Table 1. Albumin Adducts Found in Vivo.
| compound | analysis | workup | albumin adduct |
|---|---|---|---|
| Aflatoxin B1 (AFB) | HPLC-fa, ELISA LC-MS/MS | Pronase | The major adduct = AFB-Lys in rats and human (Figure 8).71,101,115,120,203,205,207 Trypsin digest of in vitro modified bovine Alb yielded adducts with Lys455 and Lys548.201 |
| Aflatoxin G1 (AFG) | HPLC-f, ELISA | Pronase | Determination of the Alb adduct with lysine in rats: AFG-Lys.209 |
| N-Acetyl-4-aminophenol | LC-MS/MS | Pronase | N-Acetyl-p-benzoquinoneimine-Cys-Pro-Phe in humans (Figure 15,16).116 |
| 4,4′-Methylenediphenyl diisocyanate (MDI) | LC-MS/MS | Pronase | MDI-Lys and AcMDI-Lys in rats,121 and humans (Figure 8).106 |
| 2,4- and 2,6-toluene diisocyanate (TDI) | LC-MS/MS | Pronase | 3A4MP-Lys, 5A2MP-Lys, and 3A2MP-Lys in humans (Figure 8).232 |
| Isothiocyanates (ITC) released from glucusinolates | LC-MS/MS | Pronase | Phenethyl-ITC-Lys, benzyl-ITC-Lys, allyl-ITC-Lys, sulforaphane-Lys (Figure 13),269,270 and 1-methoxy-3-indolylmethyl glucosinolate Nτ-(1-methoxy-3-indolylmethyl)-His adducts in mice.323 |
| Benzene (B) | GC-MS | Raney-nickel derivatization | Raney-nickel cleaves Cys-bound benzene (B): 1,2-BQ-Cys → catechol,3241,4-BQ-Cys → hydroquinone (Figure 5)324 Hydrolysis and derivatization of benzene oxide (BO)-Cys, 1,2-BQ-Cys, and 1,4-BQ-Cys yields phenyltrifluorothioacetate,99O,O′,S-tris-trifluoroacetyl-catechol,172 and O,O′,S-tris-trifluoroacetyl-hydroquinone, respectively. |
| Pentachlorophenol | GC-MS | Raney-nickel | Tetrachloro-1,4-benzoquinone-Cys → Raney-nickel, adducts in rats.325 |
| Styrene | GC-MS | Raney-nickel | Adducts of styrene-7,8-oxide with Cys, Raney-nickel cleavage yields 1-phenylethanol and 2-phenylethanol in rats and workers.98,185 |
| Naphthalene | GC-MS | Hydrolysis, derivatization | Reaction with methanesulfonic acid and trifluoroacetic acidanhydride yields derivatives of 1-sulfanyl- dihydronaphthalene-2-ol (NPOS1), 2-sulfanyl-1,2-dihydronaphthalene-1-ol (NPOS2), 4-sulfanyl-1,2-naphthalene-1,2-diol (1,2-NPQ-4S), and 2-sulfanyl-1,4-naphthalene-1,4-diol (1,4-NPQ-2S) (Figure S1).179 NPOS1 is the major adduct in rats,179 mice,100 1,2-NPQ, and 1,4NPQ adducts in humans.181 |
| Tetrachloroethene (PER)326 | GC-MS | Hydrolysis, derivatization | Rats exposed to 40 ppm PER for 6 h and 0.35–0.48 pmol N-(dichloroacetyl)-l-(dichloroacetyl)-l-lysine/mg plasma proteins (PP). |
| Sulfur mustard | LC-MS/MS | Pronase, Trypsin | Pronase treatment of Alb, S-[2-[(hydroxyethyl)thio]ethyl];Cys-Pro-Phe was found in human samples (Figure 12).315 The tryptic fragment ALVLIAFAQYLQQCPFEDHVK of in vitro modified Alb contains the cysteine adduct.327,328 Detection of this adduct did not succeed in human samples.258 |
| Chlorpyrifos and/or diazinon329 | LC-MS/MS | Pronase | Tyrosine diethylphosphothioate and tyrosine diethylphosphoro-adduct in a patient that had ingested chlorpyrifos.330 |
| Dichlorvos130 | LC-MS/MS | Pepsin | In two suicidal patients using dichlorvos, tyrosine-dimethoxyphosphate (Tyr411) was identified in Alb peptides VRY411TKKVPQVSTPTL and LVRY411TKKVPQVSTPTL. |
| Sarin, soman, tabun, and cyclosarin247 | LC-MS/MS | Pronase | Tyrosine-adduct in guinea pigs. |
| Alcohol | ELISA | Immune response to acetaldehyde-human serum Alb adduct among healthy subjects related to alcohol intake.331 | |
| Oxidative stress: 3-nitro-tyrosine332 | LC-MS/MS | Acid hydrolysis | 3-Nitro-tyrosine was found in Alb from rats. |
| Oxidative stress: malondialdehyde49 | LC-MS/MS | In patients with idiopathic pulmonary arterial hypertension, pulmonary hypertension,and sickle cell anemia LC-MS/MS adduct with Lys-159. | |
| Oxidative stress: malondialdehyde299 | UV/vis | Derivatization whole protein | Ischemia/reperfusion damage of Alb in patients; protein carbonylation was measured after dervatization with 2,4-dinitrophenylhydrazine (DNPH).308 |
| Oxidative stress: acrolein299 | LC-MS/MS | Trypsin + chymotrypsin | Ischemia/reperfusion damage of Alb in patients; the adduct-level of LQQC(acrolein)PF in Alb increased from 0.6 ± 0.4% to 2.3 ± 0.7%; after 10 min of reperfusion. |
| Oxidative stress: ischemia modified Alb (IMA)333,334 | Cobalt-binding test | IMA relates to the decreased binding capacity of Alb for cobalt. In 283 healthy subjects, IMA ranged from 52.8 to 116.6 U/mL. Cut-off value for normal vs high IMA = 85 U/mL. For nonpathologic conditions, IMA is ca. 1–2% of the total Alb concentration and 6–8% in patients with ischemia. | |
| Oxidative stress: carbonylation; chronic arthritis | UV/vis | Derivatization whole protein | Carbonylated plasma proteins of children with different forms of juvenile chronic arthritis determined after derivatization with DNPH; carbonylation level was significantly higher than that in the healthy group (1.36 ± 0.68 vs 0.81 ± 0.16 nmol carbonyl/mg of protein).335 |
| Oxidative stress: carbonylation; chronic renal failure | UV/vis | Derivatization whole protein | Carbonylation levels in patients with chronic renal failure (13.7 ± 4.5 μmol/L) measured after derivatization with DNPH was higher than that in normal volunteers (0.76 ± 0.51 μmol/L), and higher than that in patients on chronic maintenance hemodialysis (16.95 ± 2.62 μmol/L).336 |
| Oxidative stress: cysteinylation | LC-MS/MS | Trypsin + chymotrypsin | Cysteinylation measured as LQQC(Cys)PF is significantly increased in end stage renal disease patients.7 |
a
HPLC-fluorescence (HPLC-f).