How Does ΔS‑Cys‑Albumin Work?Click Me for Full Story
Once plasma or serum is exposed to air, its most abundant protein (albumin) gets oxidized via a process known as S‑Cysteinylation. This is a slow process that can take a few days at room temperature, but in which most progress occurs early on. Once complete, the percentage of albumin in the S‑Cysteinylated form will have increased from what it was in a fresh sample by about 20%. This increase in S‑Cysteinylation from an initial measurement is known as ΔS‑Cys‑Albumin and it gets very small (going to zero)
if a sample has already been exposed to thawed conditions prior to an initial measurement. We measure the percentage of S‑Cysteinylated Albumin using mass spectrometric analysis of the intact protein: once before and once after an intentional overnight incubation of the sample at 37 °C / 98 F that drives the S‑Cysteinylation process to completion (see figure below).
ΔS‑Cys‑Albumin from Start to Finish
Part a) Biochemical reactions that underlie the ΔS-Cys-Albumin marker. Part b) Half a microliter of plasma or serum is diluted 1000‑fold and injected onto a liquid chromatograph‑mass spectrometer (LC‑MS) for analysis of intact albumin (brown spectrum) and determination of the percentage of albumin that is S‑cysteinylated (oxidized). A 9.5‑μL aliquot of the same sample is then intentionally incubated at 37 °C for 18 hrs to drive the percentage of albumin in the S-cysteinylated form to its maximum possible value—which is always less than 100%—and the sample is measured once again (blue spectrum). The difference between the two measurements, known as “ΔS‑Cys‑Albumin”, is in the range of 12-29% for fresh plasma samples (10-24% for serum) and as low as zero for samples that have been exposed to thawed conditions (> ‑30 °C for prolonged periods of time). Since we have also established the multi-reaction rate law for formation of S-cysteinylated albumin at room temperature, measurements of ΔS-Cys-Albumin are quantitatively linked to time of exposure to the equivalent of room temperature (right-hand panel).
