Editorial

Tsikas, Dimitrios

doi:10.1007/s00726-022-03164-2

Cited by 3 publications

(1 citation statement)

References 21 publications

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“…Amino acid residues in proteins undergo post-translational modifications (PTM) (Tsikas 2021 , 2022 ). Metformin use has been associated with changes in concentrations of amino acids and their metabolites (Preiss et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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

Baskal,

Posma,

Bollenbach

et al. 2024

Amino Acids

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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.

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Section: Introductionmentioning

confidence: 99%

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

Baskal,

Posma,

Bollenbach

et al. 2024

Amino Acids

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Possible role of SIRT1 and SIRT3 in post-translational modifications in human breast milk during the neonatal period

et al. 2022

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We measured free and proteinic concentrations of native and modified amino acids from post-translational modifications (PTMs) and correlated them with the activity of SIRT1 and SIRT3 in the pellet and aqueous phases of human breast milk samples of ten lactating women during the neonatal period. SIRT1 and SIRT3 correlated directly with citrullination, asymmetric dimethylation and glycation of L-arginine, hydroxylation and glycation of L-lysine. SIRT1 and SIRT3 correlated inversely with the hydroxylation of L-proline. SIRT1 and SITR3 tended to correlate inversely with oxidative stress measured as malondialdehyde. Our study suggests that SIRT1 and SIRT3 may modulate PTMs in human breast milk cells.

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Malondialdehyde-Induced Post-Translational Modification of Human Hemoglobin

Tsikas

2023

J. Proteome Res.

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Lysine residues in proteins undergo multiple enzymatic and nonenzymatic post-translational modifications (PTMs). The terminal ε amine group of lysine residues in proteins is carbonylated chemically by carbonyl species such as glyoxal (GO; OCH–CHO, C2H2O2; MW 58) and methylglyoxal (MGO; OCH-C(=O)–CH3, C3H4O2; MW 72) that are derived from the metabolism of endogenous substances including glucose. The dicarbonyl species malondialdehyde (MDA, OCH–CH2–CHO, C3H4O2; MW 72) is generated by enzymatic and nonenzymatic peroxidation of polyunsaturated fatty acids (PUFAs). GO, MGO, and MDA occur in biological systems in their free forms and in their conjugated forms adducted to free amino acids and amino acid residues in proteins, notably to lysine. MDA is a C–H-acidic acid (pK a, 4.45). Biological MDA is widely used as a biomarker of lipid peroxidation. The most frequently analyzed biological samples for MDA are plasma and serum. Reportedly, MDA concentrations in plasma and serum samples of healthy and ill humans range by several orders of magnitude. The most severe preanalytical contributor is artificial formation of MDA in lipid-rich samples such as plasma and serum. In very few publications, plasma MDA concentrations were reported to lie in the lower mM-range.

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Editorial

Cited by 3 publications

References 21 publications

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

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

Possible role of SIRT1 and SIRT3 in post-translational modifications in human breast milk during the neonatal period

Malondialdehyde-Induced Post-Translational Modification of Human Hemoglobin

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