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Targeted Metabolomics Services

N(6)-Carboxy-methyllysine

CML
Updated 20/12/2022

What is measured?

N(epsilon)-(carboxymethyl)lysine, (2S)-2-amino-6-(carboxymethylamino)hexanoic acid.
Method(s): GC-MS/MS (1).

What is N(6)-carboxymethyllysine?

N(ε)-(carboxymethyl)lysine (CML) is one of the major advanced glycation end products (AGEs). These are generated by the Maillard reaction (MR) during thermal treatment of foods or are formed in vivo by nonenzymatic chemical reactions, taking place in tissues or fluid where significant concentration of glucose, fructose, or more reactive dicarbonyls react with proteins. CML is formed by oxidation of fructosyl-lysine (an Amadori product) (the AGE path) and the direct reaction of glyoxal, produced during lipid peroxidation, with the ε-amino group of lysine (the ALE path). CML and other AGEs in tissues and serum/plasma increase with age, and have been assigned a role in the pathogenesis of age-related, chronic diseases, including diabetes, cardiovascular disease, Alzheimer’s disease and renal dysfunction (2, 3).

Indication(s)

Assessment of AGEs status.

Specimen, collection and processing

Patient/subject: No special precaution.
Matrix: Serum or EDTA plasma.
Volume: Minimum volume is 50 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: Stable.

Transportation

Frozen, on dry ice. (for general instruction on transportation, click here)

Reported values, interpretation

Reported values: 0.05-0.30 µmol/L
Intraclass correlation coefficient (ICC): na.

 

Literature

1. Midttun, Ø., McCann, A., Aarseth, O., Krokeide, M., Kvalheim, G., Meyer, K., and Ueland, P.M. (2016). Combined measurement of 6 fat-soluble vitamins and 26 water-soluble functional vitamin markers and amino acids in 50 μL of serum or plasma by high-throughput mass spectrometry. Anal Chem 88, 10427-436.
2. Chaudhuri, J., Bains, Y., Guha, S., Kahn, A., Hall, D., Bose, N., Gugliucci, A., and Kapahi, P. (2018). The role of advanced glycation end products in aging and metabolic diseases: Bridging association and causality. Cell Metab 28, 337-352.
3. Brings, S., Fleming, T., Freichel, M., Muckenthaler, M.U., Herzig, S., and Nawroth, P.P. (2017). Dicarbonyls and advanced glycation end-products in the development of diabetic complications and targets for intervention. Int J Mol Sci 18, 984.

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Cardiometabolic
Inflammation
Microbiome
Nutrition
Categories

Amino acids, amino acid catabolites, acylcarnitines, TCA metabolites, ketone bodies, AGEs



Kynurenines, ratio-derived metabolites, proteins





SCFAs, indoles, choline metabolites, amino acid derived





B-vitamins, functional markers, and methyl donors, fat-soluble vitamins, essential amino acids, meat & fish intake, tobacco use & coffee intake
Biomarkers (n)
65
19
20
41
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Amino acids: Alanine, Arginine, Asparagine, Aspartic acid, Glutamic acid, Glutamine, Glycine, Histidine, Isoleucine, Kynurenine, Leucine, Lysine, Methionine, Ornithine, Phenylalanine, Proline, Sarcosine, Serine, Threonine, Total cysteine, Tryptophan, Tyrosine, Valine

Amino acid catabolites: 2-Aminoadipic acid, 2-Hydroxybutyrate, 3-Hydroxysiobutyrate, α-Hydroxyglutaric acid, β-Alanine, β-Aminoisobutyrate, β-Hydroxy B-methylbutyric acid, Phenylacetylglutamine

Acylcarnities: BB, C0, C2, C3, C3-DC, C4, C4-OH, C4-DC, iC5, C5-DC, C5:1, C6, C8, C10, C12, C14, C14-OH, C16, C16-OH, C18, C18-OH, C18:1, C18:2

TCA metabolites: α-Ketoglutarate, Citrate, Fumarate, Isocitrate, Lactate, Malate, Pyruvate

Ketone bodies: Acetoacetate, 3-Hydroxybutyrate

AGEs: Carboxyethyllysine, Carboxymethyllysine

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Kynurenines: 3-hydroxykynurenine, 3-hydroxyanthranilic acid, Anthranilic acid, Kynurenine, Kynurenic acid, Nicotinic acid, Nicotinamide, N1-methylnicotinamide, Picolinic acid, Quinaldic acid, Quinolinic acid, Xanthurenic acid

Neopterin

Proteins: C-Reactive protein, Calprotectin, Serum Amyloid A

Ratio-derived: Kynurenine/tryptophan ratio, PAr index (PLP, PL, PA)

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SCFAs: Acetate, Butyrate, Formate, Isobutyrate, Isovalerate, Propionate, Valerate, α-Methylbutyrate

Indoles: 3-Indoxyl sulfate, Imidazole propionate, Indole-3-acetamide, Indole-3-acetate, Indole-3-aldehyde, Indole-3-lactate, Indole-3-propionate

Choline metabolites: Choline, Betaine, DMG, TMAO

Amino acid derived: Phenylacetylglutamine

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B-vitamins, functional markers, and methyl donors: 4-Pyridoxic acid, Betaine, Choline, Cobalamin, Flavin mononucleotide, Folate, Methylmalonic acid, N1-methylnicotinamide, Nicotinamide, Nicotinic acid, Pyridoxal, Pyridoxal 5-phosphate, Pyridoxine, Riboflavin, Thiamine, Thiamine monophosphate, Total homocysteine

Fat-soluble vitamins: 25-hydroxy vitamin D2, 25-hydroxy vitamin D3, α-Tocopherol (Vit. E), All-trans retinol (Vit. A), Phylloquinone (Vit. K1), y-Tocopherol (Vit. E)

Essential amino acids: Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine

Meat and fish intake: 1-Methylhistidine, 3-Methylhistidine, B-Alanine, Creatine, Creatinine, TMAO

Tobacco use and coffee intake: Cotinine, Trans-3-hydroxycotinine, Trigonelline

Volume (μl)
200
150
250
300
Analytical techniques
GC- and LC-MS/MS
LC- and MALDI-MS
GC- and LC-MS/MS
GC- and LC-MS/MS

Turnaround time

2-6 weeks, depending on number of samples and laboratory capacity.
Please contact us for a projected time estimate specific to your project.

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