Research summary
NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy.
Biochimica et biophysica acta 2016
Cellular metabolism review
NAD+ connects metabolism with signalling in two ways: it cycles with NADH in redox reactions and is consumed by enzymes such as sirtuins, PARPs and CD38. De-novo and salvage pathways replenish the available pools. This biochemical framework explains why concentration, synthesis and consumption need separate measurements.
View on PubMed: NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy.Metabolic control by sirtuins and other enzymes that sense NAD(+), NADH, or their ratio.
Biochimica et biophysica acta. Bioenergetics 2017
Cellular NAD biology review
Sirtuins respond to NAD+ availability differently from enzymes that sense NADH or the NAD+:NADH ratio. The biochemical evidence reviewed supports NAD+ sensing by sirtuins, rather than direct sensing of NADH or the ratio in the same way. This distinction separates redox balance from the supply of a consumed enzyme substrate.
View on PubMed: Metabolic control by sirtuins and other enzymes that sense NAD(+), NADH, or their ratio.Cellular Compartmentation and the Redox/Nonredox Functions of NAD().
Antioxidants & redox signaling 2019
Cellular NAD homeostasis review
NAD-dependent reactions operate in distinct mitochondrial, cytosolic and nuclear environments. Local cofactor concentrations and enzyme abundance can make a change important in one compartment but less relevant in another. This explains why a bulk cellular NAD measurement does not describe every redox or signalling reaction equally.
View on PubMed: Cellular Compartmentation and the Redox/Nonredox Functions of NAD().Quantitative Analysis of NAD Synthesis-Breakdown Fluxes.
Cell metabolism 2018
Cellular and animal mechanistic research
Isotope tracing revealed substantial differences in NAD synthesis and consumption between tissues. Cell lines relied on nicotinamide and consumed NAD through pathways including PARPs and sirtuins, while liver-derived nicotinamide supported wider tissue metabolism. Measuring turnover therefore gives information that a single NAD concentration cannot provide.
View on PubMed: Quantitative Analysis of NAD Synthesis-Breakdown Fluxes.Models studied
- NAD+/NADH electron transfer
- Cellular energy metabolism
- NAD-dependent enzyme activity
- NAD biosynthetic pathways
Key findings
Redox and consumption pathways
Redox cycling and enzymatic consumption draw on NAD through different chemical processes.
Sirtuin sensing versus redox balance
Sirtuin substrate availability is not interchangeable with sensing the NAD+:NADH redox ratio.
Why cellular compartments matter
Compartment-specific concentrations and enzymes qualify the meaning of a bulk NAD measurement.
Synthesis and consumption flux
Flux measurements reveal tissue differences in synthesis and consumption that concentration alone can miss.
References
NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy.
Biochimica et biophysica acta 2016
PMID 27374990
View on PubMed: NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy.Metabolic control by sirtuins and other enzymes that sense NAD(+), NADH, or their ratio.
Biochimica et biophysica acta. Bioenergetics 2017
PMID 28947253
View on PubMed: Metabolic control by sirtuins and other enzymes that sense NAD(+), NADH, or their ratio.Cellular Compartmentation and the Redox/Nonredox Functions of NAD().
Antioxidants & redox signaling 2019
PMID 30784294
View on PubMed: Cellular Compartmentation and the Redox/Nonredox Functions of NAD().Quantitative Analysis of NAD Synthesis-Breakdown Fluxes.
Cell metabolism 2018
PMID 29685734
View on PubMed: Quantitative Analysis of NAD Synthesis-Breakdown Fluxes.
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