How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant Activity
Pyridoxamine, one of the natural forms of vitamin B<sub>6</sub>, is known to be an effective inhibitor of the formation of advanced glycation end products (AGEs), which are closely related to various human diseases. Pyridoxamine forms stable complexes with metal ions that catalyze the ox...
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| Format: | Article |
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MDPI AG
2019-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/8/9/344 |
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| author | Rafael Ramis Joaquín Ortega-Castro Carmen Caballero Rodrigo Casasnovas Antonia Cerrillo Bartolomé Vilanova Miquel Adrover Juan Frau |
| author_facet | Rafael Ramis Joaquín Ortega-Castro Carmen Caballero Rodrigo Casasnovas Antonia Cerrillo Bartolomé Vilanova Miquel Adrover Juan Frau |
| author_sort | Rafael Ramis |
| collection | DOAJ |
| description | Pyridoxamine, one of the natural forms of vitamin B<sub>6</sub>, is known to be an effective inhibitor of the formation of advanced glycation end products (AGEs), which are closely related to various human diseases. Pyridoxamine forms stable complexes with metal ions that catalyze the oxidative reactions taking place in the advanced stages of the protein glycation cascade. It also reacts with reactive carbonyl compounds generated as byproducts of protein glycation, thereby preventing further protein damage. We applied Density Functional Theory to study the primary antioxidant activity of pyridoxamine towards three oxygen-centered radicals (•OOH, •OOCH<sub>3</sub> and •OCH<sub>3</sub>) to find out whether this activity may also play a crucial role in the context of protein glycation inhibition. Our results show that, at physiological pH, pyridoxamine can trap the •OCH<sub>3</sub> radical, in both aqueous and lipidic media, with rate constants in the diffusion limit (>1.0 × 10<sup>8</sup> M<inline-formula> <math display="inline"> <semantics> <msup> <mrow></mrow> <mrow> <mo>−</mo> <mn>1</mn> </mrow> </msup> </semantics> </math> </inline-formula> s<inline-formula> <math display="inline"> <semantics> <msup> <mrow></mrow> <mrow> <mo>−</mo> <mn>1</mn> </mrow> </msup> </semantics> </math> </inline-formula>). The quickest pathways involve the transfer of the hydrogen atoms from the protonated pyridine nitrogen, the protonated amino group or the phenolic group. Its reactivity towards •OOH and •OOCH<sub>3</sub> is smaller, but pyridoxamine can still scavenge them with moderate rate constants in aqueous media. Since reactive oxygen species are also involved in the formation of AGEs, these results highlight that the antioxidant capacity of pyridoxamine is also relevant to explain its inhibitory role on the glycation process. |
| first_indexed | 2024-03-12T04:41:03Z |
| format | Article |
| id | doaj.art-6f1e31400dfc49639e0f66ec7cac136c |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-12T04:41:03Z |
| publishDate | 2019-09-01 |
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| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-6f1e31400dfc49639e0f66ec7cac136c2023-09-03T09:38:58ZengMDPI AGAntioxidants2076-39212019-09-018934410.3390/antiox8090344antiox8090344How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant ActivityRafael Ramis0Joaquín Ortega-Castro1Carmen Caballero2Rodrigo Casasnovas3Antonia Cerrillo4Bartolomé Vilanova5Miquel Adrover6Juan Frau7Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainInstitut Universitari d’Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainInstitut Universitari d’Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainInstitut Universitari d’Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainInstitut Universitari d’Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainInstitut Universitari d’Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainInstitut Universitari d’Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainInstitut Universitari d’Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainPyridoxamine, one of the natural forms of vitamin B<sub>6</sub>, is known to be an effective inhibitor of the formation of advanced glycation end products (AGEs), which are closely related to various human diseases. Pyridoxamine forms stable complexes with metal ions that catalyze the oxidative reactions taking place in the advanced stages of the protein glycation cascade. It also reacts with reactive carbonyl compounds generated as byproducts of protein glycation, thereby preventing further protein damage. We applied Density Functional Theory to study the primary antioxidant activity of pyridoxamine towards three oxygen-centered radicals (•OOH, •OOCH<sub>3</sub> and •OCH<sub>3</sub>) to find out whether this activity may also play a crucial role in the context of protein glycation inhibition. Our results show that, at physiological pH, pyridoxamine can trap the •OCH<sub>3</sub> radical, in both aqueous and lipidic media, with rate constants in the diffusion limit (>1.0 × 10<sup>8</sup> M<inline-formula> <math display="inline"> <semantics> <msup> <mrow></mrow> <mrow> <mo>−</mo> <mn>1</mn> </mrow> </msup> </semantics> </math> </inline-formula> s<inline-formula> <math display="inline"> <semantics> <msup> <mrow></mrow> <mrow> <mo>−</mo> <mn>1</mn> </mrow> </msup> </semantics> </math> </inline-formula>). The quickest pathways involve the transfer of the hydrogen atoms from the protonated pyridine nitrogen, the protonated amino group or the phenolic group. Its reactivity towards •OOH and •OOCH<sub>3</sub> is smaller, but pyridoxamine can still scavenge them with moderate rate constants in aqueous media. Since reactive oxygen species are also involved in the formation of AGEs, these results highlight that the antioxidant capacity of pyridoxamine is also relevant to explain its inhibitory role on the glycation process.https://www.mdpi.com/2076-3921/8/9/344pyridoxamineDFTAGEsinhibitionROS |
| spellingShingle | Rafael Ramis Joaquín Ortega-Castro Carmen Caballero Rodrigo Casasnovas Antonia Cerrillo Bartolomé Vilanova Miquel Adrover Juan Frau How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant Activity Antioxidants pyridoxamine DFT AGEs inhibition ROS |
| title | How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant Activity |
| title_full | How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant Activity |
| title_fullStr | How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant Activity |
| title_full_unstemmed | How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant Activity |
| title_short | How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant Activity |
| title_sort | how does pyridoxamine inhibit the formation of advanced glycation end products the role of its primary antioxidant activity |
| topic | pyridoxamine DFT AGEs inhibition ROS |
| url | https://www.mdpi.com/2076-3921/8/9/344 |
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