Relative Roles of Albumin and Ceruloplasmin in the Formation of Homocystine, Homocysteine-Cysteine-mixed Disulfide, and Cystine in Circulation

Sengupta, Shantanu; Wehbe, Charles; Majors, Alana K.; Ketterer, Michael E.; DiBello, Patricia M.; Jacobsen, Donald W.

doi:10.1074/jbc.m108451200

Cited by 122 publications

(98 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although increased protein S-thiolation is considered an in vivo marker of oxidative injury caused by noxious agents (21,22 ), the importance of this index in clinical studies has not been well documented. Thiols in plasma are mainly linked to albumin, but interactions between Hcy and ceruloplasmin, fibrin, and transthyretin have also been reported (23)(24)(25). These Hcy-mediated posttranslational modifications may have important functional consequences.…”

Section: Discussionmentioning

confidence: 99%

Factors Affecting S-Homocysteinylation of LDL Apoprotein B

Zinellu

Sotgia

et al. 2006

Clinical Chemistry

View full text Add to dashboard Cite

Background: Hyperhomocysteinemia is an important risk factor for vascular disease and atherosclerosis, but the mechanisms by which homocysteine exerts its deleterious effects are not known. Because oxidation and/or homocysteinylation may increase atherogenicity of LDL, we investigated S-homocysteinylation of LDL as a possible contributor to atherosclerosis pathogenesis. Methods: We used capillary electrophoresis to measure LDL-bound thiols [homocysteine, cysteine (Cys), cysteinylglycine, glutathione, and glutamylcysteine] in 104 healthy study participants We also assessed total plasma thiol concentrations and lipid profiles. Results: Our data suggest that apoprotein B (apoB)-cysteinylglycine (CysGly), apoB-Hcy, and apoB-Cys concentrations are markedly higher in men than in women. The percentage of CysGly and glutathione on apoB was higher than that of the same thiols in plasma, whereas the other thiols were markedly less prevalent in lipoprotein than in plasma. Pearson correlation showed that among all thiols, only total plasma Hcy is related to apoB-Hcy concentrations. Multiple correlation analysis confirmed that total Hcy was the most important determinant of apoB-Hcy. Age and LDL cholesterol also showed positive associations, but Cys and, mainly, CysGly were negatively associated with apoB-Hcy concentrations. Conclusions: apoB-Hcy derivative formation is mainly dependent on total homocysteine concentration. Increased cholesterol concentrations are related to increased apoB-Hcy. CysGly seems to compete with Hcy for binding to LDL apoprotein, suggesting that CysGly

show abstract

Section: Discussionmentioning

confidence: 99%

Factors Affecting S-Homocysteinylation of LDL Apoprotein B

Zinellu

Sotgia

et al. 2006

Clinical Chemistry

View full text Add to dashboard Cite

show abstract

“…Thiol groups on the surface of albumin are oxidized by oxidants (Sengupta et al 2001). Thus, low level of albumin can cause oxidative stress (Sengupta et al 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Thiol groups on the surface of albumin are oxidized by oxidants (Sengupta et al 2001). Thus, low level of albumin can cause oxidative stress (Sengupta et al 2001). Uric acid is another wellknown low molecular weight water-soluble plasma antioxidant (Erel 2004).…”

Section: Discussionmentioning

confidence: 99%

Decreased Total Antioxidant Response and Increased Oxidative Stress in Behcet's Disease

Işık

Koca

Üstündağ

et al. 2007

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Behcet's disease (BD) is a chronic systemic inflammatory disease. Inflammatory reactions trigger the oxidative stress and oxidants decrease the level of antioxidants. In the present study, we aimed to determine serum oxidative/antioxidative status in patients with BD. Serum antioxidative status was evaluated by measuring total antioxidant capacity (TAC), paraoxonase 1, arylesterase, sulfhydryl groups and ceruloplasmin in patients with BD and in healthy controls. Serum oxidative status was evaluated by measuring total peroxide (TP), lipid hydroperoxides and oxidative stress index (OSI). OSI was calculated by percent ratio of TP to TAC. Serum levels of TAC, sulfhydryl groups and activities of paraoxonase 1, arylesterase, and ceruloplasmin were significantly lower in patients than in controls ( p < 0.001 for all). In contrast, TP, lipid hydroperoxides and OSI values were significantly higher in patients than in controls ( p < 0.001 for all). Further, the level of TAC was negatively correlated with the levels of TP, lipid hydroperoxides and OSI both in the BD (r = −0.578, p < 0.01; r = −0.559, p < 0.01 and r = −0.552, p < 0.01, respectively) and the control groups (r = −0.469, p < 0.05; r = −0.351, p < 0.05 and r = −0.391, p < 0.05, respectively). These results indicate that the oxidant parameters increased and antioxidant parameters decreased in patients with BD; therefore, these patients might have been exposed to oxidative stress. We suggest that impaired oxidant/ antioxidant balance should be taken into consideration in the follow-up of patients with BD.

show abstract

“…In healthy well-nourished individuals, homocysteine metabolism is efficient and regulated, and the concentration of plasma total homocysteine is usually Յ12 mol/L. 1 Inborn errors of homocysteine metabolism, drugs that interfere with homocysteine metabolism, deficiencies of folic acid, vitamin B 6 or vitamin B 12 , and certain disease states, such as chronic renal failure, increase plasma total homocysteine levels. 2 The homocystinurias are a heterogeneous group of autosomal recessive diseases caused by inborn errors of homocysteine metabolism.…”

mentioning

confidence: 99%

Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin

Majors

Sengupta

Willard

et al. 2002

ATVB

Self Cite

View full text Add to dashboard Cite

Objective-More than 70% of circulating homocysteine is disulfide-bonded to protein, but little is known about the specific proteins that bind homocysteine and their function as a consequence of homocysteine binding. Methods and Results-When human plasma was incubated with [35 S]L-homocysteine, most of the homocysteine bound to albumin. However, additional homocysteine-binding proteins were detected, and 1 of them comigrated with fibronectin. Treatment with 2-mercaptoethanol removed the bound homocysteine, demonstrating the involvement of disulfide bonding. In contrast, [35 S]L-cysteine did not bind to fibronectin. Purified fibronectin bound Ϸ5 homocysteine molecules per fibronectin dimer. SDS-PAGE of a limited trypsin digestion of homocysteinylated fibronectin showed that several tryptic fragments contained [35 S]homocysteine. Sequence analysis demonstrated that the fragments containing bound homocysteine had localized mainly to the C-terminal region, within and adjacent to the fibrin-binding domain. Homocysteinylation of fibronectin significantly inhibited its capacity to bind fibrin by 62% (PϽ0.005). In contrast, neither the binding of fibronectin to gelatin nor its capacity to serve as an attachment factor for aortic smooth muscle cells was affected. Key Words: homocysteine Ⅲ fibronectin Ⅲ fibrin Ⅲ atherosclerosis Ⅲ thrombosis H omocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. In healthy well-nourished individuals, homocysteine metabolism is efficient and regulated, and the concentration of plasma total homocysteine is usually Յ12 mol/L. 1 Inborn errors of homocysteine metabolism, drugs that interfere with homocysteine metabolism, deficiencies of folic acid, vitamin B 6 or vitamin B 12 , and certain disease states, such as chronic renal failure, increase plasma total homocysteine levels. 2 The homocystinurias are a heterogeneous group of autosomal recessive diseases caused by inborn errors of homocysteine metabolism. [3][4][5] Patients with untreated homocystinuria have severe hyperhomocysteinemia (50 to 500 mol/L) and lifethreatening premature cardiovascular disease. Thrombosis, with or without embolism, is the major cause of death. Postmortem studies show multiple thrombotic occlusions and widespread premature atherosclerosis with intimal thickening. However, even mild hyperhomocysteinemia (15 to 25 mol/L), regardless of the underlying cause, is a strong independent risk factor for occlusive vascular disease, as shown by numerous case-control and prospective studies involving thousands of subjects. 1,2,6 The mechanisms of homocysteine-induced atherosclerosis and thrombosis have not been fully elucidated. Conclusions-TheseIn normal individuals, Ͼ70% of circulating homocysteine is disulfide-bonded to plasma proteins. 7,8 The primary carrier of disulfide-bound homocysteine is albumin, 9 -12 but other proteins with accessible cysteine residues are also potential carriers. The binding of homocysteine to cysteine residues may disrupt normal protein structure and impair...

show abstract

Relative Roles of Albumin and Ceruloplasmin in the Formation of Homocystine, Homocysteine-Cysteine-mixed Disulfide, and Cystine in Circulation

Cited by 122 publications

References 52 publications

Factors Affecting S-Homocysteinylation of LDL Apoprotein B

Factors Affecting S-Homocysteinylation of LDL Apoprotein B

Decreased Total Antioxidant Response and Increased Oxidative Stress in Behcet's Disease

Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin

Contact Info

Product

Resources

About