A metalloproteomic analysis of interactions between plasma proteins and zinc: elevated fatty acid levels affect zinc distribution

Coverdale, James P. C.; Barnett, James P.; Adamu, Adamu H.; Griffiths, Ellie J.; Stewart, Alan J.; Blindauer, Claudia A.

doi:10.1039/c9mt00177h

Cited by 34 publications

(58 citation statements)

References 122 publications

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“…Recent investigations by Coverdale et al [10] confirm and expand the knowledge on the impact of elevated concentrations of free fatty acids (FFAs) on the interactions between proteins, especially albumin and zinc. Physiologically relevant long-chain FFAs, for example, palmitate and stearate, have a higher affinity to albumin than zinc.…”

Section: Functions Of Zincmentioning

confidence: 88%

Zinc Deficiency—An Independent Risk Factor in the Pathogenesis of Haemorrhagic Stroke?

2020

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Zinc is an essential trace element for human health and plays a fundamental role in metabolic, immunological and many other biological processes. The effects of zinc are based on the intra- and extracellular regulatory function of the zinc ion (Zn2+) and its interactions with proteins. The regulation of cellular zinc homeostasis takes place via a complex network of metal transporters and buffering systems that react to changes in the availability of zinc in nutrition, chronic diseases, infections and many other processes. Zinc deficiency is associated with impairment of numerous metabolic processes, reduced resistance to infections due to impaired immune functions, changes in skin and its appendages and disorders of wound healing and haemostasis. While ischemic heart attacks (myocardial infarction) occur more frequently with meat-based normal diets, haemorrhagic strokes are more frequently observed with vegetarian/vegan diets. The causes are discussed as deficiencies of various micronutrients, such as vitamin B12, vitamin D, various amino acids and also zinc. In the present review, after a description of the functions of zinc and its resorption, a discussion of daily food intake will follow, with a special focus on the importance of food composition and preparation for the zinc balance. The close interrelationships between proteins, especially albumin and zinc will be discussed. Finally, the possible causes and consequences of a zinc deficiency on the blood vessels and blood coagulation are considered.

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Section: Functions Of Zincmentioning

confidence: 88%

Zinc Deficiency—An Independent Risk Factor in the Pathogenesis of Haemorrhagic Stroke?

2020

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“…Thus, when pathological concentrations of FFAs are present in the blood, such as is the case in T2DM and in some cases of T1DM, Zn 2+ handling/buffering by serum albumin is dysregulated and plasma zinc speciation (the molecules to which it is bound) is altered [86]. Recently we have shown using size-exclusion-chromatography-ICP-MS that Zn 2+ is redistributed among other plasma proteins in the presence of pathophysiological FFA concentrations [87]. Considering the many coagulatory proteins that are regulated by Zn 2+ , this altered zinc speciation can dysregulate coagulation, resulting in increased platelet aggregation, increased fibrin clot density, and delayed fibrinolysis, thus potentially participating in the elevated thrombotic risks found in T2DM [86].…”

Section: Changes In Metal Ion Homeostasismentioning

confidence: 99%

Coagulatory Defects in Type-1 and Type-2 Diabetes

Sobczak

Stewart

2019

IJMS

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Diabetes (both type-1 and type-2) affects millions of individuals worldwide. A major cause of death for individuals with diabetes is cardiovascular diseases, in part since both types of diabetes lead to physiological changes that affect haemostasis. Those changes include altered concentrations of coagulatory proteins, hyper-activation of platelets, changes in metal ion homeostasis, alterations in lipid metabolism (leading to lipotoxicity in the heart and atherosclerosis), the presence of pro-coagulatory microparticles and endothelial dysfunction. In this review, we explore the different mechanisms by which diabetes leads to an increased risk of developing coagulatory disorders and how this differs between type-1 and type-2 diabetes.

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“…Among the seven sites identified in HSA for medium‐ and long‐chain FAs (from C 10 to C 18 ) named FA1–FA7, FA2, FA4, and FA5 exhibit the highest affinity . The binding of FAs to the site FA2, located at the interface of the subdomains IA and IIA, causes their rotation, separating the coordinating amino acid of MBS, which becomes no longer available for Zn 2+ or, in general, for metal binding.…”

Section: Resultsmentioning

confidence: 99%

“…The relationship between the binding of fatty acids (FAs) and some metal ions was suggested: it is proved that Zn 2+ coordination to the MBS can be hindered by the binding of FAs at their strongest site, FA2, causing a rotation of the subdomains where the MBS is located and separating the zinc amino acid donors. Such conformational changes can influence the binding of other metal ions and, therefore, the transport properties of albumin.…”

Section: Introductionmentioning

confidence: 99%

Unveiling V^IVO²⁺ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

Sciortino

Sanna

Lubinu

et al. 2020

Chemistry A European J

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Human serum albumin (HSA) is involved in the transport of metal ions and potential metallodrugs. Depending on the metal, several sites are available, among which are N‐terminal (NTS) and multi‐metal binding sites (MBS). Despite the large number of X‐ray determinations for albumins, only one structure with Zn2+ is available. In this work, the binding to HSA of the VIVO2+ ion was studied by an integrated approach based on spectroscopic and computational methods, which allowed the systems to be characterized even in the absence of X‐ray analysis. The behavior depends on the type of albumin, defatted (HSAd) or fatted (HSAf). With HSAd ‘primary’ and ‘secondary’ sites were revealed, NTS with (His3, His9, Asp13, Asp255) and MBS with (His67, His247, Asp249, Asn99 or H2O); with increasing the ratio VIVO2+/HSAd, ‘tertiary’ sites, with one His‐N and other donors (Asp/Glu‐O or carbonyl‐O) are populated. With HSAf, fatty acids (FAs) cause a rotation of the subdomains IA and IIA, which results in the formation of a dinuclear ferromagnetic adduct (VIVO)2D(HSAf) with a μ1,1‐Asp249 and the binding of His247, Glu100, Glu252, and His67 or Asn99. FAs hinder also the binding of VIVO2+ to the MBS.

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A metalloproteomic analysis of interactions between plasma proteins and zinc: elevated fatty acid levels affect zinc distribution

Abstract: Serum albumin is the major zinc carrier in blood plasma. Fatty acid binding to albumin regulates its zinc-binding ability and alters plasma zinc speciation.

Cited by 34 publications

References 122 publications

Zinc Deficiency—An Independent Risk Factor in the Pathogenesis of Haemorrhagic Stroke?

Zinc Deficiency—An Independent Risk Factor in the Pathogenesis of Haemorrhagic Stroke?

Coagulatory Defects in Type-1 and Type-2 Diabetes

Unveiling V^IVO²⁺ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

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A metalloproteomic analysis of interactions between plasma proteins and zinc: elevated fatty acid levels affect zinc distribution

Abstract: Serum albumin is the major zinc carrier in blood plasma. Fatty acid binding to albumin regulates its zinc-binding ability and alters plasma zinc speciation.

Cited by 34 publications

References 122 publications

Zinc Deficiency—An Independent Risk Factor in the Pathogenesis of Haemorrhagic Stroke?

Zinc Deficiency—An Independent Risk Factor in the Pathogenesis of Haemorrhagic Stroke?

Coagulatory Defects in Type-1 and Type-2 Diabetes

Unveiling VIVO2+ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach

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Unveiling V^IVO²⁺ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach