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:

${\text{NAD}}^{+}+{\text{H}}_{2}{\text{O}}\xrightarrow {\text{NADase}} {\text{Nicotinamide}}+{\text{ADP-ribose}}$

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.

See also

• Nicotinamide Adenine Dinucleotide (NAD)
• NAD+ Boosters
• Sirtuins
• Wikipedia - NAD+ glycohydrolase