Homocysteine metabolism in peripheral blood mononuclear cells: Evidence for cystathionine beta-synthase activity in resting state

Monika Katko, Erzsebet Zavaczki, V. Jeney, G. Paragh, J. Balla, Z. Varga

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Activated peripheral blood mononuclear cells (PBMC) release homocysteine and possess cystathionine β-synthase (CBS) activity; however, it was thought that there is no CBS in resting state. Previously, we found that nickel decreased intracellular homocysteine concentration in un-stimulated (e.g. resting) PBMC, suggesting that resting PBMC might also have active homocysteine metabolism. Here, we demonstrated that un-stimulated PBMC synthesize (incorporate l-[methyl-14C]methionine to DNA, lipids and proteins), release (increase extracellular homocysteine), and metabolize homocysteine. Intracellular homocysteine concentration varied with incubation time, depending on extracellular concentrations of methionine, homocysteine, and glutathione. Methionine synthase activity was constant and independent of thiol concentrations. In Western blot, CBS protein was clearly identified in freshly isolated PBMC. CBS protein level and activity increased with incubation time, upon stimulation, and similar to intracellular homocysteine, depending on intra- and extracellular homocysteine and glutathione concentrations. According to our knowledge, this is the first evidence that certifies homocysteine metabolism and regulatory role of CBS activity to keep balanced intracellular homocysteine level in resting PBMC. Homocysteine, released by PBMC, in turn can modulate its functions contributing to the development of hyperhomocysteinemia-induced diseases.

Original languageEnglish
Pages (from-to)317-326
Number of pages10
JournalAmino Acids
Volume43
Issue number1
DOIs
Publication statusPublished - Jul 2012

Fingerprint

Cystathionine beta-Synthase
Homocysteine
Metabolism
Blood Cells
Blood
Methionine
Glutathione
Cystathionine
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
Hyperhomocysteinemia
Proteins
Nickel
Sulfhydryl Compounds

Keywords

  • Cystathionine β-synthase
  • Extracellular homocysteine
  • Glutathione
  • Intracellular homocysteine
  • Methionine
  • PBMC

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Homocysteine metabolism in peripheral blood mononuclear cells : Evidence for cystathionine beta-synthase activity in resting state. / Katko, Monika; Zavaczki, Erzsebet; Jeney, V.; Paragh, G.; Balla, J.; Varga, Z.

In: Amino Acids, Vol. 43, No. 1, 07.2012, p. 317-326.

Research output: Contribution to journalArticle

@article{0e6a109fb53c4349ae7d80ac6019d70d,
title = "Homocysteine metabolism in peripheral blood mononuclear cells: Evidence for cystathionine beta-synthase activity in resting state",
abstract = "Activated peripheral blood mononuclear cells (PBMC) release homocysteine and possess cystathionine β-synthase (CBS) activity; however, it was thought that there is no CBS in resting state. Previously, we found that nickel decreased intracellular homocysteine concentration in un-stimulated (e.g. resting) PBMC, suggesting that resting PBMC might also have active homocysteine metabolism. Here, we demonstrated that un-stimulated PBMC synthesize (incorporate l-[methyl-14C]methionine to DNA, lipids and proteins), release (increase extracellular homocysteine), and metabolize homocysteine. Intracellular homocysteine concentration varied with incubation time, depending on extracellular concentrations of methionine, homocysteine, and glutathione. Methionine synthase activity was constant and independent of thiol concentrations. In Western blot, CBS protein was clearly identified in freshly isolated PBMC. CBS protein level and activity increased with incubation time, upon stimulation, and similar to intracellular homocysteine, depending on intra- and extracellular homocysteine and glutathione concentrations. According to our knowledge, this is the first evidence that certifies homocysteine metabolism and regulatory role of CBS activity to keep balanced intracellular homocysteine level in resting PBMC. Homocysteine, released by PBMC, in turn can modulate its functions contributing to the development of hyperhomocysteinemia-induced diseases.",
keywords = "Cystathionine β-synthase, Extracellular homocysteine, Glutathione, Intracellular homocysteine, Methionine, PBMC",
author = "Monika Katko and Erzsebet Zavaczki and V. Jeney and G. Paragh and J. Balla and Z. Varga",
year = "2012",
month = "7",
doi = "10.1007/s00726-011-1080-2",
language = "English",
volume = "43",
pages = "317--326",
journal = "Amino Acids",
issn = "0939-4451",
publisher = "Springer Wien",
number = "1",

}

TY - JOUR

T1 - Homocysteine metabolism in peripheral blood mononuclear cells

T2 - Evidence for cystathionine beta-synthase activity in resting state

AU - Katko, Monika

AU - Zavaczki, Erzsebet

AU - Jeney, V.

AU - Paragh, G.

AU - Balla, J.

AU - Varga, Z.

PY - 2012/7

Y1 - 2012/7

N2 - Activated peripheral blood mononuclear cells (PBMC) release homocysteine and possess cystathionine β-synthase (CBS) activity; however, it was thought that there is no CBS in resting state. Previously, we found that nickel decreased intracellular homocysteine concentration in un-stimulated (e.g. resting) PBMC, suggesting that resting PBMC might also have active homocysteine metabolism. Here, we demonstrated that un-stimulated PBMC synthesize (incorporate l-[methyl-14C]methionine to DNA, lipids and proteins), release (increase extracellular homocysteine), and metabolize homocysteine. Intracellular homocysteine concentration varied with incubation time, depending on extracellular concentrations of methionine, homocysteine, and glutathione. Methionine synthase activity was constant and independent of thiol concentrations. In Western blot, CBS protein was clearly identified in freshly isolated PBMC. CBS protein level and activity increased with incubation time, upon stimulation, and similar to intracellular homocysteine, depending on intra- and extracellular homocysteine and glutathione concentrations. According to our knowledge, this is the first evidence that certifies homocysteine metabolism and regulatory role of CBS activity to keep balanced intracellular homocysteine level in resting PBMC. Homocysteine, released by PBMC, in turn can modulate its functions contributing to the development of hyperhomocysteinemia-induced diseases.

AB - Activated peripheral blood mononuclear cells (PBMC) release homocysteine and possess cystathionine β-synthase (CBS) activity; however, it was thought that there is no CBS in resting state. Previously, we found that nickel decreased intracellular homocysteine concentration in un-stimulated (e.g. resting) PBMC, suggesting that resting PBMC might also have active homocysteine metabolism. Here, we demonstrated that un-stimulated PBMC synthesize (incorporate l-[methyl-14C]methionine to DNA, lipids and proteins), release (increase extracellular homocysteine), and metabolize homocysteine. Intracellular homocysteine concentration varied with incubation time, depending on extracellular concentrations of methionine, homocysteine, and glutathione. Methionine synthase activity was constant and independent of thiol concentrations. In Western blot, CBS protein was clearly identified in freshly isolated PBMC. CBS protein level and activity increased with incubation time, upon stimulation, and similar to intracellular homocysteine, depending on intra- and extracellular homocysteine and glutathione concentrations. According to our knowledge, this is the first evidence that certifies homocysteine metabolism and regulatory role of CBS activity to keep balanced intracellular homocysteine level in resting PBMC. Homocysteine, released by PBMC, in turn can modulate its functions contributing to the development of hyperhomocysteinemia-induced diseases.

KW - Cystathionine β-synthase

KW - Extracellular homocysteine

KW - Glutathione

KW - Intracellular homocysteine

KW - Methionine

KW - PBMC

UR - http://www.scopus.com/inward/record.url?scp=84862771428&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862771428&partnerID=8YFLogxK

U2 - 10.1007/s00726-011-1080-2

DO - 10.1007/s00726-011-1080-2

M3 - Article

C2 - 21938399

AN - SCOPUS:84862771428

VL - 43

SP - 317

EP - 326

JO - Amino Acids

JF - Amino Acids

SN - 0939-4451

IS - 1

ER -