Exchangeable copper and relative exchangeable copper (REC)
Exchangeable copper (CuEXC) is the fraction of plasma copper that is loosely, reversibly bound — chiefly to the N-terminal site of human serum albumin. Relative exchangeable copper (REC) is that labile pool expressed as a fraction of total serum copper:
REC (%) = exchangeable copper / total serum copper × 100
REC is a highly specific and sensitive biomarker for Wilson disease, a genetic disorder of copper metabolism. It is recommended for Wilson-disease diagnosis in the 2025 EASL-ERN Clinical Practice Guidelines on Wilson’s disease, and has been validated in large multicentre cohorts (an optimal diagnostic cut-off around 14%, with very high sensitivity and specificity).
How it is measured
- A chelator (EDTA) is added to plasma to capture the loosely bound, exchangeable copper.
- Ultrafiltration separates the exchangeable fraction.
- The copper is quantified by inductively coupled plasma mass spectrometry (ICP-MS).
- REC is calculated against total copper.
Why it matters for albuminomics
Exchangeable copper is where the albuminomics research programme began. It established the core expertise — reading disease from how metals bind to albumin, measured by ICP-MS — and the ultrafiltration + ICP-MS workflow later reused by the Serum Enhanced Binding (SEB) test, which extends the same functional-binding principle from a rare copper disorder to mass-market liver-injury diagnosis.
Frequently asked questions
What is REC used for? Diagnosing Wilson disease (including in relatives and pre-symptomatic patients) and monitoring copper-lowering therapy.
How is REC different from total or free copper? Total copper and ceruloplasmin can be normal in Wilson disease; REC specifically measures the labile, albumin-bound copper pool that best reflects copper overload.
Who developed it? Relative exchangeable copper was developed by Souleiman El Balkhi and colleagues; it is now embedded in EASL clinical practice guidance.
See also
Wilson disease · Human serum albumin · SEB test · History of the inventions · About the author