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Review
. 2016 Nov 15;8(11):339.
doi: 10.3390/toxins8110339.

N-methyl-2-pyridone-5-carboxamide (2PY)-Major Metabolite of Nicotinamide: An Update on an Old Uremic Toxin

Aurélie Lenglet  1   2 , Sophie Liabeuf  3   4 , Sandra Bodeau  5   6 , Loïc Louvet  7 , Aurélien Mary  8   9 , Agnès Boullier  10   11 , Anne Sophie Lemaire-Hurtel  12 , Alexia Jonet  13 , Pascal Sonnet  14 , Said Kamel  15   16 , Ziad A Massy  17   18
Affiliations
Review

N-methyl-2-pyridone-5-carboxamide (2PY)-Major Metabolite of Nicotinamide: An Update on an Old Uremic Toxin

Aurélie Lenglet et al. Toxins (Basel). .

Abstract

N-methyl-2-pyridone-5-carboxamide (2PY, a major metabolite of nicotinamide, NAM) was recently identified as a uremic toxin. Recent interventional trials using NAM to treat high levels of phosphorus in end-stage renal disease have highlighted new potential uremic toxicities of 2PY. In the context of uremia, the accumulation of 2PY could be harmful-perhaps by inhibiting poly (ADP-ribose) polymerase-1 activity. Here, we review recently published data on 2PY's metabolism and toxicological profile.

Keywords: N-methyl-2-pyridone-5-carboxamide; chronic kidney disease; niacin; nicotinamide; uremic toxin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The metabolic production of N-methyl-2-pyridone-5-carboxamide.
Figure 2
Figure 2
The 2PY concentration as a function of the chronic kidney disease (CKD) stage. To get the results in µmol/L, divide by the molecular weight (152.15 Da) **** p < 0.0001.
Figure 3
Figure 3
Comparison of 2PY concentrations in chronic kidney disease (CKD) patients stage 5D at baseline and after 24 weeks of oral supplementation with nicotinamide (NAM). To get the results in µmol/L, divide by the molecular weight (152.15 Da) **** p < 0.0001 (adapted from the NICOREN study [7]).
Figure 4
Figure 4
Effects of N-methyl-2-pyridone-5-carboxamide (2PY), nicotinamide (NAM) and 3-aminobenzamide (3AB) on the activity of purified poly (ADP-ribose) polymerase-1. Data are quoted as the mean ± SD (n = 6).
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