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Nutrients 2017, 9(9), 1035; doi:10.3390/nu9091035

Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis

Laboratory of Nutrition, Faculty of Pharmacy, University Louis Pasteur, F-67401 Strasbourg, France
Received: 21 August 2017 / Revised: 14 September 2017 / Accepted: 16 September 2017 / Published: 20 September 2017
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Abstract

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. View Full-Text
Keywords: lean body mass; transthyretin; protein malnutrition; inflammatory disorders; methionine pool size; cystathionine-β-synthase; homocysteine; sarcopenia lean body mass; transthyretin; protein malnutrition; inflammatory disorders; methionine pool size; cystathionine-β-synthase; homocysteine; sarcopenia
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Ingenbleek, Y. Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis. Nutrients 2017, 9, 1035.

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