دورية أكاديمية
أعرض في EDS

GC-MS analysis of 4-hydroxyproline: elevated proline hydroxylation in metformin-associated lactic acidosis and metformin-treated Becker muscular dystrophy patients.

التفاصيل البيبلوغرافية
العنوان: GC-MS analysis of 4-hydroxyproline: elevated proline hydroxylation in metformin-associated lactic acidosis and metformin-treated Becker muscular dystrophy patients.
المؤلفون: Baskal S; Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany., Posma RA; Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Bollenbach A; Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany., Dieperink W; Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Bakker SJL; Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Nijsten MW; Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Touw DJ; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Tsikas D; Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. tsikas.dimitros@mh-hannover.de.
المصدر: Amino acids [Amino Acids] 2024 Mar 10; Vol. 56 (1), pp. 21. Date of Electronic Publication: 2024 Mar 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer-Verlag Country of Publication: Austria NLM ID: 9200312 Publication Model: Electronic Cited Medium: Internet ISSN: 1438-2199 (Electronic) Linking ISSN: 09394451 NLM ISO Abbreviation: Amino Acids Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Wien ; New York : Springer-Verlag, c1991-
مواضيع طبية MeSH: Metformin*/adverse effects , Diabetes Mellitus, Type 2*/drug therapy , Acidosis, Lactic*/chemically induced , Acidosis, Lactic*/therapy , Muscular Dystrophy, Duchenne*/drug therapy, Humans ; Hydroxyproline ; Gas Chromatography-Mass Spectrometry ; Proline ; Hydroxylation ; Lactic Acid ; Mixed Function Oxygenases/therapeutic use ; Hypoglycemic Agents/adverse effects
مستخلص: Metformin (N,N-dimethylbiguanide), an inhibitor of gluconeogenesis and insulin sensitizer, is widely used for the treatment of type 2 diabetes. In some patients with renal insufficiency, metformin can accumulate and cause lactic acidosis, known as metformin-associated lactic acidosis (MALA, defined as lactate ≥ 5 mM, pH < 7.35, and metformin concentration > 38.7 µM). Here, we report on the post-translational modification (PTM) of proline (Pro) to 4-hydroxyproline (OH-Pro) in metformin-associated lactic acidosis and in metformin-treated patients with Becker muscular dystrophy (BMD). Pro and OH-Pro were measured simultaneously by gas chromatography-mass spectrometry before, during, and after renal replacement therapy in a patient admitted to the intensive care unit (ICU) because of MALA. At admission to the ICU, plasma metformin concentration was 175 µM, with a corresponding lactate concentration of 20 mM and a blood pH of 7.1. Throughout ICU admission, the Pro concentration was lower compared to healthy controls. Renal excretion of OH-Pro was initially high and decreased over time. Moreover, during the first 12 h of ICU admission, OH-Pro seems to be renally secreted while thereafter, it was reabsorbed. Our results suggest that MALA is associated with hyper-hydroxyprolinuria due to elevated PTM of Pro to OH-Pro by prolyl-hydroxylase and/or inhibition of OH-Pro metabolism in the kidneys. In BMD patients, metformin, at the therapeutic dose of 3 × 500 mg per day for 6 weeks, increased the urinary excretion of OH-Pro suggesting elevation of Pro hydroxylation to OH-Pro. Our study suggests that metformin induces specifically the expression/activity of prolyl-hydroxylase in metformin intoxication and BMD.
(© 2024. The Author(s).)
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فهرسة مساهمة: Keywords: 4-Hydroxyproline; Amino acids; BMD; Dialysis; GC–MS; Intoxication; Kidney injury; MALA; Mass spectrometry; PTM; Renal replacement therapy (RTR)
المشرفين على المادة: 9100L32L2N (Metformin)
RMB44WO89X (Hydroxyproline)
9DLQ4CIU6V (Proline)
33X04XA5AT (Lactic Acid)
EC 1.- (Mixed Function Oxygenases)
0 (Hypoglycemic Agents)
تواريخ الأحداث: Date Created: 20240310 Date Completed: 20240312 Latest Revision: 20240313
رمز التحديث: 20240313
مُعرف محوري في PubMed: PMC10925573
DOI: 10.1007/s00726-024-03383-9
PMID: 38461423
قاعدة البيانات: MEDLINE
الوصف
تدمد:1438-2199
DOI:10.1007/s00726-024-03383-9