The thiol pool in human plasma: the central contribution of albumin to redox processes.
TL;DR: A critical review of the plasma thiol pool is provided with a focus on human serum albumin, an important target for oxidants and electrophiles due to its reactivity with a wide variety of species and its relatively high concentration.
About: This article is published in Free Radical Biology and Medicine.The article was published on 2013-12-01 and is currently open access. It has received 519 citations till now. The article focuses on the topics: Human serum albumin & Thiol.
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TL;DR: In this paper, the authors developed a novel and automated assay determining plasma thiol/disulphide homeostasis, which consists of thiol-disoulphide exchanges.
658 citations
TL;DR: A key conclusion is a reinforcement of the concept that NAC should not be considered to be a powerful antioxidant in its own right: its strength is the targeted replenishment of GSH in deficient cells and it is likely to be ineffective in cells replete in GSH.
481 citations
Cites background from "The thiol pool in human plasma: the..."
...(Turell et al., 2013) and there are few data available to indicate whether intravenous NAC can influence plasma total antioxidant capacity....
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...The thiol pool and antioxidant potential is therefore dominated by albumin (Turell et al., 2013) and there are few data available to indicate whether intravenous NAC can influence plasma total antioxidant capacity....
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TL;DR: The disulphide breaking activity of NAC also explains its mucolytic activity which is due to its effect in reducing heavily cross-linked mucus glycoproteins and free thiols as well as reduced proteins which have important direct antioxidant activity.
Abstract: The main molecular mechanisms explaining the well-established antioxidant and reducing activity of N-acetylcysteine (NAC), the N-acetyl derivative of the natural amino acid l-cysteine, are summarised and critically reviewed. The antioxidant effect is due to the ability of NAC to act as a reduced glutathione (GSH) precursor; GSH is a well-known direct antioxidant and a substrate of several antioxidant enzymes. Moreover, in some conditions where a significant depletion of endogenous Cys and GSH occurs, NAC can act as a direct antioxidant for some oxidant species such as NO2 and HOX. The antioxidant activity of NAC could also be due to its effect in breaking thiolated proteins, thus releasing free thiols as well as reduced proteins, which in some cases, such as for mercaptoalbumin, have important direct antioxidant activity. As well as being involved in the antioxidant mechanism, the disulphide breaking activity of NAC also explains its mucolytic activity which is due to its effect in reducing heavily cross-linked mucus glycoproteins. Chemical features explaining the efficient disulphide breaking activity of NAC are also explained.
421 citations
TL;DR: A comprehensive overview of the key sequences and structures utilised to provide biological and physical stability to nano-constructs, direct particles to their target and influence their cellular and tissue distribution, induce and control biological responses, and form polypeptide self-assembled nanoparticles are provided.
Abstract: Peptide- and protein-nanoparticle conjugates have emerged as powerful tools for biomedical applications, enabling the treatment, diagnosis, and prevention of disease. In this review, we focus on the key roles played by peptides and proteins in improving, controlling, and defining the performance of nanotechnologies. Within this framework, we provide a comprehensive overview of the key sequences and structures utilised to provide biological and physical stability to nano-constructs, direct particles to their target and influence their cellular and tissue distribution, induce and control biological responses, and form polypeptide self-assembled nanoparticles. In doing so, we highlight the great advances made by the field, as well as the challenges still faced in achieving the clinical translation of peptide- and protein-functionalised nano-drug delivery vehicles, imaging species, and active therapeutics.
315 citations
Cites background from "The thiol pool in human plasma: the..."
...thiols in the blood is far lower than that observed intracellularly, it remains high enough to induce loss of monothiol coatings during circulation.(116) This is in part due to the possibility for dissociative ligand exchange (SN1-like pathway), in which ligands are rapidly diluted within serum upon dissociation, and replaced by circulating small molecule thiols....
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TL;DR: This work introduces a novel integrative concept defined as the reactive species interactome (RSI), a primeval multilevel redox regulatory system whose architecture allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level.
Abstract: Significance: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constitu...
224 citations
Cites background from "The thiol pool in human plasma: the..."
...Both within cells (75) and in blood (195), proteins constitute by far the largest pool of redox-active thiols....
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...Nevertheless, albumin is likely to play a more important role quantitatively simply based on its abundance in the extracellular compartment (195) and the extent to which it transports small aminothiols....
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...Approximately 60% of the total thiol groups in serum/plasma are accounted for by the single free cysteine (Cys(34)) of albumin (195)....
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References
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TL;DR: The data support the idea of a "beneficial" role for bilirubin as a physiological, chain-breaking antioxidant.
Abstract: Bilirubin, the end product of heme catabolism in mammals, is generally regarded as a potentially cytotoxic, lipid-soluble waste product that needs to be excreted. However, it is here that bilirubin, at micromolar concentrations in vitro, efficiently scavenges peroxyl radicals generated chemically in either homogeneous solution or multilamellar liposomes. The antioxidant activity of bilirubin increases as the experimental concentration of oxygen is decreased from 20% (that of normal air) to 2% (physiologically relevant concentration). Furthermore, under 2% oxygen, in liposomes, bilirubin suppresses the oxidation more than alpha-tocopherol, which is regarded as the best antioxidant of lipid peroxidation. The data support the idea of a "beneficial" role for bilirubin as a physiological, chain-breaking antioxidant.
3,299 citations
Book•
22 Dec 1995
TL;DR: The Albumin Molecule: Its Structure and Chemical Properties and Practical Aspects: Albumin in the Laboratory.
Abstract: A Historical Perspective. The Albumin Molecule: Its Structure and Chemical Properties. Ligand Binding by Albumin. Genetics: The Albumin Gene. Metabolism: Albumin in the Body. Clinical Aspects: Albumin in Medicine. Practical Aspects: Albumin in the Laboratory. Subject Index.
2,672 citations
TL;DR: Peroxynitrite anion was a less effective thiol-oxidizing agent than its anion, with oxidation presumably mediated by the decomposition products, hydroxyl radical and nitrogen dioxide.
2,487 citations
TL;DR: In this article, an elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism.
Abstract: An elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism. The basis for these conclusions is data from about 80 clinical and epidemiological studies including more than 10,000 patients. Elevated tHcy confers a graded risk with no threshold, is independent of but may enhance the effect of the conventional risk factors, and seems to be a particularly strong predictor of cardiovascular mortality. Hyperhomocysteinemia is attributed to commonly occurring genetic and acquired factors including deficiencies of folate and vitamin B12. Supplementation with B-vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce an elevated tHcy level. Studies are now in progress to establish whether such therapy will reduce cardiovascular risk.
2,099 citations
"The thiol pool in human plasma: the..." refers background in this paper
...Regarding the plasma thiol pool, homocysteine deserves special mention because increased concentrations are associated with cardiovascular disease and neural tube defects [10,11]....
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TL;DR: This review gives an account of the different drug delivery systems which make use of albumin as a drug carrier with a focus on those systems that have reached an advanced stage of preclinical evaluation or that have entered clinical trials.
1,913 citations