Metabolites Modify Proteins

Metabolism is the most basic characteristic of life activities. On the one hand, metabolism can directly meet the material needs of individual growth and development through the synthesis of energy and biomacromolecules. On the other hand, more and more studies have shown that metabolites accumulated during metabolism, such as lactic acid, succinic acid, coenzyme A, amino acid and other substances, can make protein translational modifications (PTMs) to regulate growth-related signaling pathways and influence the growth and development process.

Although most metabolites bind amino acids to form PTMs by specific enzymes, in special cases, some metabolites can modify proteins through non-enzymatic reactions. For example, the acetyl groups of acetyl-CoA usually require lysineacetyl transferases (KATs), such as GNATs, MYST, or P300 /CBP, To form lysine acetylation (Kac).However, it is worth noting that although no KATs has been detected in mitochondria, mitochondrial proteins can still produce Kac. This may be because lysine is prone to nucleophilic addition reactions (non-enzymatic reactions) with acetyl-Coa thioesterbond in acidic mitochondrial environment. In contrast to the modification process, metabolite-modified proteins must depend on enzyme function, with HDACs and SIRT responsible for deacetylation. In fact, both acetyltransferases and deacetylases can regulate PTMs except for acetylation modification. KATs, P300, is also responsible for lysine lactation (Kla) and lysine crotonylation (Kcr). SIRT has also been reported to play a role in the modification of succinylation and malonylation.

In recent years, thanks to high precision mass spectrometry, many remarkable achievements have been made in the field of proteomic modification, especially the revelation of the role of various metabolites in protein modification, which to a large extent reshaped people’s understanding of the complexity of biological microscopic regulation.

References：

[1] Di Zhang, et al., 2019. Metabolic regulation of gene expression by histone lactylation.Nature.

[2]  Ziqiang Wang, et al.,2019. NEAT1 regulates neuroglial cell mediating Aβ clearance via the epigenetic regulation of endocytosis related genes expression.Cellular and Molecular Life Sciences.

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