Mechanisms for the Formation of Protein-Bound Homocysteine in Human Plasma

Togawa, Tadayasu; Sengupta, Shantanu; Chen, Hong; Robinson, Killian; Nonevski, Ilche T.; Majors, Alana K.; Jacobsen, Donald W.

doi:10.1006/bbrc.2000.3723

Cited by 38 publications

(35 citation statements)

References 38 publications

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“…Binding of Hcys to plasma proteins is biphasic. First reaction, involving displacement of cysteine from plasma proteins, is rapid and oxygen independent, while the second reaction constitutes slower, oxygen-dependent thiol oxidation (Togawa et al 2000). Our present results showed that not only the reduced form of Hcys, but also its cyclic thioester may diminish the amount of free protein thiol concentration, especially when blood plasma is exposed for a long incubation time (60 min) (Fig.…”

supporting

confidence: 48%

May modifications of human plasma proteins stimulated by homocysteine and its thiolactone induce changes of hemostatic function of plasma in vitro?

Olas¹,

Kołodziejczyk²,

Malinowska³

2010

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Abstract. Homocysteine (Hcys) may be implicated in different diseases, especially in cardiovascular illnesses. The most reactive form of Hcys is its cyclic thioester -homocysteine thiolactone (HTL), which is formed in plasma and represents up to 0.29% of plasma total Hcys. Recently, it has been observed that Hcys and HTL may modify plasma proteins, including albumin, hemoglobin or fibrinogen, but the role of this process is not yet well known. The aim of our study in vitro was to investigate the modifications of human plasma total proteins after incubation with the reduced form of Hcys in concentrations 10-100 µmol/l, and HTL in concentrations 1-0.1 µmol/l, which correspond to levels found in human plasma during hyperhomocysteinemia in vivo. The aim of our study was also to explain the effects of Hcys and HTL on coagulation activity of human plasma. We showed that in model system in vitro Hcys and HTL change the level of thiol, amino and carbonyl groups in plasma total proteins. Moreover, our studies reported that not only Hcys (10-100 µmol/l), but also HTL (at lower concentrations than Hcys) modulates the coagulation properties of human plasma.

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supporting

confidence: 48%

May modifications of human plasma proteins stimulated by homocysteine and its thiolactone induce changes of hemostatic function of plasma in vitro?

Olas¹,

Kołodziejczyk²,

Malinowska³

2010

gpb

View full text Add to dashboard Cite

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“…The filtrate was then applied to an analytical Vydac C-4 HPLC column (25 ϫ 0.46 cm, 5-m particle size) and eluted at 0.75 ml/min over 30 min using a gradient of 40 -85% acetonitrile. Transthyretin and its Cys 10 conjugates eluted between 52 and 54% acetonitrile. The solvent mixture was removed from the protein using a Speedvac concentrator.…”

Section: Isolation and Purification Of Transthyretin Frommentioning

confidence: 99%

In Vitro and in Vivo Interactions of Homocysteine with Human Plasma Transthyretin

Lim

Sengupta

McComb

et al. 2003

Journal of Biological Chemistry

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Hyperhomocysteinemia is an independent risk factor for cardiovascular disease and an emerging risk factor for cognitive dysfunction and Alzheimer's disease. Greater than 70% of the homocysteine in plasma is disulfide-bonded to protein cysteine residues. The identity and functional consequences of protein homocysteinylation are just now emerging. The amyloidogenic protein transthyretin (prealbumin), as we now report, undergoes homocysteinylation at its single cysteine residue (Cys 10 ) both in vitro and in vivo. Thus, when human plasma or highly purified transthyretin was incubated with 35 S-L-homocysteine followed by SDS-PAGE and PhosphorImaging, two bands corresponding to transthyretin dimer and tetramer were observed. Treatment of the labeled samples with ␤-mercaptoethanol prior to SDS-PAGE removed the disulfide-bound homocysteine. Transthyretin-Cys 10 -S-S-homocysteine was then identified in vivo in plasma from normal donors, patients with end-stage renal disease, and homocystinurics by immunoprecipitation and high performance liquid chromatography/electrospray mass spectrometry. The ratios of transthyretin-Cys 10 -S-S-homocysteine and transthyretin-Cys 10 -S-S-sulfonate to that of unmodified transthyretin increased with increasing homocysteine plasma concentrations, whereas the ratio of transthyretin-Cys 10 -S-S-cysteine to that of unmodified transthyretin decreased. The hyperhomocysteinemic burden is thus reflected in the plasma levels of transthyretin-Cys 10

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“…Plasma-We recently determined the equilibrium binding capacity of plasma proteins for homocysteine but did not identify the specific proteins responsible for the binding (14). To identify specific homocysteine-binding proteins, human plasma was incubated with 35 S-L-homocysteine.…”

Section: Identification Of Albumin As a Binding Protein For Homocystementioning

confidence: 99%

“…However, in patients with homocystinuria, tHcy levels approach 0.5 mM (13). The overall in vitro binding capacity of human plasma proteins for homocysteine is Ͼ0.4 mM (14). Almost all pathophysiology studies utilize free reduced homocysteine (reviewed in Ref.…”

mentioning

confidence: 99%

Albumin Thiolate Anion Is an Intermediate in the Formation of Albumin-S–S-Homocysteine

Sengupta¹,

Chen²,

Togawa³

et al. 2001

Journal of Biological Chemistry

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158

173

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Mechanisms for the Formation of Protein-Bound Homocysteine in Human Plasma

Cited by 38 publications

References 38 publications

May modifications of human plasma proteins stimulated by homocysteine and its thiolactone induce changes of hemostatic function of plasma in vitro?

May modifications of human plasma proteins stimulated by homocysteine and its thiolactone induce changes of hemostatic function of plasma in vitro?

In Vitro and in Vivo Interactions of Homocysteine with Human Plasma Transthyretin

Albumin Thiolate Anion Is an Intermediate in the Formation of Albumin-S–S-Homocysteine

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