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Nicotinate metabolism
Summary
- Organism
- Homo sapiens (human)
- Reactome
- R-HSA-196807
- PubChem
- R-HSA-196807
- Description
-
- Nicotinate (niacin) and nicotinamide are precursors of the coenzymes nicotinamide-adenine dinucleotide (NAD+) and nicotinamide-adenine dinucleotide phosphate (NADP+), essential cofactors in many redox reactions. The cytosolic reactions that generate NAD+ can be classified into three groups (Cambronne & Krause 2020; Covarrubias et al. 2021; Magni et al. 2004). First, in the de novo or kynurenine pathway, ACS derived from tryptophan catabolism is spontaneously converted to QUIN, which in turn is converted successively to NAMN, NAAD, and NAD+ in reactions catalyzed by QPRT, NMNAT2, and NADSYN1. These are the first four reactions listed here. Second, in the Preiss–Handler pathway, the next three reactions listed here, extracellular nicotinate (NCA), transported into the cytosol by SLC22A13 or SLC5A3, is converted to nicotinate D-ribonucleotide (NAMN), which can enter the de novo pathway to be converted to NAD+.
The remaining large group of reactions enables the modulation of nicotinamide (NAM) levels and the regeneration of NAD+ from diverse metabolic intermediates. Enzymes that play central roles in these processes include nicotinamide phosphoribosyltransferase (NAMPT), and nicotinate phosphoribosyltransferase (NAPRT1). These enzymes are poorly characterized in humans, despite their importance in NAM utilization (Magni et al. 2004). NAM levels are also regulated by nicotinamide N-methyltransferase (NNMT), a potential regulator of diet-induced obesity (Kraus et al. 2014).
Reactions mediating parts of these processes but localized to the nucleus, mitochondria, and peroxisomes are also included in this pathway.
- Nicotinate (niacin) and nicotinamide are precursors of the coenzymes nicotinamide-adenine dinucleotide (NAD+) and nicotinamide-adenine dinucleotide phosphate (NADP+), essential cofactors in many redox reactions. The cytosolic reactions that generate NAD+ can be classified into three groups (Cambronne & Krause 2020; Covarrubias et al. 2021; Magni et al. 2004). First, in the de novo or kynurenine pathway, ACS derived from tryptophan catabolism is spontaneously converted to QUIN, which in turn is converted successively to NAMN, NAAD, and NAD+ in reactions catalyzed by QPRT, NMNAT2, and NADSYN1. These are the first four reactions listed here. Second, in the Preiss–Handler pathway, the next three reactions listed here, extracellular nicotinate (NCA), transported into the cytosol by SLC22A13 or SLC5A3, is converted to nicotinate D-ribonucleotide (NAMN), which can enter the de novo pathway to be converted to NAD+.
Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.
| UniProt ID | Protein Name | Gene Symbol | Pathway Viewer |
|---|---|---|---|
| P21589 | 5'-nucleotidase |
|
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| P28907 | ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 |
|
view |
| Q10588 | ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 |
|
view |
| Q460N5 | Protein mono-ADP-ribosyltransferase PARP14 |
|
view |
| Q53GL7 | Protein mono-ADP-ribosyltransferase PARP10 |
|
view |
| Q6IA69 | Glutamine-dependent NAD(+) synthetase |
|
view |
| Q8IW45 | ATP-dependent (S)-NAD(P)H-hydrate dehydratase |
|
view |
| Q8N695 | Sodium-coupled monocarboxylate transporter 1 |
|
view |
| Q8NCW5 | NAD(P)H-hydrate epimerase |
|
view |
| Q9UKK3 | Protein mono-ADP-ribosyltransferase PARP4 |
|
view |
