Lysine β-Hydroxybutyrylation Improves Stability of COVID-19 Antibody

Li, Zihua; Zhang, Yudian; Han, Meng; Deng, Haiteng; Wu, Fuqing; Liu, Gang; Chen, Guo‐Qiang

doi:10.1021/acs.biomac.1c01435

Cited by 10 publications

(8 citation statements)

References 44 publications

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“…In contrast, the COVID-19 cases in our study were not considered to be severe. The health benefits of beta-hydroxybutyric acid have prompted researchers to advocate for metabolic therapies that raise beta-hydroxybutyric acid levels to treat severe COVID-19 37 , 38 ; as beta-hydroxybutyric acid was found to reduce coronavirus-dependent inflammation in mice 39 and, protect COVID-19 antibodies against degradation through a post-translational modification 40 . To address the discordance between the therapeutic potential of beta-hydroxybutyric acid and its association with worsening COVID-19 disease, we speculate that in the acute phase of COVID-19, the liver synthesizes beta-hydroxybutyric acid, in part, to replenish depleted energy stores; however, as the patient deteriorates, liver function becomes impaired 36 , resulting in dysregulated overproduction of beta-hydroxybutyric acid and other ketone bodies.…”

Section: Discussionmentioning

confidence: 99%

Small-molecule metabolome identifies potential therapeutic targets against COVID-19

Bennet

Kaufmann

Takami

et al. 2022

Sci Rep

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Respiratory viruses are transmitted and acquired via the nasal mucosa, and thereby may influence the nasal metabolome composed of biochemical products produced by both host cells and microbes. Studies of the nasal metabolome demonstrate virus-specific changes that sometimes correlate with viral load and disease severity. Here, we evaluate the nasopharyngeal metabolome of COVID-19 infected individuals and report several small molecules that may be used as potential therapeutic targets. Specimens were tested by qRT-PCR with target primers for three viruses: Influenza A (INFA), respiratory syncytial virus (RSV), and SARS-CoV-2, along with unaffected controls. The nasopharyngeal metabolome was characterized using an LC–MS/MS-based screening kit capable of quantifying 141 analytes. A machine learning model identified 28 discriminating analytes and correctly categorized patients with a viral infection with an accuracy of 96% (R2 = 0.771, Q2 = 0.72). A second model identified 5 analytes to differentiate COVID19-infected patients from those with INFA or RSV with an accuracy of 85% (R2 = 0.442, Q2 = 0.301). Specifically, Lysophosphatidylcholines-a-C18:2 (LysoPCaC18:2) concentration was significantly increased in COVID19 patients (P < 0.0001), whereas beta-hydroxybutyric acid, Methionine sulfoxide, succinic acid, and carnosine concentrations were significantly decreased (P < 0.0001). This study demonstrates that COVID19 infection results in a unique nasopharyngeal metabolomic signature with carnosine and LysoPCaC18:2 as potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Small-molecule metabolome identifies potential therapeutic targets against COVID-19

Bennet

Kaufmann

Takami

et al. 2022

Sci Rep

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“…3HB is assumed to exert its functions via the post-translational modifications (PTMs), namely, “β-hydroxybutyrylation” on histone and non-histone proteins [ 76 – 80 ], “sense” metabolic changes caused by the disused and modulated downstream gene expression. Although 3HB is an important fuel molecule with high energetic efficiency, the current approach is not precise enough to observe the reallocation of energy substrates in terms of glycolysis (Additional file 1 : Fig.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of reduced muscle atrophy via ketone body (D)-3-hydroxybutyrate

Chen

Zhang

et al. 2022

Cell Biosci

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Background Muscle atrophy is an increasingly global health problem affecting millions, there is a lack of clinical drugs or effective therapy. Excessive loss of muscle mass is the typical characteristic of muscle atrophy, manifesting as muscle weakness accompanied by impaired metabolism of protein and nucleotide. (D)-3-hydroxybutyrate (3HB), one of the main components of the ketone body, has been reported to be effective for the obvious hemodynamic effects in atrophic cardiomyocytes and exerts beneficial metabolic reprogramming effects in healthy muscle. This study aims to exploit how the 3HB exerts therapeutic effects for treating muscle atrophy induced by hindlimb unloaded mice. Results Anabolism/catabolism balance of muscle protein was maintained with 3HB via the Akt/FoxO3a and the mTOR/4E-BP1 pathways; protein homeostasis of 3HB regulation includes pathways of ubiquitin–proteasomal, autophagic-lysosomal, responses of unfolded-proteins, heat shock and anti-oxidation. Metabolomic analysis revealed the effect of 3HB decreased purine degradation and reduced the uric acid in atrophied muscles; enhanced utilization from glutamine to glutamate also provides evidence for the promotion of 3HB during the synthesis of proteins and nucleotides. Conclusions 3HB significantly inhibits the loss of muscle weights, myofiber sizes and myofiber diameters in hindlimb unloaded mouse model; it facilitates positive balance of proteins and nucleotides with enhanced accumulation of glutamate and decreased uric acid in wasting muscles, revealing effectiveness for treating muscle atrophy. Graphical Abstract

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“… 479 β‐Hydroxybutyrate forms covalent bonds with lysine side chains in proteins during ketogenesis, leading to Kbhb. 536 , 540 Kbhb is a sensitive indicator of changes in energy metabolism. Under starvation conditions, histone Kbhb levels in the mouse liver are significantly elevated, which can impact metabolic pathways such as amino acid catabolism.…”

Section: Other Scfa Modificationsmentioning

confidence: 99%

“…Hypoglycemia leads to ketogenesis, producing β‐hydroxybutyrate 479 . β‐Hydroxybutyrate forms covalent bonds with lysine side chains in proteins during ketogenesis, leading to Kbhb 536,540 . Kbhb is a sensitive indicator of changes in energy metabolism.…”

Section: Other Scfa Modificationsmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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Lysine β-Hydroxybutyrylation Improves Stability of COVID-19 Antibody

Cited by 10 publications

References 44 publications

Small-molecule metabolome identifies potential therapeutic targets against COVID-19

Small-molecule metabolome identifies potential therapeutic targets against COVID-19

Mechanism of reduced muscle atrophy via ketone body (D)-3-hydroxybutyrate

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

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