Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Catechol-O-methyltransferase: effects of the val108met polymorphism on protein turnover in human cells.

Authors: Doyle, Anne E; Yager, James D

Published In Biochim Biophys Acta, (2008 Jan)

Abstract: A single nucleotide polymorphism in the human COMT (catechol-O-methyltransferase) gene has been associated with increased risk for breast cancer and several CNS diseases and disorders. The G to A polymorphism causes a valine (val) to methionine (met) substitution at codon 108 soluble - (S)/158 membrane - (MB)-COMT, generating alleles encoding high and low-activity forms of the enzyme, COMT H and COMT L, respectively. Tissues and cells with a COMT LL genotype have decreased COMT activity compared to COMT HH cells. Previously, we reported that the decreased activity was due to decreased amounts of S-COMT L protein in human hepatocytes. In this study, we investigated the role of S-COMT protein synthesis and turnover as determinates of reduced COMT protein in COMT LL compared to COMT HH cells. No association between S-COMT protein synthesis and COMT genotype was detected. Using a pulse-chase protocol, the half-life of S-COMT H was determined to be 4.7 days, which was considerably longer than expected from the half-lives of other phase 2 enzyme proteins. The half-life of S-COMT L compared to S-COMT H protein was significantly shorter at 3.0 days, but the difference was affected by the medium used during the chase period. These results suggest that increased turnover may contribute to reduced COMT activity in cells and tissues from COMT LL individuals. Subtle differences appear to be able to affect the stability of the S-COMT L protein, and this may contribute to the differences observed in epidemiological studies on the association of this polymorphism with breast cancer risk.

PubMed ID: 17980711 Exiting the NIEHS site

MeSH Terms: Amino Acid Substitution; Blotting, Western; Catechol O-Methyltransferase/genetics*; Catechol O-Methyltransferase/metabolism*; Cell Line; Genotype; Humans; Immunoprecipitation; Methionine/genetics; Polymorphism, Single Nucleotide*; Valine/genetics

Back
to Top