Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis
Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes under...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-09-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/9/9/1035 |
| _version_ | 1811316308712620032 |
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| author | Yves Ingenbleek |
| author_facet | Yves Ingenbleek |
| author_sort | Yves Ingenbleek |
| collection | DOAJ |
| description | Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value. |
| first_indexed | 2024-04-13T11:46:43Z |
| format | Article |
| id | doaj.art-ec8d179895ea411e835f74f668b339ef |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-04-13T11:46:43Z |
| publishDate | 2017-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-ec8d179895ea411e835f74f668b339ef2022-12-22T02:48:10ZengMDPI AGNutrients2072-66432017-09-0199103510.3390/nu9091035nu9091035Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine HomeostasisYves Ingenbleek0Laboratory of Nutrition, Faculty of Pharmacy, University Louis Pasteur, F-67401 Strasbourg, FranceProtein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value.https://www.mdpi.com/2072-6643/9/9/1035lean body masstransthyretinprotein malnutritioninflammatory disordersmethionine pool sizecystathionine-β-synthasehomocysteinesarcopenia |
| spellingShingle | Yves Ingenbleek Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis Nutrients lean body mass transthyretin protein malnutrition inflammatory disorders methionine pool size cystathionine-β-synthase homocysteine sarcopenia |
| title | Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis |
| title_full | Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis |
| title_fullStr | Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis |
| title_full_unstemmed | Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis |
| title_short | Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis |
| title_sort | lean body mass harbors sensing mechanisms that allow safeguarding of methionine homeostasis |
| topic | lean body mass transthyretin protein malnutrition inflammatory disorders methionine pool size cystathionine-β-synthase homocysteine sarcopenia |
| url | https://www.mdpi.com/2072-6643/9/9/1035 |
| work_keys_str_mv | AT yvesingenbleek leanbodymassharborssensingmechanismsthatallowsafeguardingofmethioninehomeostasis |