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Metabolites
Special Issues
Amino Acid Metabolism in Health and Disease
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Amino Acid Metabolism in Health and Disease

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (1 March 2022) | Viewed by 20605

Special Issue Editor

Dr. Silvia Sacchi

E-Mail Website
Guest Editor
Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy
Interests: D-amino acids metabolism; flavooxidases; neurochemistry; protein-protein interaction; protein function regulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Amino acids are not only the building blocks of proteins; they also act as intermediate metabolites fueling different biosynthetic pathways, and some function as or are synthesized into important molecules such as neurotransmitters, hormones, pigments, and oxygen-carrying molecules. Thus, plasma and intracellular amino acid availability and homeostasis are crucial and require a coordinated metabolism of synthetic, catabolic, and transport pathways. Accordingly, amino acid-related metabolic disorders comprise a very heterogeneous group of diseases, whose severity may range from mild to highly disabling illness, brain damage, or multi-organ involvement.

In this Special Issue, we aim to provide new insights into amino acid metabolism in health and disease, with an in-depth look also at D-amino acids and their role in brain “functioning and dysfunctioning”. We hope that the addressed topic will lead to a better understanding of the diverse mechanisms acting in the regulation of amino acid metabolism as well as further research studies aimed at investigating metabolic dysfunctions and their role in pathologies.


Dr. Silvia Sacchi
Guest Editor

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Published Papers (4 papers)

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15 pages, 12850 KiB  
Article
Branched-Chain Amino Acid Deprivation Decreases Lipid Oxidation and Lipogenesis in C2C12 Myotubes
by Sira Karvinen, Vasco Fachada, Ulla-Maria Sahinaho, Satu Pekkala, Juulia H. Lautaoja, Sakari Mäntyselkä, Perttu Permi, Juha J. Hulmi, Mika Silvennoinen and Heikki Kainulainen
Metabolites 2022, 12(4), 328; https://doi.org/10.3390/metabo12040328 - 5 Apr 2022
Cited by 9 | Viewed by 4376
Abstract
Impaired lipid metabolism is a common risk factor underlying several metabolic diseases such as metabolic syndrome and type 2 diabetes. Branched-chain amino acids (BCAAs) that include valine, leucine and isoleucine have been proven to share a role in lipid metabolism and hence in [...] Read more.
Impaired lipid metabolism is a common risk factor underlying several metabolic diseases such as metabolic syndrome and type 2 diabetes. Branched-chain amino acids (BCAAs) that include valine, leucine and isoleucine have been proven to share a role in lipid metabolism and hence in maintaining metabolic health. We have previously introduced a hypothesis suggesting that BCAA degradation mechanistically connects to lipid oxidation and storage in skeletal muscle. To test our hypothesis, the present study examined the effects of BCAA deprivation and supplementation on lipid oxidation, lipogenesis and lipid droplet characteristics in murine C2C12 myotubes. In addition, the role of myotube contractions on cell metabolism was studied by utilizing in vitro skeletal-muscle-specific exercise-like electrical pulse stimulation (EPS). Our results showed that the deprivation of BCAAs decreased both lipid oxidation and lipogenesis in C2C12 myotubes. BCAA deprivation further diminished the number of lipid droplets in the EPS-treated myotubes. EPS decreased lipid oxidation especially when combined with high BCAA supplementation. Similar to BCAA deprivation, high BCAA supplementation also decreased lipid oxidation. The present results highlight the role of an adequate level of BCAAs in healthy lipid metabolism. Full article
(This article belongs to the Special Issue Amino Acid Metabolism in Health and Disease)
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Review

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18 pages, 1269 KiB  
Review
Targeting Arginine in COVID-19-Induced Immunopathology and Vasculopathy
by William Durante
Metabolites 2022, 12(3), 240; https://doi.org/10.3390/metabo12030240 - 11 Mar 2022
Cited by 19 | Viewed by 4330
Abstract
Coronavirus disease 2019 (COVID-19) represents a major public health crisis that has caused the death of nearly six million people worldwide. Emerging data have identified a deficiency of circulating arginine in patients with COVID-19. Arginine is a semi-essential amino acid that serves as [...] Read more.
Coronavirus disease 2019 (COVID-19) represents a major public health crisis that has caused the death of nearly six million people worldwide. Emerging data have identified a deficiency of circulating arginine in patients with COVID-19. Arginine is a semi-essential amino acid that serves as key regulator of immune and vascular cell function. Arginine is metabolized by nitric oxide (NO) synthase to NO which plays a pivotal role in host defense and vascular health, whereas the catabolism of arginine by arginase to ornithine contributes to immune suppression and vascular disease. Notably, arginase activity is upregulated in COVID-19 patients in a disease-dependent fashion, favoring the production of ornithine and its metabolites from arginine over the synthesis of NO. This rewiring of arginine metabolism in COVID-19 promotes immune and endothelial cell dysfunction, vascular smooth muscle cell proliferation and migration, inflammation, vasoconstriction, thrombosis, and arterial thickening, fibrosis, and stiffening, which can lead to vascular occlusion, muti-organ failure, and death. Strategies that restore the plasma concentration of arginine, inhibit arginase activity, and/or enhance the bioavailability and potency of NO represent promising therapeutic approaches that may preserve immune function and prevent the development of severe vascular disease in patients with COVID-19. Full article
(This article belongs to the Special Issue Amino Acid Metabolism in Health and Disease)
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19 pages, 1519 KiB  
Review
Abnormal Iron and Lipid Metabolism Mediated Ferroptosis in Kidney Diseases and Its Therapeutic Potential
by Xiaoqin Zhang and Xiaogang Li
Metabolites 2022, 12(1), 58; https://doi.org/10.3390/metabo12010058 - 10 Jan 2022
Cited by 44 | Viewed by 6278
Abstract
Ferroptosis is a newly identified form of regulated cell death driven by iron-dependent phospholipid peroxidation and oxidative stress. Ferroptosis has distinct biological and morphology characteristics, such as shrunken mitochondria when compared to other known regulated cell deaths. The regulation of ferroptosis includes different [...] Read more.
Ferroptosis is a newly identified form of regulated cell death driven by iron-dependent phospholipid peroxidation and oxidative stress. Ferroptosis has distinct biological and morphology characteristics, such as shrunken mitochondria when compared to other known regulated cell deaths. The regulation of ferroptosis includes different molecular mechanisms and multiple cellular metabolic pathways, including glutathione/glutathione peroxidase 4(GPX4) signaling pathways, which are involved in the amino acid metabolism and the activation of GPX4; iron metabolic signaling pathways, which are involved in the regulation of iron import/export and the storage/release of intracellular iron through iron-regulatory proteins (IRPs), and lipid metabolic signaling pathways, which are involved in the metabolism of unsaturated fatty acids in cell membranes. Ferroptosis plays an essential role in the pathology of various kidneys diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), autosomal dominant polycystic kidney disease (ADPKD), and renal cell carcinoma (RCC). Targeting ferroptosis with its inducers/initiators and inhibitors can modulate the progression of kidney diseases in animal models. In this review, we discuss the characteristics of ferroptosis and the ferroptosis-based mechanisms, highlighting the potential role of the main ferroptosis-associated metabolic pathways in the treatment and prevention of various kidney diseases. Full article
(This article belongs to the Special Issue Amino Acid Metabolism in Health and Disease)
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14 pages, 1132 KiB  
Review
Which Role Plays 2-Hydroxybutyric Acid on Insulin Resistance?
by André P. Sousa, Diogo M. Cunha, Carolina Franco, Catarina Teixeira, Frantz Gojon, Pilar Baylina and Ruben Fernandes
Metabolites 2021, 11(12), 835; https://doi.org/10.3390/metabo11120835 - 3 Dec 2021
Cited by 27 | Viewed by 4494
Abstract
Type 2 Diabetes Mellitus (T2D) is defined as a chronic condition caused by beta cell loss and/or dysfunction and insulin resistance (IR). The discovering of novel biomarkers capable of identifying T2D and other metabolic disorders associated with IR in a timely and accurate [...] Read more.
Type 2 Diabetes Mellitus (T2D) is defined as a chronic condition caused by beta cell loss and/or dysfunction and insulin resistance (IR). The discovering of novel biomarkers capable of identifying T2D and other metabolic disorders associated with IR in a timely and accurate way is critical. In this review, 2-hydroxybutyric acid (2HB) is presented as that upheaval biomarker with an unexplored potential ahead. Due to the activation of other metabolic pathways during IR, 2HB is synthesized as a coproduct of protein metabolism, being the progression of IR intrinsically related to the increasing of 2HB levels. Hence, the focus of this review will be on the 2HB metabolite and its involvement in glucose homeostasis. A literature review was conducted, which comprised an examination of publications from different databases that had been published over the previous ten years. A total of 19 articles fulfilled the intended set of criteria. The use of 2HB as an early indicator of IR was separated into subjects based on the number of analytes examined simultaneously. In terms of the association between 2HB and IR, it has been established that increasing 2HB levels can predict the development of IR. Thus, 2HB has demonstrated considerable promise as a clinical monitoring molecule, not only as an IR biomarker, but also for disease follow-up throughout IR treatment. Full article
(This article belongs to the Special Issue Amino Acid Metabolism in Health and Disease)
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