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Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside meta

nmn

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#1 stefan_001

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Posted 11 January 2018 - 10:08 PM


Have not had time to really read it but it looks like an interesting study with lots of info and data points:
http://www.sciencedi...212877817303162



#2 Harkijn

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Posted 12 January 2018 - 08:14 AM

Very encouraging to see the 'jump' in NAD+levels after exogenous NR/NMN administration!



#3 Bryan_S

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Posted 26 August 2018 - 03:39 PM

Looks interesting confirms many similar studies.

 

"We originally postulated that NRK2 would be more important than NRK1 in skeletal muscle for NR salvage due to its predominant expression. However, our in vivo data and work by Ratajczak et al. showing that NRK1 controls NR and NMN metabolism in mammalian cells [28] led us to examine more closely the dependency of NR and NMN on each NRK. Using combinatorial muscle cultures of single and double NRK1/2 KO cells we confirmed that NR is exclusively metabolized by the NRK enzymes in skeletal muscle with no change to cellular NAD+ levels in DKO primary myotubes following NR supplementation, which was strikingly evident in NAD+ depleted cells. Both NRK1 and NRK2 single KO cells demonstrate a level of redundancy in their ability to respond to NR, though clearly being submaximal compared to control cells.

 

NMN is metabolized to NAD+ downstream of NRKs and NAMPT, yet exogenous NMN supplementation was unable to be metabolized to NAD+ in DKO cells, again most strikingly in the context of severe NAD+ depletion. While there is a level of redundancy in the single KO cells, the data implicate NRK1 as being more critical for regulating NMN entry into the cell. Recent findings by Ratajczak et al. have shown that NRK1 regulates exogenous NMN salvage in liver tissue and cells. They identified a requirement for NMN to be metabolized extracellularly to NR before hepatic uptake, then re-phosphorylated by NRK1 back to NMN [28]. Similar data also have highlighted that human cells can metabolize NMN to NR intracellularly utilizing cytosolic 5′-nucleotidases [40]. The data presented here in primary WT and loss-of-function myotubes corroborate these findings and reveal the NRKs critical role for both NR and NMN conversion to NAD+."


Edited by Bryan_S, 26 August 2018 - 03:45 PM.

  • Good Point x 1





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