Preservation of Structure and Function During Isolation of Human Plasma Proteins

Plasma proteins are covalently modified in vivo by the high-glucose conditions in the bloodstreams of people with diabetes, resulting in changes to both structure and function.

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Zinc: An important cofactor in haemostasis and thrombosis

Thrombosis and Haemostasis ◽

10.1160/th12-07-0465 ◽

2013 ◽

Vol 109 (03) ◽

pp. 421-430 ◽

Cited By ~ 36

Author(s):

Trang Vu ◽

James Fredenburgh ◽

Jeffrey Weitz

Keyword(s):

Platelet Aggregation ◽

Transition Metal ◽

Zinc Deficiency ◽

Plasma Proteins ◽

Structure And Function ◽

Important Mediator ◽

Activated Platelets ◽

And Function

SummaryThere is mounting evidence that zinc, the second most abundant transition metal in blood, is an important mediator of haemostasis and thrombosis. Prompted by the observation that zinc deficiency is associated with bleeding and clotting abnormalities, there now is evidence that zinc serves as an effector of coagulation, anticoagulation and fibrinolysis. Zinc binds numerous plasma proteins and modulates their structure and function. Because activated platelets secrete zinc into the local microenvironment, the concentration of zinc increases in the vicinity of a thrombus. Consequently, the role of zinc varies depending on the microenvironment; a feature that endows zinc with the capacity to spatially and temporally regulate haemostasis and thrombosis. This paper reviews the mechanisms by which zinc regulates coagulation, platelet aggregation, anticoagulation and fibrinolysis and outlines how zinc serves as a ubiquitous modulator of haemostasis and thrombosis.

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Structure and function of plasma Proteins, Volume 2

Trends in Biochemical Sciences ◽

10.1016/0968-0004(77)90372-3 ◽

1977 ◽

Vol 2 (7) ◽

pp. 166-167

Author(s):

Hugh Gordon

Keyword(s):

Plasma Proteins ◽

Structure And Function ◽

And Function

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Global chemical modifications comparison of human plasma proteomes from two different age groups

10.1101/2020.03.07.978049 ◽

2020 ◽

Author(s):

Yongtao Liu ◽

Mindi Zhao ◽

Xuanzhen Pan ◽

Youhe Gao

Keyword(s):

Amino Acid ◽

Human Plasma ◽

Age Groups ◽

Young Group ◽

Structure And Function ◽

Plasma Proteome ◽

Chemical Modifications ◽

Old People ◽

And Function ◽

Human Plasma Proteome

AbstractThe chemical modification of proteins refers to the covalent group reaction involved in their amino acid residues or chain ends which, in turn, change the molecular structure and function of the proteins. There are many types of molecular modifications in the human plasma proteome, such as phosphorylation, methylation, and acetylation. In this study, two groups of human plasma proteome at different age groups (old and young) were used to perform a comparison of global chemical modifications, as determined by tandem mass spectrometry (MS/MS) combined with non-limiting modification identification algorithms. The sulfhydryl in the cysteine A total of 4 molecular modifications were found to have significant differences: the succinylation and phosphorylation modification of cysteine (Cys, C) and the modification of lysine (Lys, K) with threonine (Thr, T) were significantly higher in the old group than in the young group, while the carbamylation of lysine was lower in the young group. Cysteine residue is an important group for forming disulphide bonds and maintaining the structure of the protein. Differential cysteine-related sulfydryl modifications may cause structural and functional changes. Lysine is a basic amino acid, and the modification of its amino group will change the charge state of the protein, which may affect the structure and function of the protein. In summary, four types of protein chemical modifications and substitutes were found to be significantly different in the plasma proteome in different age groups and their probabilities of random generation are lower by passing random grouping test. We speculate that there is an increase in certain modified proteins in the blood of the old people which, in turn, changes the function of those proteins. This change may be one of the reasons why the old people are more likely than the young people to be at risk for age-related diseases, such as metabolic diseases, cerebral and cardiovascular diseases, and cancer.

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Structure and Function of the Human Plasma Apolipoproteins

Atherosclerosis V ◽

10.1007/978-1-4612-6071-4_122 ◽

1980 ◽

pp. 624-630 ◽

Cited By ~ 1

Author(s):

Henry J. Pownall ◽

James T. Sparrow ◽

Louis C. Smith ◽

Antonio M. Gotto

Keyword(s):

Human Plasma ◽

Structure And Function ◽

And Function

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Mechanism for the homocysteine-enhanced antifibrinolytic potential of lipoprotein(a) in human plasma

Thrombosis and Haemostasis ◽

10.1160/th04-12-0808 ◽

2005 ◽

Vol 94 (07) ◽

pp. 75-81 ◽

Cited By ~ 3

Author(s):

Marina Nardulli ◽

Vincent Durlach ◽

Gabriella Pepe ◽

Eduardo Anglés-Cano

Keyword(s):

Human Plasma ◽

Structure And Function ◽

Plasma Homocysteine ◽

Plasminogen Activation ◽

Total Plasma ◽

Lipoprotein A ◽

High Affinity ◽

Main Target ◽

And Function ◽

Acting In Concert

SummaryLipoprotein(a) and total plasma homocysteine levels are now established as independent atherothrombogenic risk factors. A distinctive pathophysiological feature of lipoprotein(a) is its antifibrinolytic activity, an effect dependent on plasma concentration and high affinity for fibrin of its small size apo(a) component. A stimulating effect of homocysteine on purified lipoprotein(a) has been proposed. However, little is known about their specific interactions in human plasma. We demonstrate by immunochemical, ligand-binding and plasminogen activation studies, that homocysteine modifies the structure and function of lipoprotein(a) in human plasma; it reduces the apo(a)/apoB disulfide bond causing the appearance of free apo(a) with high affinity for fibrin that inhibits plasminogen binding and plasmin formation (r= −0.995, p=0.002). These effects were evident particularly in plasma samples containing lipoprotein(a) with low affinity for fibrin and more than 22 kringles apo(a) isoforms. In contrast, for plasmas containing high fibrin affinity lipoprotein(a) (less than 22 kringles apo[a] isoforms) no significant change neither in fibrin binding nor in plasmin formation was observed. Furthermore, isolated apo(a) recombinants (10 to 34 kringles) that have been shown to display size-independent high affinity for fibrin were not affected by homocysteine, thus confirming lipoprotein(a) as its main target. These results suggest that the pro-atherogenic role already conferred to lipoprotein(a) by small apo(a) isoforms may be extended to large apo(a) isoforms if released in plasma by homocysteine, as this mechanism reveals their high fibrin affinity. Lipoprotein(a) and homocysteine may therefore constitute, if acting in concert, a new risk factor for athero-thrombotic vascular disease.

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