How is Niacin Converted to NAD? The Preiss-Handler Pathway Explained

December 24, 2025 •

3 min read

Over 500 different enzymatic tasks in the body require the coenzyme NAD+. Understanding how is niacin converted to NAD+ is key to comprehending cellular energy and metabolic regulation, as this intricate process is one of the primary ways our body synthesizes this critical molecule.

Quick Summary

Niacin is converted into the vital coenzyme NAD+ through the Preiss-Handler pathway, a multi-step enzymatic process. This mechanism involves several key intermediaries and enzymes, ensuring cells can produce and maintain adequate NAD+ levels necessary for energy metabolism and cellular health.

Key Points

Preiss-Handler Pathway: This is the primary pathway for converting niacin (nicotinic acid) into NAD+.
Three-Step Enzymatic Process: The pathway involves three key steps: phosphoribosylation, adenylylation, and amidation, with specific enzymes facilitating each reaction.
NAMN Intermediate: Nicotinic acid mononucleotide (NAMN) is a key intermediate molecule in the conversion process, which is also a shared intermediate with the de novo synthesis pathway from tryptophan.
NMNAT Enzymes: The NMNAT family of enzymes are crucial for the second step, adenylylation, converting NAMN to NAAD.
High Efficiency: Compared to synthesis from tryptophan, the Preiss-Handler pathway from niacin is a much more efficient way for most cells to generate NAD+.
Factors Affecting Conversion: The conversion rate is influenced by several factors, including the activity of pathway enzymes like NAPRT, overall ATP availability, and adequate levels of B vitamins and minerals.

Unveiling the Conversion: The Preiss-Handler Pathway

The conversion of niacin (nicotinic acid, or NA) into nicotinamide adenine dinucleotide (NAD+) is accomplished through a specific salvage pathway known as the Preiss-Handler pathway. This metabolic route is vital for maintaining the body's NAD+ pool, which is essential for countless cellular functions, including energy production, DNA repair, and gene expression regulation. Unlike the de novo pathway, which starts from the amino acid tryptophan, the Preiss-Handler pathway directly utilizes dietary niacin, making it a more efficient route for NAD+ synthesis in most mammalian tissues outside the liver.

Step-by-Step Breakdown of the Preiss-Handler Pathway

This intricate process can be broken down into three main enzymatic steps:

Phosphoribosylation: The journey begins with the enzyme nicotinate phosphoribosyltransferase (NAPRT). This enzyme catalyzes the conversion of niacin and a molecule called 5-phosphoribosyl-1-pyrophosphate (PRPP) into nicotinic acid mononucleotide (NAMN). The NAPRT-catalyzed step is considered the rate-limiting step of the Preiss-Handler pathway, controlling the overall flux of niacin into NAD+.
Adenylylation: Next, NAMN is converted into nicotinic acid adenine dinucleotide (NAAD). This reaction is mediated by a family of enzymes called nicotinate/nicotinamide mononucleotide adenylyltransferases (NMNATs). Adenylylation involves the transfer of an adenylate moiety from ATP to NAMN, consuming cellular energy in the process.
Amidation: The final step involves the conversion of NAAD to NAD+. This is achieved by the enzyme NAD+ synthetase (NADSYN), which uses glutamine as a nitrogen source to aminate the nicotinic acid group. The completion of this step yields the final, active coenzyme, NAD+.

The Importance of the Salvage and De Novo Pathways

It is crucial to understand that the body has multiple pathways for synthesizing NAD+, providing a robust and flexible system for maintaining cellular health. While the Preiss-Handler pathway uses dietary niacin, the salvage pathway is primarily responsible for recycling nicotinamide (NAM), a byproduct of NAD+-consuming reactions. Both these mechanisms are more efficient and energetically favorable than the de novo pathway from tryptophan.

Factors Influencing the Conversion Rate

Several factors can influence the efficiency of niacin's conversion to NAD+:

Enzyme Levels and Activity: The expression and activity levels of the key enzymes in the pathway, such as NAPRT and NMNAT, are critical. Age-related decline in NMNAT activity, for instance, has been linked to lower NAD+ levels.
ATP Availability: Both adenylylation and amidation steps of the Preiss-Handler pathway require ATP as a cofactor. Sufficient energy availability is therefore essential for the conversion to proceed efficiently.
Cofactors: The de novo pathway, which can converge with the Preiss-Handler pathway, is dependent on cofactors such as iron, riboflavin, and vitamin B6. While niacin conversion is more direct, overall cellular health and nutrient status can still play a role.
Inflammation: Increased inflammatory states can accelerate NAD+ degradation, placing a higher demand on all synthesis pathways.

Niacin Conversion Pathways vs. Other Precursors


Feature	Preiss-Handler Pathway (from Niacin)	Salvage Pathway (from Nicotinamide)	De Novo Pathway (from Tryptophan)
Starting Material	Niacin (Nicotinic Acid)	Nicotinamide (NAM)	Tryptophan
Number of Steps	Three	Two	Eight
Key Intermediates	NAMN, NAAD	NMN	QA, NAMN, NAAD
Rate-Limiting Enzyme	NAPRT	NAMPT	QPRT
Energy Cost	2-3 ATP molecules	2 ATP molecules	Up to 4 ATP molecules
Efficiency	Highly efficient, particularly in replenishing systemic NAD+	Highly efficient for recycling breakdown products	Inefficient; uses much more tryptophan than niacin equivalent
Tissue Location	Broadly expressed; particularly in liver and kidneys	Most mammalian tissues	Mainly liver, kidneys, and immune cells

Conclusion: Niacin's Role in a Complex Network

Niacin's conversion to NAD+ via the Preiss-Handler pathway is a fundamental and efficient process for replenishing the body's NAD+ reserves. While the body can also synthesize NAD+ from tryptophan or recycle nicotinamide, the niacin-specific pathway offers a direct route for cells, especially in certain tissues, to bolster their NAD+ supply. The efficiency of this process is influenced by enzyme availability, energy status, and overall nutritional health. Understanding the biochemistry of this conversion highlights the interconnectedness of metabolic pathways and the importance of nutritional status for maintaining cellular function and resilience against factors like aging and stress. As research into NAD+ metabolism continues, the specific roles of each precursor pathway in different tissues and life stages will become even clearer, reinforcing the importance of a balanced approach to supporting cellular health.

For more comprehensive information on the biochemical pathways of NAD+ metabolism, a detailed review is available from the National Institutes of Health (NIH).

Frequently Asked Questions

The Preiss-Handler pathway is the metabolic route used by the body to convert dietary niacin (nicotinic acid) into the coenzyme NAD+. It is a three-step enzymatic process involving the intermediate molecules NAMN and NAAD.

Niacin (nicotinic acid) and niacinamide (nicotinamide) are two forms of vitamin B3. Niacin is converted to NAD+ via the Preiss-Handler pathway, while niacinamide is recycled back into NAD+ through a different route called the salvage pathway.

Yes, the conversion of niacin to NAD+ requires energy in the form of ATP. The adenylylation step, where NAMN is converted to NAAD, and the final amidation step both consume ATP to drive the reactions forward.

Yes, the body can synthesize NAD+ from other precursors. These include the amino acid tryptophan (via the de novo pathway), nicotinamide (via the salvage pathway), and nicotinamide riboside.

NAD+ is a critical coenzyme for over 500 enzymatic reactions in the body. It is essential for energy metabolism, DNA repair, and gene expression, and declining levels are associated with aging and metabolic dysfunction.

The first step of the Preiss-Handler pathway, which involves the enzyme nicotinate phosphoribosyltransferase (NAPRT), is the rate-limiting step. Its activity can control the overall speed of the conversion process.

Yes, different tissues have varying reliance on the different NAD+ synthesis pathways. For example, while the liver is a major site for the de novo pathway, many other tissues efficiently utilize the salvage pathways, including the Preiss-Handler route from niacin.