Nicotinic acid adenine dinucleotide phosphate

NAADP Overview

NAADP metabolism

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Ca Storage

Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) is a cell signaling molecule involved in various biological processes within cells. It is considered one of the most potent calcium-mobilizing agents, playing a crucial role in the release of calcium from intracellular stores. NAADP is unique among the nucleotides involved in calcium signaling, such as inositol 1,4,5-trisphosphate (IP3) and cyclic ADP-ribose (cADPR), due to its distinct mode of action and the calcium stores it targets.

Biosynthesis and Structure

NAADP is synthesized from NADP+ through the addition of nicotinic acid, facilitated by specific enzymes. Its structure comprises two nucleotides linked by a phosphate group: nicotinic acid and adenine dinucleotide phosphate. This unique structure is essential for its role in calcium signaling.

Mechanism of Action

The primary function of NAADP is to mobilize calcium from intracellular stores, notably from acidic organelles such as lysosomes and endolysosomes, which is distinct from the calcium release mediated by IP3 and cADPR from the endoplasmic reticulum. NAADP binds to and activates specific calcium channels on these organelles, leading to a rapid increase in intracellular calcium levels. This increase in calcium concentration can then activate various cellular processes.

Physiological Roles

NAADP plays a significant role in a variety of physiological processes, including:

• Muscle contraction
• Insulin secretion
• Fertilization
• Neurotransmission
• Immune response

Its involvement in these processes highlights the importance of NAADP in maintaining cellular and physiological homeostasis.

Pathophysiology

Given its critical role in calcium signaling, dysregulation of NAADP levels or its signaling pathways can contribute to the pathogenesis of several diseases, such as:

• Diabetes mellitus
• Cardiovascular diseases
• Neurodegenerative diseases

Understanding the mechanisms of NAADP action and its involvement in disease processes is crucial for developing therapeutic strategies targeting calcium signaling pathways.

Research and Therapeutic Potential

Research on NAADP has expanded our understanding of calcium signaling and its implications in health and disease. The development of specific inhibitors and activators of NAADP signaling pathways holds potential for therapeutic applications in treating diseases associated with dysregulated calcium signaling.