NADase
NADase or NAD+ase (also known as NAD+ glycohydrolase) refers to a group of enzymes playing a pivotal role in cellular longevity and aging due to its direct implication in the modulation of NAD+ levels within the cell. NAD+, or Nicotinamide Adenine Dinucleotide, is a crucial coenzyme that participates in numerous metabolic and cellular processes, including energy metabolism, DNA repair, and the regulation of cellular aging. Elevated NADase activity can lead to decreased NAD+ levels, affecting cellular metabolism, reducing energy production, and potentially accelerating aging processes and age-related diseases.
Reducing NADase enzymes by corresponding inhibitors is a way to boost NAD+ levels (see NAD+ Booster).
Enzyme Reaction
NADase catalyzes the hydrolysis of NAD+, a reaction which can be represented as follows:
This reaction is pivotal as it regulates the levels of NAD+ available in the cell, directly impacting cellular energy metabolism, DNA repair mechanisms, and aging processes.
Known NADase Enzymes
Here is some information on known NADase enzymes.
| Enzyme | Description | Function | Location/Expression | Implications in Aging | Associated Diseases |
|---|---|---|---|---|---|
| CD38 | CD38 is a multifunctional enzyme involved in calcium signaling and immune response. It regulates NAD+ homeostasis by catalyzing the conversion of NAD+ to ADP-ribose and nicotinamide. | Calcium signaling, immune response, NAD+ metabolism. | Widely expressed in immune cells and various other tissues. | High activity linked to reduced NAD+ levels, impacting cellular aging and metabolic health. | Chronic inflammatory conditions, some forms of leukemia, metabolic disorders. |
| CD157 / BST1 | CD157/BST1 functions in leukocyte trafficking, particularly affecting monocyte and neutrophil migration during inflammation. It shares structural similarities with CD38 and has NADase activity. | Regulation of monocyte and neutrophil migration, inflammatory response. | Primarily found in bone marrow, myeloid cells, and certain immune cells. | Its roles in inflammation and immune regulation might impact aging-related inflammatory conditions. | Autoimmune diseases, some hematological cancers. |
| SARM1 | SARM1, crucial in programmed axon degeneration, is a central player in axonal injury responses. It possesses intrinsic NADase activity, leading to axonal degeneration. | Axonal degeneration, innate immune response. | Predominantly located in the nervous system, particularly in neurons. | Key in neurodegenerative processes related to aging and neuronal injury. | Various neurodegenerative diseases like ALS, peripheral neuropathies. |
| PARP1 | PARP1 is a DNA repair enzyme that consumes NAD+ to add ADP-ribose units to target proteins, facilitating DNA repair and cell survival. | DNA repair, cell survival, ADP-ribosylation of proteins. | Ubiquitously expressed in the nucleus of cells across various tissues. | Altered activity affects DNA repair mechanisms, crucial in aging and cellular health. | Various cancers, ischemic injuries, neurodegenerative diseases. |
| PARP2 | Similar to PARP1, PARP2 is involved in DNA repair. It also helps maintain genomic stability and regulates gene expression. | DNA repair, genomic stability, gene expression regulation. | Located in the cell nucleus, expressed in a range of cell types. | Influences DNA maintenance and repair processes important in aging. | Cancers, particularly those sensitive to DNA damage, some genetic disorders. |
| Sirtuins (SIRT1-SIRT7) | Sirtuins, a family of NAD+-dependent enzymes (SIRT1-SIRT7), are involved in a wide range of cellular processes. Each sirtuin has distinct functions, from DNA repair to metabolic regulation. | Gene expression regulation, DNA repair, metabolism, stress resistance, cell survival. | Diverse expression patterns; SIRT1, SIRT3, and SIRT6 are key in metabolic regulation. | Critical in cellular aging, metabolic health, and stress responses. | Aging, metabolic disorders, cardiovascular diseases, neurodegenerative diseases. |