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  1. Article ; Online: Intestinal Amino Acid Transport and Metabolic Health.

    Bröer, Stefan

    Annual review of nutrition

    2023  Volume 43, Page(s) 73–99

    Abstract: Amino acids derived from protein digestion are important nutrients for the growth and maintenance of organisms. Approximately half of the 20 proteinogenic amino acids can be synthesized by mammalian organisms, while the other half are essential and must ... ...

    Abstract Amino acids derived from protein digestion are important nutrients for the growth and maintenance of organisms. Approximately half of the 20 proteinogenic amino acids can be synthesized by mammalian organisms, while the other half are essential and must be acquired from the nutrition. Absorption of amino acids is mediated by a set of amino acid transporters together with transport of di- and tripeptides. They provide amino acids for systemic needs and for enterocyte metabolism. Absorption is largely complete at the end of the small intestine. The large intestine mediates the uptake of amino acids derived from bacterial metabolism and endogenous sources. Lack of amino acid transporters and peptide transporter delays the absorption of amino acids and changes sensing and usage of amino acids by the intestine. This can affect metabolic health through amino acid restriction, sensing of amino acids, and production of antimicrobial peptides.
    MeSH term(s) Humans ; Animals ; Biological Transport ; Intestines ; Amino Acids ; Nutritional Status ; Enterocytes ; Antifibrinolytic Agents ; Mammals
    Chemical Substances Amino Acids ; Antifibrinolytic Agents
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 406980-8
    ISSN 1545-4312 ; 0199-9885
    ISSN (online) 1545-4312
    ISSN 0199-9885
    DOI 10.1146/annurev-nutr-061121-094344
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1786: Show issues Location:
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  2. Article ; Online: Amino acid transporters as modulators of glucose homeostasis.

    Bröer, Stefan

    Trends in endocrinology and metabolism: TEM

    2021  Volume 33, Issue 2, Page(s) 120–135

    Abstract: Amino acids modulate glucose homeostasis. Cytosolic levels of amino acids are regulated by amino acid transporters, modulating insulin release, protein synthesis, cell proliferation, cell fate, and metabolism. In β-cells, amino acid transporters modulate ...

    Abstract Amino acids modulate glucose homeostasis. Cytosolic levels of amino acids are regulated by amino acid transporters, modulating insulin release, protein synthesis, cell proliferation, cell fate, and metabolism. In β-cells, amino acid transporters modulate incretin-stimulated insulin release. In the liver, amino acid transporters provide glutamine and alanine for gluconeogenesis. Intestinal amino acid transporters facilitate the intake of amino acids causing protein restriction when inactive. Adipocyte development is regulated by amino acid transporters through activation of mechanistic target of rapamycin (mTORC1) and amino acid-related metabolites. The accumulation and metabolism of branched-chain amino acids (BCAAs) in muscle depends on transporters. The integration between amino acid metabolism and transport is critical for the maintenance and function of tissues and cells involved in glucose homeostasis.
    MeSH term(s) Amino Acid Transport Systems/metabolism ; Amino Acids/metabolism ; Glucose/metabolism ; Homeostasis ; Humans ; Insulin/metabolism
    Chemical Substances Amino Acid Transport Systems ; Amino Acids ; Insulin ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2021-12-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1042384-9
    ISSN 1879-3061 ; 1043-2760
    ISSN (online) 1879-3061
    ISSN 1043-2760
    DOI 10.1016/j.tem.2021.11.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2999: Show issues Location:
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  3. Book: Membrane transporter diseases

    Bröer, Stefan

    2003  

    Author's details ed. by Stefan Bröer
    Language English
    Size XI, 390 S. : Ill.
    Publisher Kluwer/Plenum
    Publishing place New York u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT013990942
    ISBN 0-306-47883-8 ; 978-0-306-47883-3
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    2004 A 2169 order for loan Magazin

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  4. Article ; Online: Amino Acid Transporters as Targets for Cancer Therapy: Why, Where, When, and How.

    Bröer, Stefan

    International journal of molecular sciences

    2020  Volume 21, Issue 17

    Abstract: Amino acids are indispensable for the growth of cancer cells. This includes essential amino acids, the carbon skeleton of which cannot be synthesized, and conditionally essential amino acids, for which the metabolic demands exceed the capacity to ... ...

    Abstract Amino acids are indispensable for the growth of cancer cells. This includes essential amino acids, the carbon skeleton of which cannot be synthesized, and conditionally essential amino acids, for which the metabolic demands exceed the capacity to synthesize them. Moreover, amino acids are important signaling molecules regulating metabolic pathways, protein translation, autophagy, defense against reactive oxygen species, and many other functions. Blocking uptake of amino acids into cancer cells is therefore a viable strategy to reduce growth. A number of studies have used genome-wide silencing or knock-out approaches, which cover all known amino acid transporters in a large variety of cancer cell lines. In this review, these studies are interrogated together with other databases to identify vulnerabilities with regard to amino acid transport. Several themes emerge, such as synthetic lethality, reduced redundancy, and selective vulnerability, which can be exploited to stop cancer cell growth.
    MeSH term(s) Amino Acid Transport Systems/drug effects ; Amino Acid Transport Systems/genetics ; Amino Acids/metabolism ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Knockout Techniques ; Gene Silencing ; Humans ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/genetics ; Signal Transduction/drug effects ; Synthetic Lethal Mutations
    Chemical Substances Amino Acid Transport Systems ; Amino Acids ; Antineoplastic Agents
    Language English
    Publishing date 2020-08-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21176156
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Amino Acid Transporters as Disease Modifiers and Drug Targets.

    Bröer, Stefan

    SLAS discovery : advancing life sciences R & D

    2018  Volume 23, Issue 4, Page(s) 303–320

    Abstract: Amino acids perform a variety of functions in cells and organisms, particularly in the synthesis of proteins, as energy metabolites, neurotransmitters, and precursors for many other molecules. Amino acid transport plays a key role in all these functions. ...

    Abstract Amino acids perform a variety of functions in cells and organisms, particularly in the synthesis of proteins, as energy metabolites, neurotransmitters, and precursors for many other molecules. Amino acid transport plays a key role in all these functions. Inhibition of amino acid transport is pursued as a therapeutic strategy in several areas, such as diabetes and related metabolic disorders, neurological disorders, cancer, and stem cell biology. The role of amino acid transporters in these disorders and processes is well established, but the implementation of amino acid transporters as drug targets is still in its infancy. This is at least in part due to the underdeveloped pharmacology of this group of membrane proteins. Recent advances in structural biology, membrane protein expression, and inhibitor screening methodology will see an increased number of improved and selective inhibitors of amino acid transporters that can serve as tool compounds for further studies.
    MeSH term(s) Amino Acid Transport Systems/metabolism ; Amino Acids/metabolism ; Animals ; COS Cells ; Cell Line ; Chlorocebus aethiops ; Drug Delivery Systems/methods
    Chemical Substances Amino Acid Transport Systems ; Amino Acids
    Language English
    Publishing date 2018-03-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1177/2472555218755629
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Amino Acid Homeostasis in Mammalian Cells with a Focus on Amino Acid Transport.

    Bröer, Stefan / Gauthier-Coles, Gregory

    The Journal of nutrition

    2021  Volume 152, Issue 1, Page(s) 16–28

    Abstract: Amino acid homeostasis is maintained by import, export, oxidation, and synthesis of nonessential amino acids, and by the synthesis and breakdown of protein. These processes work in conjunction with regulatory elements that sense amino acids or their ... ...

    Abstract Amino acid homeostasis is maintained by import, export, oxidation, and synthesis of nonessential amino acids, and by the synthesis and breakdown of protein. These processes work in conjunction with regulatory elements that sense amino acids or their metabolites. During and after nutrient intake, amino acid homeostasis is dominated by autoregulatory processes such as transport and oxidation of excess amino acids. Amino acid deprivation triggers processes such as autophagy and the execution of broader transcriptional programs to maintain plasma amino acid concentrations. Amino acid transport plays a crucial role in the absorption of amino acids in the intestine, the distribution of amino acids across cells and organs, the recycling of amino acids in the kidney, and the recycling of amino acids after protein breakdown.
    MeSH term(s) Amino Acids/metabolism ; Animals ; Autophagy ; Biological Transport ; Homeostasis ; Oxidation-Reduction
    Chemical Substances Amino Acids
    Language English
    Publishing date 2021-10-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218373-0
    ISSN 1541-6100 ; 0022-3166
    ISSN (online) 1541-6100
    ISSN 0022-3166
    DOI 10.1093/jn/nxab342
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  7. Article: Inhibition of GCN2 Reveals Synergy with Cell-Cycle Regulation and Proteostasis.

    Gauthier-Coles, Gregory / Rahimi, Farid / Bröer, Angelika / Bröer, Stefan

    Metabolites

    2023  Volume 13, Issue 10

    Abstract: The integrated stress response is a signaling network comprising four branches, each sensing different cellular stressors, converging on the phosphorylation of eIF2α to downregulate global translation and initiate recovery. One of these branches includes ...

    Abstract The integrated stress response is a signaling network comprising four branches, each sensing different cellular stressors, converging on the phosphorylation of eIF2α to downregulate global translation and initiate recovery. One of these branches includes GCN2, which senses cellular amino acid insufficiency and participates in maintaining amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is induced by inhibiting an additional target. In this light, we screened numerous drugs for their potential to synergize with the GCN2 inhibitor TAP20. The drug sensitivity of six cancer cell lines to a panel of 25 compounds was assessed. Each compound was then combined with TAP20 at concentrations below their IC
    Language English
    Publishing date 2023-10-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo13101064
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  8. Article ; Online: Do Amino Acid Antiporters Have Asymmetric Substrate Specificity?

    Gauthier-Coles, Gregory / Fairweather, Stephen J / Bröer, Angelika / Bröer, Stefan

    Biomolecules

    2023  Volume 13, Issue 2

    Abstract: Amino acid antiporters mediate the 1:1 exchange of groups of amino acids. Whether substrate specificity can be different for the inward and outward facing conformation has not been investigated systematically, although examples of asymmetric transport ... ...

    Abstract Amino acid antiporters mediate the 1:1 exchange of groups of amino acids. Whether substrate specificity can be different for the inward and outward facing conformation has not been investigated systematically, although examples of asymmetric transport have been reported. Here we used LC-MS to detect the movement of
    MeSH term(s) Amino Acids/metabolism ; Substrate Specificity ; Antiporters/metabolism ; Proline/metabolism ; Biological Transport
    Chemical Substances Amino Acids ; Antiporters ; Proline (9DLQ4CIU6V)
    Language English
    Publishing date 2023-02-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom13020301
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  9. Article ; Online: Impact of Inhibition of Glutamine and Alanine Transport on Cerebellar Glial and Neuronal Metabolism.

    Das, Abhijit / Gauthier-Coles, Gregory / Bröer, Stefan / Rae, Caroline D

    Biomolecules

    2022  Volume 12, Issue 9

    Abstract: The cerebellum, or "little brain", is often overlooked in studies of brain metabolism in favour of the cortex. Despite this, anomalies in cerebellar amino acid homeostasis in a range of disorders have been reported. Amino acid homeostasis is central to ... ...

    Abstract The cerebellum, or "little brain", is often overlooked in studies of brain metabolism in favour of the cortex. Despite this, anomalies in cerebellar amino acid homeostasis in a range of disorders have been reported. Amino acid homeostasis is central to metabolism, providing recycling of carbon backbones and ammonia between cell types. Here, we examined the role of cerebellar amino acid transporters in the cycling of glutamine and alanine in guinea pig cerebellar slices by inhibiting amino acid transporters and examining the resultant metabolism of [1-
    MeSH term(s) Acetates/metabolism ; Alanine/metabolism ; Alanine/pharmacology ; Ammonia/metabolism ; Animals ; Carbon/metabolism ; Cerebellum/metabolism ; Glucose/metabolism ; Glutamates/metabolism ; Glutamic Acid/metabolism ; Glutamine/metabolism ; Guinea Pigs ; Histidine/metabolism
    Chemical Substances Acetates ; Glutamates ; Glutamine (0RH81L854J) ; Glutamic Acid (3KX376GY7L) ; Histidine (4QD397987E) ; Carbon (7440-44-0) ; Ammonia (7664-41-7) ; Glucose (IY9XDZ35W2) ; Alanine (OF5P57N2ZX)
    Language English
    Publishing date 2022-08-27
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom12091189
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  10. Article ; Online: Diseases associated with general amino acid transporters of the solute carrier 6 family (SLC6).

    Broer, Stefan

    Current molecular pharmacology

    2013  Volume 6, Issue 2, Page(s) 74–87

    Abstract: Amino acid transporters of the SLC6 family mediate the Na(+)-dependent uptake of neutral amino acids into neurons and epithelial cells of the intestine, kidney and other organs. They are integral parts of amino acid homeostasis in the whole body and the ... ...

    Abstract Amino acid transporters of the SLC6 family mediate the Na(+)-dependent uptake of neutral amino acids into neurons and epithelial cells of the intestine, kidney and other organs. They are integral parts of amino acid homeostasis in the whole body and the brain. In the intestine they are involved in protein absorption, while in the kidney they regulate plasma amino acid concentrations through reabsorption. The metabolic role of SLC6 amino acid transporters in the brain is less clear and most likely related to anaplerosis of the TCA cycle. Mutations in these transporters cause rare inherited disorders such as Hartnup disorder and iminoglycinuria. They may also play a role in complex traits such as depression, anxiety, obesity, diabetes and cancer. The review does not cover the transport of neurotransmitter amino acids.
    MeSH term(s) Amino Acid Transport Systems, Neutral/chemistry ; Amino Acid Transport Systems, Neutral/genetics ; Amino Acid Transport Systems, Neutral/metabolism ; Animals ; Diabetes Mellitus/genetics ; Diabetes Mellitus/metabolism ; Humans ; Models, Molecular ; Mutation ; Neoplasms/genetics ; Neoplasms/metabolism ; Obesity/genetics ; Obesity/metabolism ; Protein Conformation
    Chemical Substances Amino Acid Transport Systems, Neutral
    Language English
    Publishing date 2013-05-09
    Publishing country United Arab Emirates
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1874-4702
    ISSN (online) 1874-4702
    DOI 10.2174/18744672113069990034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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