Description
NAD⁺ (Bio-Fermented) – Advanced Biochemical Mechanism Profile
(Oxidized Nicotinamide Adenine Dinucleotide; Redox Cofactor; Sirtuin/Substrate for PARP Enzymes)
NAD⁺ is a central pyridine nucleotide cofactor that participates in oxidation–reduction reactions and functions as a required substrate for sirtuin deacetylases, PARP family enzymes, CD38/CD157 ectoenzymes, and several dehydrogenases involved in cellular metabolism.
✅ 1. Core Biochemical Function
Redox Cofactor (Electron Carrier)
NAD⁺ ⇌ NADH cycling drives electron transfer in:
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Complex I of the electron transport chain
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Glycolysis (GAPDH)
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TCA cycle (IDH3, MDH2, α-KGDH)
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β-oxidation (ACAD family enzymes)
This supports ATP generation through:
NADH → ETC → proton gradient → ATP synthase → oxidative phosphorylation
✅ 2. Primary Enzyme Targets
A. Sirtuins (SIRT1–SIRT7) – NAD⁺‐Dependent Deacetylases
NAD⁺ is consumed as a substrate during sirtuin-mediated protein deacetylation:
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Alters histones and transcription factors
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Regulates mitochondrial biogenesis and metabolic genes
Key downstream targets:
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PGC-1α, FOXO1/3, p53, NF-κB (RelA/p65)
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Enhanced mitochondrial oxidative capacity via PPARGC1A → NRF1/TFAM transcription
B. PARP Enzymes (Poly-ADP Ribose Polymerases)
NAD⁺ donates ADP-ribose for DNA repair signaling:
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PARP-1 / PARP-2 activation at DNA strand breaks
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Recruitment of XRCC1, POLβ, and LIG3
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Supports base-excision repair (BER)
Excessive PARP activity consumes NAD⁺ → influences cellular energy balance.
C. CD38 / CD157 (Ecto-enzymes)
Convert NAD⁺ → cyclic ADP-ribose and NAADP
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Regulate Ca²⁺ signaling in intracellular stores
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Influence mitochondrial Ca²⁺ dynamics and metabolic flux
✅ 3. Major Pathway Effects
1) NAD⁺ → SIRT1 → PGC-1α → Mitochondrial Biogenesis
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↑ PGC-1α deacetylation
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Upregulates NRF1, NRF2, TFAM
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Promotes mitochondrial DNA replication and oxidative capacity
2) NAD⁺ → SIRT3 → Mitochondrial Enzyme Deacetylation
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SOD2 (MnSOD) activation → ROS reduction
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IDH2, LCAD, ACADL → enhanced fatty acid oxidation
3) NAD⁺ → PARP-1 → DNA Repair
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ADP-ribosylation of chromatin and repair factors
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Maintenance of genomic stability
4) NAD⁺ → CD38/CD157 → cADPR signaling
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Modulates ryanodine receptors and Ca²⁺ release
✅ 4. Second Messengers & Metabolic Outputs
| Molecule | Effect |
|---|---|
| NADH | Donates electrons to ETC (Complex I) |
| cADPR / NAADP | Ca²⁺ release from ER/lysosomal stores |
| Acetyl-CoA flux | Regulated by SIRT-mediated enzyme deacetylation |
| AMPK activation (indirect) | Via improved mitochondrial efficiency |
✅ 5. Gene Targets Commonly Measured in Research
| Category | Example Genes |
|---|---|
| Mitochondrial Biogenesis | PPARGC1A, NRF1, TFAM |
| Antioxidant Response | SOD2, CAT, GPX1 |
| Metabolic Regulation | PGC-1α, CPT1B, PPAR-α |
| DNA Repair | PARP1, XRCC1, LIG3, POLB |
| Stress Resistance | FOXO1, FOXO3, SIRT1 |
✅ Summary of Mechanistic Features
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Central redox cofactor in oxidative phosphorylation
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Essential substrate for sirtuins, PARP enzymes, and CD38
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Regulates mitochondrial biogenesis, DNA repair, Ca²⁺ signaling
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Modulates transcription of metabolic and antioxidant genes
Research-Only Use Classification
Bio-fermented NAD⁺ is supplied solely for laboratory in-vitro research.
Not approved for human or animal administration, therapeutic use, or any biological application outside controlled research settings.
