Abstract
Enzymes shape cellular metabolism, are regulated, fast, and for most cases specific. Enzymes do not however prevent the parallel occurrence of non-enzymatic reactions. Non-enzymatic reactions were important for the evolution of metabolic pathways, but are retained as part of the modern metabolic network. They divide into unspecific chemical reactivity and specific reactions that occur either exclusively non-enzymatically as part of the metabolic network, or in parallel to existing enzyme functions. Non-enzymatic reactions resemble catalytic mechanisms as found in all major enzyme classes and occur spontaneously, small molecule (e.g. metal-) catalyzed or light-induced. The frequent occurrence of non-enzymatic reactions impacts on stability and metabolic network structure, and has thus to be considered in the context of metabolic disease, network modeling, biotechnology and drug design.
Highlights
The metabolic network originates from a low number of ancestral forms, and all living organisms share core reaction sequences and structural properties in their metabolic networks [1]
Three classes of non-enzymatic reactions contribute to modern cellular metabolism It is important to emphasize that the same thermodynamic principles apply for non-enzymatic and enzymatic reactions, and every enzymatic reaction can occur in principle non-enzymatically [10]
Providing a template for the evolutionary selection of metabolic enzymes, non-enzymatic reactions did form the basis for the evolution of metabolism
Summary
The metabolic network originates from a low number (or one) of ancestral forms, and all living organisms share core reaction sequences and structural properties in their metabolic networks [1]. On the basis of their principal mode of action, we divide nonenzymatic reactions into three classes (Figure 1b): Class I reactions present broad chemical reactivity and low specificity These include Maillard-reactions, a conjugation of amino group-containing compounds (e.g. amino acids) and sugars [11], oxidation reactions driven by reactive oxygen species (ROS) and non-enzymatic covalent modifications of lipids and proteins (alkylation, glycosylation and acetylation) [12]. The presence of 6PGL accelerates flux, but predominantly prevents the formation of undesired side-products produced when 6-phosphogluconolactone reacts with amino acids, lipids, polyamines or alcohols [28] Other lactonases such as aldonolactonase (L-ascorbate biosynthesis) [29] and hydrolase-type reactions such as acyl phosphatases [28], epoxide hydrolases [30] and lipoxygenase (colneleic acid degradation) [31] possess analogous non-enzymatic reactions.
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