Murburn posttranslational modifications of proteins: Cellular redox processes and murzyme‐mediated metabolo‐proteomics

Abstract

Murburn concept constitutes the thesis that diffusible reactive species or DRS are obligatorily involved in routine metabolic and physiological activities. Murzymes are defined as biomolecules/proteins that generate/modulate/sustain/utilize DRS. Murburn posttranslational modifications (PTMs) result because murburn/murzyme functionalism is integral to cellular existence. Cells must incorporate the inherently stochastic nature of operations mediated by DRS. Due to the earlier/inertial stigmatic perception that DRS are mere agents of chaos, several such outcomes were either understood as deterministic modulations sponsored by house‐keeping enzymes or deemed as unregulated nonenzymatic events resulting out of “oxidative stress”. In the current review, I dispel the myths around DRS‐functions, and undertake systematic parsing and analyses of murburn modifications of proteins. Although it is impossible to demarcate all PTMs into the classical or murburn modalities, telltale signs of the latter are evident from the relative inaccessibility of the locus, non‐specificities and mechanistic details. It is pointed out that while many murburn PTMs may be harmless, some others could have deleterious or beneficial physiological implications. Some details of reversible/irreversible modifications of amino acid residues and cofactors that may be subjected to phosphorylation, halogenation, glycosylation, alkylation/acetylation, hydroxylation/oxidation, etc. are listed, along with citations of select proteins where such modifications have been reported. The contexts of these modifications and their significance in (patho)physiology/aging and therapy are also presented. With more balanced explorations and statistically verified data, a definitive understanding of normal versus pathological contexts of murburn modifications would be obtainable in the future.

Murburn concept in cellular function and bioenergetics, Part 1: Understanding murzymes at the molecular level

“…Thus, the stochastic murburn concept supplements the deterministic central dogma for explaining the holistic metabolic and bioenergetic functioning of cells. Figure 2 shows a scheme for understanding murburn concept at molecular, systemic and conceptual levels (42,57,60).…”

What Is the Relevance of Murburn Concept in Thalassemia and Respiratory Diseases?

“…This role of Hb makes up for the inadeq colytic ATP-synthesis in RBC and explains the hetero-tetrameric struct pore on the beta globin monomer [25]. In this connection, it must also DR(O)S production ability of Hb enables it to catalyze several auto-and lational modifications such as glycations, phosphorylations, etc., which markers in clinical research [42]. Murburn concept postulates that DRS produced in oxygen-water equilibriums are not to be seen purely as "oxidative stress" agents (dangerous and toxic waste products), but they serve as obligatorily required intermediates essential for cellular powering, coherence, homeostasis, electromechanics, etc.…”

“…This role of Hb makes up for the inadequate output of glycolytic ATP-synthesis in RBC and explains the hetero-tetrameric structure of Hb, with the pore on the beta globin monomer [25]. In this connection, it must also be noted that the DR(O)S production ability of Hb enables it to catalyze several auto-and hetero-post translational modifications such as glycations, phosphorylations, etc., which are also important markers in clinical research [42].…”

Protein modifications and diseases

“…Murburn modification of proteins bases on diffusible reactive species (DRS) generation and utilization, and DRS are obligatorily involved in fundamental metabolic and physiological activities (Manoj, 2023). In this review, Manoj (2023) investigated DRS‐functions, undertake systematic parsing and analyses on protein substrates of murburn modifications. Moreover, Liu et al (2023) utilized a periodontal ligament‐associated protein‐1 (PLAP‐1/Asporin) gene KO mouse model to investigate how PLAP‐1/Asporin regulates osteoclasts and osteoblasts in periodontitis.…”

“…Lastly, this special issue includes other interesting original and review articles about epigenetic regulation and disease, including a review about murburn posttranslational modifications of proteins (Manoj, 2023). Murburn modification of proteins bases on diffusible reactive species (DRS) generation and utilization, and DRS are obligatorily involved in fundamental metabolic and physiological activities (Manoj, 2023). In this review, Manoj (2023) investigated DRS‐functions, undertake systematic parsing and analyses on protein substrates of murburn modifications.…”