The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions
Cellular metabolism assembles in a structurally highly conserved, but functionally dynamic system, known as the metabolic network. This network involves highly active, enzyme-catalyzed metabolic pathways that provide the building blocks for cell growth. In parallel, however, chemical reactivity of m...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-09-01
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| Series: | Biomolecules |
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| Online Access: | http://www.mdpi.com/2218-273X/5/3/2101 |
| _version_ | 1818328292878450688 |
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| author | Gabriel Piedrafita Markus A Keller Markus Ralser |
| author_facet | Gabriel Piedrafita Markus A Keller Markus Ralser |
| author_sort | Gabriel Piedrafita |
| collection | DOAJ |
| description | Cellular metabolism assembles in a structurally highly conserved, but functionally dynamic system, known as the metabolic network. This network involves highly active, enzyme-catalyzed metabolic pathways that provide the building blocks for cell growth. In parallel, however, chemical reactivity of metabolites and unspecific enzyme function give rise to a number of side products that are not part of canonical metabolic pathways. It is increasingly acknowledged that these molecules are important for the evolution of metabolism, affect metabolic efficiency, and that they play a potential role in human disease—age-related disorders and cancer in particular. In this review we discuss the impact of oxidative and other cellular stressors on the formation of metabolic side products, which originate as a consequence of: (i) chemical reactivity or modification of regular metabolites; (ii) through modifications in substrate specificity of damaged enzymes; and (iii) through altered metabolic flux that protects cells in stress conditions. In particular, oxidative and heat stress conditions are causative of metabolite and enzymatic damage and thus promote the non-canonical metabolic activity of the cells through an increased repertoire of side products. On the basis of selected examples, we discuss the consequences of non-canonical metabolic reactivity on evolution, function and repair of the metabolic network. |
| first_indexed | 2024-12-13T12:29:51Z |
| format | Article |
| id | doaj.art-f27c0b57c28445ca9915964a869b87b3 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-13T12:29:51Z |
| publishDate | 2015-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-f27c0b57c28445ca9915964a869b87b32022-12-21T23:46:05ZengMDPI AGBiomolecules2218-273X2015-09-01532101212210.3390/biom5032101biom5032101The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress ConditionsGabriel Piedrafita0Markus A Keller1Markus Ralser2Department of Biochemistry, University of Cambridge, 80 Tennis Court Rd, Cambridge CB2 1GA, UKDepartment of Biochemistry, University of Cambridge, 80 Tennis Court Rd, Cambridge CB2 1GA, UKDepartment of Biochemistry, University of Cambridge, 80 Tennis Court Rd, Cambridge CB2 1GA, UKCellular metabolism assembles in a structurally highly conserved, but functionally dynamic system, known as the metabolic network. This network involves highly active, enzyme-catalyzed metabolic pathways that provide the building blocks for cell growth. In parallel, however, chemical reactivity of metabolites and unspecific enzyme function give rise to a number of side products that are not part of canonical metabolic pathways. It is increasingly acknowledged that these molecules are important for the evolution of metabolism, affect metabolic efficiency, and that they play a potential role in human disease—age-related disorders and cancer in particular. In this review we discuss the impact of oxidative and other cellular stressors on the formation of metabolic side products, which originate as a consequence of: (i) chemical reactivity or modification of regular metabolites; (ii) through modifications in substrate specificity of damaged enzymes; and (iii) through altered metabolic flux that protects cells in stress conditions. In particular, oxidative and heat stress conditions are causative of metabolite and enzymatic damage and thus promote the non-canonical metabolic activity of the cells through an increased repertoire of side products. On the basis of selected examples, we discuss the consequences of non-canonical metabolic reactivity on evolution, function and repair of the metabolic network.http://www.mdpi.com/2218-273X/5/3/2101oxidative stressreactive oxygen speciesmetabolic damagemetabolite repairenzyme promiscuityunderground metabolism |
| spellingShingle | Gabriel Piedrafita Markus A Keller Markus Ralser The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions Biomolecules oxidative stress reactive oxygen species metabolic damage metabolite repair enzyme promiscuity underground metabolism |
| title | The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions |
| title_full | The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions |
| title_fullStr | The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions |
| title_full_unstemmed | The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions |
| title_short | The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions |
| title_sort | impact of non enzymatic reactions and enzyme promiscuity on cellular metabolism during oxidative stress conditions |
| topic | oxidative stress reactive oxygen species metabolic damage metabolite repair enzyme promiscuity underground metabolism |
| url | http://www.mdpi.com/2218-273X/5/3/2101 |
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