ArticleNature communications2023
Network-wide thermodynamic constraints shape NAD(P)H cofactor specificity of biochemical reactions.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Thermodynamic metabolic modeling of growth and bioproduction potential of the acetogenSynthetic and systems biotechnology · 2026Article
- A sequence motif enables widespread use of noncanonical redox cofactors in natural enzymes.Nature chemical biology · 2026Article
- Defining Rational Photoelectron Routing for Targeted Intracellular Energy Transfer.Angewandte Chemie (International ed. in English) · 2026Article
- COBRA-k: A powerful framework bridging constraint-based and kinetic metabolic modeling.Science advances · 2026Article
- Mechanism of cyanobacterial ferredoxin-dependent flavin thioredoxin reductase reveals thiolate-FAD charge transfer and catalytic asymmetry in a homodimer.The FEBS journal · 2026Article
- Network-wide thermodynamic constraints shape NAD(P)H cofactor specificity of biochemical reactions.Nature communications · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
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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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