NAD+NAD+ Too Big to Enter Cell?

drkris69
Posts: 843
Joined: Tue Aug 20, 2019 2:41 pm

Re: NAD+ Too Big to Enter Cell?

Post by drkris69 » Tue Feb 18, 2020 3:45 pm

Okay thanks Boxcast, I will check this out while doing my 1.5 hrs of cardio tonight. I love getting turned onto new channels on youtube. Thanks again. :)


Drdavid
Posts: 735
Joined: Thu Aug 15, 2019 9:59 am

Re: NAD+ Too Big to Enter Cell?

Post by Drdavid » Wed Feb 19, 2020 6:26 am

Thank you for the link to new information
Newage
Posts: 1190
Joined: Thu Aug 22, 2019 10:22 pm

Re: NAD+ Too Big to Enter Cell?

Post by Newage » Wed Feb 19, 2020 2:05 pm

Boxcost wrote:
Tue Feb 18, 2020 2:46 pm
drkris69 wrote:
Tue Feb 18, 2020 9:52 am
It will be nice when we have a way to measure NAD levels in the blood just to make sure we are at optimal levels. Is there a blood test (panel) out there now? I dont think so not as of yet.
Check this out, interview with James Clement on mTOR and Autophagy
https://www.youtube.com/watch?v=n9SQjWxWMkE&fbclid=

At about 54min (then for about 20min) they start discussing NAD - James is building / tuning a mass spectrometer to test levels in humans!
Thanks Boxcost.
It will answer a lot of the questions concerning uptake when we can eventually measure NAD+ levels whether it by taking precursors or NAD+ itself. As I assume everyone’s uptake will be different it would be nice to know how much of the molecule or precursor we should take to receive optimal results without wastage..
Drdavid
Posts: 735
Joined: Thu Aug 15, 2019 9:59 am

Re: NAD+ Too Big to Enter Cell?

Post by Drdavid » Fri Feb 21, 2020 6:58 am

Newage wrote:
Wed Feb 19, 2020 2:05 pm
Boxcost wrote:
Tue Feb 18, 2020 2:46 pm
drkris69 wrote:
Tue Feb 18, 2020 9:52 am
It will be nice when we have a way to measure NAD levels in the blood just to make sure we are at optimal levels. Is there a blood test (panel) out there now? I dont think so not as of yet.
Check this out, interview with James Clement on mTOR and Autophagy
https://www.youtube.com/watch?v=n9SQjWxWMkE&fbclid=

At about 54min (then for about 20min) they start discussing NAD - James is building / tuning a mass spectrometer to test levels in humans!
Thanks Boxcost.
It will answer a lot of the questions concerning uptake when we can eventually measure NAD+ levels whether it by taking precursors or NAD+ itself. As I assume everyone’s uptake will be different it would be nice to know how much of the molecule or precursor we should take to receive optimal results without wastage..
Your assumption would be correct. We are all different and some will metabolize quicker others slower. This makes a difference in dosing and that is why individual plans are important.
Drdavid
Posts: 735
Joined: Thu Aug 15, 2019 9:59 am

Re: NAD+ Too Big to Enter Cell?

Post by Drdavid » Fri Feb 21, 2020 6:58 am

Newage wrote:
Wed Feb 19, 2020 2:05 pm
Boxcost wrote:
Tue Feb 18, 2020 2:46 pm
drkris69 wrote:
Tue Feb 18, 2020 9:52 am
It will be nice when we have a way to measure NAD levels in the blood just to make sure we are at optimal levels. Is there a blood test (panel) out there now? I dont think so not as of yet.
Check this out, interview with James Clement on mTOR and Autophagy
https://www.youtube.com/watch?v=n9SQjWxWMkE&fbclid=

At about 54min (then for about 20min) they start discussing NAD - James is building / tuning a mass spectrometer to test levels in humans!
Thanks Boxcost.
It will answer a lot of the questions concerning uptake when we can eventually measure NAD+ levels whether it by taking precursors or NAD+ itself. As I assume everyone’s uptake will be different it would be nice to know how much of the molecule or precursor we should take to receive optimal results without wastage..
Your assumption would be correct. We are all different and some will metabolize quicker others slower. This makes a difference in dosing and that is why individual plans are important.
NewLifeScience
Posts: 416
Joined: Thu Aug 22, 2019 4:17 pm

Re: NAD+ Too Big to Enter Cell?

Post by NewLifeScience » Sun Feb 23, 2020 1:07 pm

So yup, I have seen the research that in can cross the membrane of many cells.

And anecdotally, i can feet it working with my metabolism.
NMN

Astragalus
Berberine
Blueberry extract
Green Tea Extract
Gotu Kola
Liposomal Curcumin / Resveratrol
Melatonin
Methyl B12
Methylfolate
Sulforaphane
Vitamin C
Vitamin D
Vitamin E tocotrienols
Vitamin K2
Virgin Olive Oil
Moyvore
Posts: 1
Joined: Mon Sep 16, 2019 8:38 pm

Re: NAD+ Too Big to Enter Cell?

Post by Moyvore » Tue Sep 15, 2020 12:29 am

looks like a race between two research groups for first publication:

Luongo, T.S., Eller, J.M., Lu, M. et al.  Nature (Published: 09 September 2020).
https://doi.org/10.1038/s41586-020-2741-7

SLC25A51 is a mammalian mitochondrial NAD+ transporter

Mitochondria require nicotinamide adenine dinucleotide (NAD+) in order to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD+ transporters have been identified in yeast and plants1,2 but their very existence is controversial in mammals3–5. Here we demonstrate that mammalian mitochondria are capable of taking up intact NAD+ and identify SLC25A51 (an essential6,7 mitochondrial protein of previously unknown function, also known as MCART1) as a mammalian mitochondrial NAD+ transporter. Loss of SLC25A51 decreases mitochondrial but not whole-cell NAD+ content, impairs mitochondrial respiration, and blocks the uptake of NAD+ into isolated mitochondria. Conversely, overexpression of SLC25A51 or a nearly identical paralog, SLC25A52, increases mitochondrial NAD+ levels and restores NAD+

Posted in Science Advances, also on 09 September 2020

Nora Kory, Jelmi uit de Bos, et al:

MCART1/SLC25A51 is required for mitochondrial NAD transport

The nicotinamide adenine dinucleotide (NAD+/NADH) pair is a cofactor in redox reactions and is particularly critical in mitochondria as it connects substrate oxidation by the tricarboxylic acid (TCA) cycle to ATP generation by the electron transport chain (ETC) and oxidative phosphorylation. While a mitochondrial NAD+ transporter has been identified in yeast, how NAD enters mitochondria in metazoans is unknown. Here, we mine gene essentiality data from human cell lines to identify MCART1 (SLC25A51) as co-essential with ETC components. MCART1-null cells have large decreases in TCA cycle flux, mitochondrial respiration, ETC complex I activity, and mitochondrial levels of NAD+ and NADH. Isolated mitochondria from cells lacking or overexpressing MCART1 have greatly decreased or increased NAD uptake in vitro, respectively. Moreover, MCART1 and NDT1, a yeast mitochondrial NAD+ transporter, can functionally complement for each other. Thus, we propose that MCART1 is the long sought mitochondrial transporter for NAD in human cells

https://advances.sciencemag.org/content ... /tab-pdfHo

Also published as a preprint in biorxiv on August 28, 2020:

https://www.biorxiv.org/content/10.1101 ... 1.abstract

With a lot of tweeted comments on this paper by other researchers.
 
Drdavid
Posts: 735
Joined: Thu Aug 15, 2019 9:59 am

Re: NAD+ Too Big to Enter Cell?

Post by Drdavid » Wed Sep 30, 2020 7:44 pm

Very interesting research and both of these will be published.  We should see even more this next year.
drkris69
Posts: 843
Joined: Tue Aug 20, 2019 2:41 pm

Re: NAD+ Too Big to Enter Cell?

Post by drkris69 » Thu Oct 01, 2020 11:08 am

Moyvore wrote:
Tue Sep 15, 2020 12:29 am
looks like a race between two research groups for first publication:

Luongo, T.S., Eller, J.M., Lu, M. et al.  Nature (Published: 09 September 2020).
https://doi.org/10.1038/s41586-020-2741-7

SLC25A51 is a mammalian mitochondrial NAD+ transporter

Mitochondria require nicotinamide adenine dinucleotide (NAD+) in order to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD+ transporters have been identified in yeast and plants1,2 but their very existence is controversial in mammals3–5. Here we demonstrate that mammalian mitochondria are capable of taking up intact NAD+ and identify SLC25A51 (an essential6,7 mitochondrial protein of previously unknown function, also known as MCART1) as a mammalian mitochondrial NAD+ transporter. Loss of SLC25A51 decreases mitochondrial but not whole-cell NAD+ content, impairs mitochondrial respiration, and blocks the uptake of NAD+ into isolated mitochondria. Conversely, overexpression of SLC25A51 or a nearly identical paralog, SLC25A52, increases mitochondrial NAD+ levels and restores NAD+

Posted in Science Advances, also on 09 September 2020

Nora Kory, Jelmi uit de Bos, et al:

MCART1/SLC25A51 is required for mitochondrial NAD transport

The nicotinamide adenine dinucleotide (NAD+/NADH) pair is a cofactor in redox reactions and is particularly critical in mitochondria as it connects substrate oxidation by the tricarboxylic acid (TCA) cycle to ATP generation by the electron transport chain (ETC) and oxidative phosphorylation. While a mitochondrial NAD+ transporter has been identified in yeast, how NAD enters mitochondria in metazoans is unknown. Here, we mine gene essentiality data from human cell lines to identify MCART1 (SLC25A51) as co-essential with ETC components. MCART1-null cells have large decreases in TCA cycle flux, mitochondrial respiration, ETC complex I activity, and mitochondrial levels of NAD+ and NADH. Isolated mitochondria from cells lacking or overexpressing MCART1 have greatly decreased or increased NAD uptake in vitro, respectively. Moreover, MCART1 and NDT1, a yeast mitochondrial NAD+ transporter, can functionally complement for each other. Thus, we propose that MCART1 is the long sought mitochondrial transporter for NAD in human cells

https://advances.sciencemag.org/content ... /tab-pdfHo

Also published as a preprint in biorxiv on August 28, 2020:

https://www.biorxiv.org/content/10.1101 ... 1.abstract

With a lot of tweeted comments on this paper by other researchers.
 

 
Very cool thank you.
 
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