AI Article Synopsis
- The study explores how the presence of redox cofactors NADH and NADPH influences cellular redox metabolism and investigates the factors determining their specificities in metabolic reactions.
- A computational framework is used to assess the impact of swapping redox cofactors on the efficiency of metabolic networks, particularly in Escherichia coli, revealing insights into the structural and thermodynamic factors that shape NAD(P)H specificity.
- Results indicate that while redundancy in NAD(P)H enhances thermodynamic efficiency in metabolic processes, introducing a third cofactor would only be beneficial if it has a low standard redox potential; predictions about redox cofactor concentration ratios are also provided to aid in designing optimal specificities.
Article Abstract
The ubiquitous coexistence of the redox cofactors NADH and NADPH is widely considered to facilitate an efficient operation of cellular redox metabolism. However, it remains unclear what shapes the NAD(P)H specificity of specific redox reactions. Here, we present a computational framework to analyze the effect of redox cofactor swaps on the maximal thermodynamic potential of a metabolic network and use it to investigate key aspects of redox cofactor redundancy in Escherichia coli. As one major result, our analysis suggests that evolved NAD(P)H specificities are largely shaped by metabolic network structure and associated thermodynamic constraints enabling thermodynamic driving forces that are close or even identical to the theoretical optimum and significantly higher compared to random specificities. Furthermore, while redundancy of NAD(P)H is clearly beneficial for thermodynamic driving forces, a third redox cofactor would require a low standard redox potential to be advantageous. Our approach also predicts trends of redox-cofactor concentration ratios and could facilitate the design of optimal redox cofactor specificities.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400544 | PMC |
| http://dx.doi.org/10.1038/s41467-023-40297-8 | DOI Listing |
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