The thiol of human serum albumin: Acidity, microenvironment and mechanistic insights on its oxidation to sulfenic acid

Bonanata, Jenner; Turell, Lucía; Antmann, Laura; Ferrer-Sueta, Gerardo; Botasini, Santiago; Méndez, Eduardo; Álvarez, Beatriz; Coitiño, Elena L.

doi:10.1016/j.freeradbiomed.2017.04.021

Cited by 45 publications

(34 citation statements)

References 69 publications

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“…Other studies, using different methodologies and other experimental conditions (buffers, temperature, etc.) found even lower values [27]. This discrepancy between experimental (pK a 8-9) and the computational values (pK a 11.0) may be explained by assuming that only in the crystal state the free carboxylate of Asp 38 is near enough to modify the acid-base property of Cys 34 .…”

Section: About the Reactivity Of Cys 34mentioning

confidence: 90%

Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys₃₄

et al. 2018

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Human serum albumin (HSA) is characterized by 17 disulfides and by only one unpaired cysteine (Cys ), which can be free in the reduced albumin or linked as a mixed disulfide with cysteine, or in minor amount with other natural thiols, in the oxidized albumin. In healthy subjects, the level of the oxidized form is about 35%, but it rises up to 70% after oxidative insults or in patients with kidney diseases. Oxidized albumin is therefore considered a short-term biomarker of oxidative stress as its level may increase or decrease under appropriate redox inputs in discrete temporal spans. This paper defines, for the first time, the kinetic properties of reduced and oxidized Cys of HSA in their reactions with natural disulfides and thiols. Kinetic constants support the evidence that the Cys redox oscillations observed in vivo are mainly due to the interaction with cysteine and cystine without the involvement of any enzymatic support. This study gives also a plausible explanation for the absence of involvement of the 17 disulfides naturally present in HSA in these redox transitions. This inert behavior toward cysteine is marginally due to solvent accessibility or flexibility factors of these bonds but mainly to their strong thermodynamic stability, which is caused essentially by a proximity effect. A similar mechanism is likely at play in the many proteins that maintain disulfide bridges in a reducing medium like the cytosol.

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Section: About the Reactivity Of Cys 34mentioning

confidence: 90%

Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys₃₄

et al. 2018

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“…The change in the shape of the spectrum in this region (peaks g , g’ and i ) is highly likely associated with a change in the conformation of Tyr84 and its microenvironment. According to abundant evidence, Tyr84 plays a key role in the reactivity of Cys34 [ 133 , 134 ]. Additionally, we suppose that peak f in oxidised BSA could be a signal of the benzene ring of EtAc covalently bound to the SH-group of Cys34 [ 135 ].…”

Section: Interplay Of Binding Enzymatic and Antioxidant Propertiementioning

confidence: 99%

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

et al. 2020

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As a carrier of many biologically active compounds, blood is exposed to oxidants to a greater extent than the intracellular environment. Serum albumin plays a key role in antioxidant defence under both normal and oxidative stress conditions. This review evaluates data published in the literature and from our own research on the mechanisms of the enzymatic and non-enzymatic activities of albumin that determine its participation in redox modulation of plasma and intercellular fluid. For the first time, the results of numerous clinical, biochemical, spectroscopic and computational experiments devoted to the study of allosteric modulation of the functional properties of the protein associated with its participation in antioxidant defence are analysed. It has been concluded that it is fundamentally possible to regulate the antioxidant properties of albumin with various ligands, and the binding and/or enzymatic features of the protein by changing its redox status. The perspectives for using the antioxidant properties of albumin in practice are discussed.

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“…In fact, in blood as well as in extravascular fluids, albumin is susceptible to different oxidative modifications, especially thiol oxidation and carbonylation [66,67]. Although albumin circulates primarily in its reduced form, about 30-40% of its reactive Cys 34 residues could be variably oxidized, either reversibly as mixed disulphide with low-molecular-weight thiols [68], S-nitroso Cys [69], or sulfenic acid [70] or irreversibly as sulfinic or sulfonic acid [52] (Figure 1). Furthermore, it has been described that albumin, through its nucleophilic Cys 34 residue, acts as scavenger for proatherogenic species such as 4-hydroxytrans-2-nonenal [71].…”

Section: Human Serum Albumin As a Carrier Of Harmful Lmw Thiols Insidmentioning

confidence: 99%

Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

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2020

Oxidative Medicine and Cellular Longevity

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Although oxidative stress has been long associated with the genesis and progression of the atherosclerotic plaque, scanty data on its in situ effects on protein sulfhydryl group modifications are available. Within the arterial wall, protein sulfhydryls and low-molecular-weight (LMW) thiols are involved in the cell regulation of both Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) levels and are a target for several posttranslational oxidative modifications that take place inside the atherosclerotic plaque, probably contributing to both atherogenesis and atherosclerotic plaque progression towards complicated lesions. Advanced carotid plaques are characterized by very high intraplaque GSH levels, due to cell lysis during apoptotic and/or necrotic events, probably responsible for the altered equilibrium among protein sulfhydryls and LMW thiols. Some lines of evidence show that the prooxidant environment present in atherosclerotic tissue could modify filtered proteins also by protein-SH group oxidation, and demonstrate that particularly albumin, once filtered, represents a harmful source of homocysteine and cysteinylglycine inside the plaque. The oxidative modification of protein sulfhydryls, with particular emphasis to protein thiolation by LMW thiols and its association with atherosclerosis, is the main topic of this review.

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The thiol of human serum albumin: Acidity, microenvironment and mechanistic insights on its oxidation to sulfenic acid

Cited by 45 publications

References 69 publications

Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys₃₄

Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys₃₄

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

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The thiol of human serum albumin: Acidity, microenvironment and mechanistic insights on its oxidation to sulfenic acid

Cited by 45 publications

References 69 publications

Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys34

Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys34

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

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Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys₃₄

Thiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys₃₄