The Role of Branched-Chain Amino Acids and Branched-Chain α-Keto Acid Dehydrogenase Kinase in Metabolic Disorders

Du, Chao‐Hai; Liu, Wenjie; Yang, Jing; Zhao, Shuang; Liu, Hui‐Xin

doi:10.3389/fnut.2022.932670

Cited by 40 publications

(26 citation statements)

References 81 publications

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“…Our data also demonstrated the alterations in the metabolism of branched-chain amino acids (BCAAs). BCAAs include valine, leucine, and isoleucine which are essential for organisms 42, 43 . It has been shown that BCAAs activate T cell types via mTOR signaling and glucose metabolism 44, 45, 46 .…”

Section: Resultsmentioning

confidence: 99%

Low albumin status accompanies multi-layered immunosuppressive phenotypes in metastatic breast cancer patients

Nakamura,

Yoda,

Izumi

et al. 2023

Preprint

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Low albumin status is prevalent in advanced cancer patients, but the pathophysiology associated with this anomaly remains largely unexplored. To address this, we aim to search correlations of albumin levels with the transcriptome against peripheral blood mononuclear cells and the plasma metabolome within the same patients having metastatic breast cancers. We confirm that metastatic breast cancer patients exhibit low albumin levels in varying degrees without prominent systemic inflammation. Our data demonstrate that low albumin levels correlate with transcriptome signatures indicative of neutrophil activation and T-cell down-regulation, an immunosuppressive phenotype. We also find that immunoregulatory metabolites, such as arginine, are reduced in plasma in an albumin-correlated manner, further corroborating systemic immunosuppression. These results are verified using a mouse model of breast cancer. We conclude that low albumin status in metastatic breast cancer patients accompanies immunosuppressive phenotypes, which is likely unfavorable for anti-cancer immunotherapy and thus can be a cause of unsuccessful treatment outcomes.

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Section: Resultsmentioning

confidence: 99%

Low albumin status accompanies multi-layered immunosuppressive phenotypes in metastatic breast cancer patients

Nakamura,

Yoda,

Izumi

et al. 2023

Preprint

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“…Branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are all essential AAs that can only be synthesized by bacteria, plants, and fungi, and also can be acquired from dietary chicken breast, beef, tuna, beans, and cherries. In contrast to the majority of AAs, BCAAs are converted to their branched-chain α-keto acids (BCKAs) in skeletal muscle and then released into systemic circulation [ 72 ]. BCAAs are well known for their crucial role in promotion of muscle-protein synthesis and modulation of energy metabolism during exercise, which are both mediated through activation of the mTOR signaling pathway [ 73 ].…”

Section: Branched-chain Amino Acidsmentioning

confidence: 99%

Metabolic Homeostasis of Amino Acids and Diabetic Kidney Disease

Luo-kun

Zhang

et al. 2022

Nutrients

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Diabetic kidney disease (DKD) occurs in 25–40% of patients with diabetes. Individuals with DKD are at a significant risk of progression to end-stage kidney disease morbidity and mortality. At present, although renal function-decline can be retarded by intensive glucose lowering and strict blood pressure control, these current treatments have shown no beneficial impact on preventing progression to kidney failure. Recently, in addition to control of blood sugar and pressure, a dietary approach has been recommended for management of DKD. Amino acids (AAs) are both biomarkers and causal factors of DKD progression. AA homeostasis contributes to renal hemodynamic response and glomerular hyperfiltration alteration in diabetic patients. This review discusses the links between progressive kidney dysfunction and the metabolic homeostasis of histidine, tryptophan, methionine, glutamine, tyrosine, and branched-chain AAs. In addition, we emphasize the regulation effects of special metabolites on DKD progression, with a focus on causality and potential mechanisms. This paper may offer an optimized protein diet strategy with concomitant management of AA homeostasis to reduce the risks of DKD in a setting of hyperglycemia.

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“…Consistent with protein-host interactions whose consequences lie in mitochondrial dysfunctions, the SARS-CoV-2 nsp12 protein has been suggested to inhibit branched-chain keto acid dehydrogenase kinase (BCKDK), a branched-chain amino acid kinase regulatory enzyme [26,43]. Interestingly, the accumulation of branchedchain amino acids, which in turn can inhibit pyruvate dehydrogenase, mitochondrial respiration chain and α-ketoglutarate dehydrogenase, can cause apoptosis in glial cells and neurons [44]. In addition, the nsp7 and nsp8 proteins have been described as two cofactors of the nsp12 protein, and both interact with ribosomal proteins in mitochondria [43].…”

Section: Cytopathic Effects On Mitochondriamentioning

confidence: 99%

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

Gonzalez-Garcia¹,

Moreno²,

Peñate³

et al. 2023

Preprint

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Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and Long-COVID.

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The Role of Branched-Chain Amino Acids and Branched-Chain α-Keto Acid Dehydrogenase Kinase in Metabolic Disorders

Cited by 40 publications

References 81 publications

Low albumin status accompanies multi-layered immunosuppressive phenotypes in metastatic breast cancer patients

Low albumin status accompanies multi-layered immunosuppressive phenotypes in metastatic breast cancer patients

Metabolic Homeostasis of Amino Acids and Diabetic Kidney Disease

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

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