For now, we have discovered why delivering NMN causes a sharp spike in NaMN levels, which according to the textbook of NAD biology, it should not do. This also shows that the salvage pathways and Preiss-Handler / de novo pathways of NAD biosynthesis can cross over.
Why hasn't this been noticed before? In short: measurement techniques. NMN and NaMN are very similar, and hard to separately measure. To figure this out, we had to think up some neat stable isotope labelling strategies, so that we could separate NMN from newly formed NaMN.
Here, we discovered a new, neat little trick from CD38: it can convert NMN to NaMN. Rather than changing a single atom, it actually swaps out the entire nicotinamide ring of NMN, replacing it with a nicotinic acid, to form NaMN: a base-exchange, or transglycosidation reaction.
Now there are a few ways to raise NAD+ levels. One is to deliver NAD precursors such as NMN and NR, which are used to MAKE new NAD+. The other is to block the BREAKDOWN of NAD+, and one target for doing that is the cell surface enzyme CD38.
We previously found that bacteria in the gut could convert NMN to NaMN, through a "deamidation" reaction that swapped a single atom to convert between these species.
https://t.co/NLOFQGSb6d
This is one of two main pathways to NAD+ in mammals - the other is the Preiss-Handler and de novo pathways, which use the intermediate nicotinic acid mononucleotide (NaMN). Importantly, in mammals, these pathways do not cross over.
Maintaining NAD+ levels can be important during conditions of stress, such as ageing, inflammation and the side effects of chemotherapy.
For example, we showed that restoring NAD+ levels could overcome age-related infertility...
https://t.co/FbvJidAuIA
Proud to share the latest from us, out now in @jbiolchem: we find a new mechanism for crossover between the salvage and Preiss-Handler pathways of NAD+ synthesis, through a new CD38 base exchange reaction that converts NMN to NaMN.
https://t.co/ZjxN8LeyFa
New paper from us, out today: we present negative results on the impact of SIRT2 transgenic overexpression on lifespan in mice. Big thanks to collaborators and lab members past and present, and especially the lovely staff at UNSW BRC.
https://t.co/eYh9BYthpg
📣 I'm recruiting!! 📣 Open position for a postdoc in disease ecology/evolution. Do you like birds, pathogens, or genomics? Do you want to work in the Galapagos? Apply by July 1 for best consideration. Start date flexible. Contact me for info & please RT! https://t.co/pu8GB1V8mi
Congratulations to Dr @LindsayWu_UNSW, who has been awarded one of the inaugural @hevolution_f / @AFARorg New Investigator Awards in Aging Biology and Geroscience Research!
This is a cyclist using his knowledge of physics and aerodynamics to gain a competitive advantage
Michael Guerra unclips from his pedals, lies down on the seat and stretches out his legs to achieve ultimate aerodynamic efficiency.
Thousands of Sydney residents have been left without running water since Saturday, after a water main burst in Lane Cove.
Some residents have reportedly been collecting water from the road in buckets in order to flush their toilets. #9News
MORE: https://t.co/viiE9jTetc
Researchers create model #embryo in lab, using mouse stem cells, that forms a brain, beating heart, and foundations of all the other body organs https://t.co/YL61L56Y0l via @cambridge_uni