Subtitle:

From Accuracy in Protein Synthesis to Cardiovascular Disease: The Role of Homocysteine

Publisher:

Committee on Biotechnology PAS ; Institute of Bioorganic Chemistry PAS

Abstract:

The non-protein amino acid homocysteine (Hey) enters the first step of protein synthesis and forms an aminoacyl-tRNA synthetase-bound homocysteinyladenylate (Hey-AMP). Direct incorporation of Hey into tRNA and protein is prevented by editing activities of aminoacyl-tRNA synthetases that convertHey-AMP into Hey thiolactone. Editing of Hey occurs in all cell types investigated, including human. S-Nitrosylation of Hey prevents its editing by MetRSand allows formation of S-nitroso-Hcy-tRNA'^^', as well as incorporation of Heyinto proteins at positions specified by methionine codons. This provides an example of how the genetic code can be expanded by invasion of the metioninęcoding pathway by Hey. Hey can also be incorporated into protein post-translationally by a facile reaction of Hey thiolactone with e-amino groups of proteinlysine residues. Hey is present in human blood proteins, such as hemoglobin,serum albumin, and y-globulins. Hey thiolactonase, a component of high-densitylipoprotein, minimizes protein N-homocysteinylation. Incorporation of Hey intoprotein provides plausible chemical mechanism by which elevated levels of Heycontribute to human cardiovascular disease.

Relation:

Biotechnologia, vol.58, 3 (2002)-.

Volume:

58

Issue:

3

Start page:

11

End page:

24

Detailed Resource Type:

Article

Format:

application/pdf

Resource Identifier:

0860-7796 ; oai:rcin.org.pl:137852 ; IChB B-54

Source:

Library of Institute of Bioorganic Chemistry PAS

Language:

pol

Language of abstract:

eng

Temporal coverage:

1988-2010

Rights:

Creative Commons Attribution BY-SA 4.0 license

Terms of use:

Copyright-protected material. [CC BY-SA 4.0] May be used within the scope specified in Creative Commons Attribution BY-SA 4.0 license, full text available at:

Digitizing institution:

Institute of Bioorganic Chemistry of the Polish Academy of Science

Original in:

Institute of Bioorganic Chemistry of the Polish Academy of Science

Projects co-financed by:

Operational Program Digital Poland, 2014-2020, Measure 2.3: Digital accessibility and usefulness of public sector information; funds from the European Regional Development Fund and national co-financing from the state budget.

Access:

Open