N(6)-carboxymethyllysine

N(6)-carboxymethyllysine (CML), also known as N(6)-(carboxymethyl)lysine, is an advanced glycation end-product (AGE) that is formed during the Maillard reaction. It is a non-enzymatic reaction between reducing sugars and amino acids, proteins, or lipids. CML is one of the most abundant and well-studied AGEs.

Formation and Structure

CML is formed through the Maillard reaction, a non-enzymatic browning reaction that occurs during cooking and processing of foods. The reaction begins with the condensation of a reducing sugar and an amino group, forming a Schiff base. This base then undergoes rearrangement to form an Amadori product, which can further react to form various AGEs, including CML.

The structure of CML consists of a lysine residue that has been modified by the addition of a carboxymethyl group at the 6 position of the lysine amino acid. This modification results in a molecule with increased polarity and reactivity compared to the original lysine residue.

Biological Significance

CML is a major AGE that accumulates in human tissues during aging and under conditions of oxidative stress and inflammation. It has been implicated in the pathogenesis of several age-related diseases, including diabetes, cardiovascular disease, Alzheimer's disease, and kidney disease.

CML can interact with specific cell surface receptors, such as the receptor for advanced glycation end products (RAGE), leading to the activation of intracellular signaling pathways and the production of pro-inflammatory and pro-oxidant molecules. This can contribute to tissue damage and disease progression.

Detection and Measurement

CML can be detected and quantified in biological samples using various analytical techniques, such as immunoassays, mass spectrometry, and high-performance liquid chromatography (HPLC). These methods allow for the measurement of CML in blood, urine, and tissue samples, providing a means to assess AGE accumulation in the body.

See Also

• Advanced glycation end-product
• Maillard reaction
• Diabetes
• Cardiovascular disease
• Alzheimer's disease
• Kidney disease