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Abstract <p><i>S</i>-adenosyl-<i>L</i>-methionine (SAM, AdoMet) is a ubiquitous biomolecule present in all living organisms, playing a central role in a wide array of biochemical reactions and intracellular regulatory pathways. It is the second most common participant in enzymatic reactions in living systems, following adenosine triphosphate (ATP). This review provides a comprehensive analysis of enzymatic reactions involving SAM, whether as a product, a reactant (cosubstrate), or as a non-consumable enzyme cofactor. The discussion encompasses various methods for SAM synthesis, including biotechnological, chemical, and enzymatic approaches. Particular emphasis is placed on the biochemical reactions where SAM functions as a cosubstrate, notably in trans-alkylation reactions, where it acts as a key methyl group donor. Beyond methylation, SAM also serves as a precursor for the synthesis of other molecular building blocks, which are explored in a dedicated section. The review also addresses the role of SAM as a non-consumable cofactor in enzymatic processes, highlighting its function as a prosthetic group for certain protein enzymes and its ability to form complexes with ribozymes. In addition, bioorthogonal systems involving SAM analogues are discussed. These systems employ engineered enzyme–cofactor pairs designed to enable highly selective interactions between target SAM analogues and specific enzymes, facilitating precise reactions even in the presence of other SAM-dependent enzymes. The concluding section explores practical applications of SAM analogues, including their use as selective inhibitors in clinical medicine and as components of reporter systems.</p>

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Enzymatic Reactions of S-Adenosyl-L-Methionine: Synthesis and Applications

  • 期刊论文

  • 发表日期：

    2025年2月1日

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  • Alexander Yu. Rudenko,
  • Sofia S. Mariasina,
  • Ratislav M. Ozhiganov,
  • Petr V. Sergiev,
  • Vladimir I. Polshakov

摘要

Abstract

S-adenosyl-L-methionine (SAM, AdoMet) is a ubiquitous biomolecule present in all living organisms, playing a central role in a wide array of biochemical reactions and intracellular regulatory pathways. It is the second most common participant in enzymatic reactions in living systems, following adenosine triphosphate (ATP). This review provides a comprehensive analysis of enzymatic reactions involving SAM, whether as a product, a reactant (cosubstrate), or as a non-consumable enzyme cofactor. The discussion encompasses various methods for SAM synthesis, including biotechnological, chemical, and enzymatic approaches. Particular emphasis is placed on the biochemical reactions where SAM functions as a cosubstrate, notably in trans-alkylation reactions, where it acts as a key methyl group donor. Beyond methylation, SAM also serves as a precursor for the synthesis of other molecular building blocks, which are explored in a dedicated section. The review also addresses the role of SAM as a non-consumable cofactor in enzymatic processes, highlighting its function as a prosthetic group for certain protein enzymes and its ability to form complexes with ribozymes. In addition, bioorthogonal systems involving SAM analogues are discussed. These systems employ engineered enzyme–cofactor pairs designed to enable highly selective interactions between target SAM analogues and specific enzymes, facilitating precise reactions even in the presence of other SAM-dependent enzymes. The concluding section explores practical applications of SAM analogues, including their use as selective inhibitors in clinical medicine and as components of reporter systems.