversy surrounding NMN as a precursor to NAD+ lies in its mechanism of cellular entry. While NMN is a direct precursor of NAD+ within the cell, the debate focuses on whether NMN can be directly absorbed by cells or if it must first be converted to NR. In that case, NR might have an advantage over NMN, as NMN would require one additional conversion step compared to NR. | NMN is often advertised, for example by NMN suppliers, as a direct precursor to NAD+, purportedly making it more effective compared to other precursors like '''Nicotinamide Riboside (NR)'''. However, NMN's role as a direct precursor is only effective when it is '''inside the cell'''. This raises questions about how NMN, when ingested or administered externally, enters the cell to contribute to NAD+ synthesis. The central controversy surrounding NMN as a precursor to NAD+ lies in its mechanism of cellular entry. While NMN is a direct precursor of NAD+ within the cell, the debate focuses on whether NMN can be directly absorbed by cells or if it must first be converted to NR. In that case, NR might have an advantage over NMN, as NMN would require one additional conversion step compared to NR. | ||
# '''Direct Transport Mechanism''': One hypothesis suggests that NMN can directly enter cells through specific transporters. The ''Slc12a8'' transporter in the aged mouse ileum has been suggested to facilitate NMN's direct absorption{{pmid|31131364}}. However, this idea has faced challenges due to conflicting research findings{{pmid|32694648}}{{pmid|27725675}}, and the functionality of | # '''Direct Transport Mechanism''': One hypothesis suggests that NMN can directly enter cells through specific transporters. The '''Slc12a8''' transporter in the aged mouse ileum has been suggested to facilitate NMN's direct absorption{{pmid|31131364}}. However, this idea has faced challenges due to conflicting research findings{{pmid|32694648}}{{pmid|27725675}}, and the functionality of Slc12a8 in humans has yet to be conclusively determined. | ||
# '''Dephosphorylation to NR:''' An alternative and currently more widely accepted theory proposes that NMN is not directly utilized by cells. Instead, it is first converted to '''Nicotinamide Riboside (NR)''' through dephosphorylation before cellular absorption. This conversion is mediated by enzymes like CD73. Once inside the cell as NR, it is then phosphorylated into NMN{{pmid|27725675}}{{pmid|32389638}}. | # '''Dephosphorylation to NR:''' An alternative and currently more widely accepted theory proposes that NMN is not directly utilized by cells. Instead, it is first converted to '''Nicotinamide Riboside (NR)''' through dephosphorylation before cellular absorption. This conversion is mediated by enzymes like CD73. Once inside the cell as NR, it is then phosphorylated into NMN{{pmid|27725675}}{{pmid|32389638}}. | ||
While direct transportation into the cell and dephosphorylation to NR can coexists, studies indicate that orally ingested NMN is predominantly converted to NR in the intestinal tissue before absorption, challenging the view of NMN as a direct precursor to NAD+{{pmid|37463842}}. | While direct transportation into the cell and dephosphorylation to NR can coexists, studies in mice indicate that orally ingested NMN is predominantly converted to NR in the intestinal tissue before absorption, challenging the view of NMN as a direct precursor to NAD+{{pmid|37463842}}. | ||
==Potential Benefits== | ==Potential Benefits== | ||