Key Pointers
- Energy production for the cell.
- Muscle regeneration and development.
- Aging and cell death.
The human body consists of 37.2 trillion cells. These cells need NAD+ to maintain their functions and fulfil energy requirements. We take vitamin B3 from different food sources and supplements that meet our NAD+ needs. Modern research shows that deficiency of NAD in the body leads to various chronic diseases and age-related disorders.
NAD+ has a significant role in the energy production process of the cell through cellular respiration. It takes part in hundreds of chemical reactions in the body. We ingest different forms of foods that are ultimately converted to sugar in the cells. Some cells like the brain and red blood cells, convert this sugar into simple sugar such as glucose to achieve their energy prerequisites.
The breakdown of fats or amino acids occurs in the cell to perform multiple functions including energy production, in which the energy is transferred to NAD+ and converts NAD+ into NADH. This reduced form of NAD+ plays a role in energy production in the form of ATP through the electron transport chain.
Muscles are an integral part of the body and perform numerous functions. Skeletal muscles are massive in the body and major consumers of fatty acids and glucose. The metabolism of fatty acids and glucose in skeletal muscles requires NAD+. Thus it has a pivotal role in energy production. It takes part in muscle regeneration, development, and homeostasis by influencing many cellular processes, including the organisation of extracellular matrix, transcription, and biogenesis of mitochondria.
NAD+ is thought to have a role in the lifespan and lifespan of living things, including humans. The ratio of the NAD+/NADH declines with advancing age and is also related to senile changes such as mitochondrial dysfunction. The dietary deficiency of NAD+ causes pellagra, a disease with neurodegenerative, skin, and psychological symptoms. Modern research shows that an augmented level of NAD+ in the womb is related to an increased life span. The activity of NAD+ enzymes also declines with a decrease of NAD+ levels in the body. Sirtuins are deacetylases that depend upon NAD+ for their activity. Sirtuins take part in many important functions, including DNA repair, protein metabolism, stress response, and chromatin remodelling. Due to these essential functions, NAD+ is considered to be the regulator of the aging process.
NAD is also found in the extracellular matrix and plays an important role in performing several biological functions. NAD acts as a ligand for many purine receptors and binds to purinergic receptor P2Y11. It finally causes the activation of the proliferation and migration response of the cell.
Necrosis is an uncontrolled division of cells that leads to cell death. On the other hand, necroptosis is a controlled division of the cell. The NAD+ has a pivotal role in the regulation of necroptosis. It is not considered to be an authentic survivor of the cell but helps in the regulation of this process of cell division.
Conclusion
The role of NAD+ is essential for life as it takes part in the basic pathway of energy production in the cell through the electron transport chain. NAD+ also plays a key role in muscle, development, and regeneration. Its deficiency is related to different chronic illnesses like neurodegenerative diseases and diabetes. Its role as a regulator in aging and cell death is versatile and still a topic of great interest for future study.
References
- Agledal L, Niere M, and Ziegler M. The phosphate makes a difference: Cellular functions of NADP. Redox Rep 15: 2–10, 2010 [PMC free article] [PubMed].
- Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, and Finkel T. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci U S A 105: 14447–14452, 2008.
- Canto C, Menzies KJ, and Auwerx J. NAD(+) metabolism and the control of energy homeostasis: A balancing act between mitochondria and the nucleus. Cell Metab 22: 31–53, 2015