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 plays a role in immune response, cellular metabolism, and NAD+ homeostasis. | Calcium signaling, cell adhesion, immune response. | Widely expressed in various tissues, including immune cells. | Involved in cellular aging processes, and its activity has been linked to a reduction in cellular NAD+ levels. | Chronic inflammatory conditions, some leukemias |
| CD157 / BST1 | CD157, also known as bone marrow stromal antigen 1 (BST1), is involved in monocyte and neutrophil infiltration during inflammatory responses and has implications in leukocyte trafficking. | Monocyte and neutrophil infiltration during inflammatory responses. | Primarily expressed in bone marrow and myeloid cells. | Its roles in inflammation might have implications in aging-related inflammatory conditions. | Autoimmune diseases, some cancers |
| SARM1 | SARM1 (Sterile Alpha and TIR Motif Containing 1) is predominantly known for its role in programmed axon degeneration and has implications in neurodegenerative conditions. | Induces axonal degeneration after injury, involved in innate immune response. | Predominantly expressed in the nervous system. | Its role in axon degeneration has implications in aging-related neurodegenerative conditions. | Neurodegenerative diseases |
| PARP1 | PARP1 (Poly ADP-Ribose Polymerase 1) is involved in DNA repair and cell death. It uses NAD+ to add ADP-ribose units to proteins. | DNA repair, modification of nuclear proteins, cell death. | Expressed in the nucleus of cells, widespread in various tissues. | Altered PARP1 activity can influence aging processes, particularly in DNA repair mechanisms. | Cancer, neurodegenerative diseases, inflammatory diseases |
| PARP2 | PARP2, similar to PARP1, participates in DNA repair and can modify proteins through ADP-ribosylation. It also plays a role in maintaining genomic stability. | DNA repair, genomic stability, ADP-ribosylation of proteins. | Found in the nucleus, expressed in various cell types. | Influences aging-related processes, especially in DNA maintenance and repair. | Cancer, certain genetic disorders |
| Sirtuins | Sirtuins, a family of NAD+-dependent deacetylases, are involved in various cellular processes like aging, gene expression regulation, and stress resistance. Some also have ADP-ribosyltransferase activity. | Regulation of gene expression, DNA repair, metabolism, stress resistance. | Widely expressed in various tissues; different sirtuins have specific distributions. | Play a critical role in aging and longevity, influencing various age-related cellular processes. | Aging-related diseases, metabolic disorders, neurodegenerative diseases |