THE MODIFICATION
A persistent chemical modification of lysine
What CML is
CML — Nε-carboxymethyl-lysine — is an advanced glycation end-product (AGE): a stable chemical modification in which a carboxymethyl group is attached to the side-chain nitrogen of a lysine residue. It forms non-enzymatically, through ordinary chemistry between sugars, their oxidation products and proteins — no enzyme is required, and no biological programme controls it.
Where it accumulates
Because the reaction is slow but effectively irreversible, CML builds up preferentially on long-lived proteins — the proteins that are not regularly replaced. It is associated with the chemical ageing of collagen and the extracellular matrix, the structural framework that gives tissues their mechanical properties.
It is not chemically inert
CML can act as a signal through RAGE, the receptor for advanced glycation end-products, linking accumulated chemical damage to cellular responses. It is chemically different from glucosepane — another important AGE cross-link — and it is not just glucose temporarily attached to a protein: it is a stable, rearranged structure.
Prevention is not removal
Most glycation strategies operate before or during damage formation. None of them remove the CML that has already accumulated on long-lived proteins. That distinction is the scientific opening that enzymatic deglycation — and the CMLase research programme — addresses.
| Approach | Target | Timing | Purpose |
|---|---|---|---|
| Carbonyl control | Reactive precursors | Before damage | Reduce new glycation |
| Glycation inhibition | Early reactions | During formation | Slow accumulation |
| Enzymatic deglycation | Existing CML | After formation | Restore lysine |