Comparative studies on the heterogeneity of plasma-derived and recombinant human albumins in laboratory use

Differences in Esterase Activity to Aspirin and <i>p</i>-Nitrophenyl Acetate among Human Serum Albumin Preparations

“…As with the report of Minami et al, 29) sulfhydryl contents of 090M7001V and SLBD7204V were higher than those of 113K7601 and 085K7541. Coupling between fatty acid binding and sulfhydryl oxidation was also observed as with in bovine serum albumin, 26) although the hydrolysis for p-nitrophenyl acetate was not decreased unlike the report of Anraku et al 30) Fatty acid binding to HSA induces conformational changes, 31) and the presence of up to 3 mol fatty acids/mol HSA or 8 mol fatty acids/mol HSA has been shown to enhance the binding of warfarin or aspirin to HSA in subdomain IIA, respectively.…”

Quantitation of Oxidative Modifications of Commercial Human Albumin for Clinical Use

“…Furthermore, HNA has been classified into two types; the major part of HNA, the disulfide product, is the "reversibly" oxidized form, while the minor part is the "irreversibly" oxidized form. 12) In the present study, we tentatively called the reversibly oxidized form HNA-1 and the irreversibly oxidized form HNA-2. Figure 1 shows the percentages (%) for (A) HMA and (B) HNA (HNA-1 and HNA-2) of 4 commercially available medical-grade HSA products and HSA obtained from human subjects (young and older groups, and patients receiving regular HD (pre-and post-HD)).…”

“…These markedly low thiol levels as well as high irreversible oxidation levels for medical-grade HSA products are in accordance with previous findings for various types of plasma-derived and recombinant HSA products in laboratory use obtained from Sigma Chem. Co. 11,12) Hayashi et al 20) demonstrated that the thiol-redox state of HSA isolated from the body was markedly influenced by the preservation temperature and/or period of sample storage. Medical-grade HSA solutions are produced in mass quantities by pharmaceutical industries.…”

“…4, a positive correlation was observed between carbonyl formation and thiol oxidation (r=0.840, p<0.001), however, the molecular mechanism responsible for oxidative modification markedly differed; for example, the specific target amino acid residues of proteins in carbonyl formation were Lys residues, 10) whereas that in thiol oxidation was the Cys residue. 9) Therefore, as in the case of thiol oxidative modification of isolated and recombinant HSA products for laboratory use, 11,12) significant amounts of carbonylated albumin in all medical-grade HSA products may be caused by long-time exposure to ROS during the manufacturing, isolation, and storage processes of plasma from human donors, even with special and careful treatments in the pharmaceutical industries. Anraku et al 25) also demonstrated that long-term (ca.10 h) exposure to a specific oxidative agent, 2,2′-azobis(2-amidino-propane) dihydrochloride (AAPH), resulted in a significant increase in the amount of carbonylated HSA obtained from human donors, even in the presence of albumin-specific stabilizers (N-Ac Trp and caprylate).…”

“…Co., St. Louis, MO, U.S.A.), such as plasma-derived and recombinant HSA products, for laboratory use. 11,12) In the present study, we investigated the quantitation of these particular PTMs in commercially available HSA solutions for clinical use in Japan, in comparison with those of healthy and diseased subjects. Furthermore, the effect of these PTMs on structural characteristics, such as thermal stability and secondary structure content, were determined using physicochemical techniques (differential scanning calorimetry (DSC) and circular dichroism (CD) spectropolarimetry).…”