Masters Theses

Abstract

Signs of extensive atherosclerotic disease in many subjects with elevated homocysteine (Hcys) levels have been observed. Since metals are known to catalyze the auto-oxidation of thiols, this study attempts to investigate the catalytic effect endogenous copper ions might have on accelerating Hcys auto-oxidation and its implications to Hcys’ link as a risk factor for atherosclerosis.

Hcys alone did not appear to be very toxic to Chinese hamster ovary (CHO) cells in short-term assays. Hcys auto-oxidation was clearly accelerated by the addition of copper ions to the media. The combination of Hcys with copper induces an oxidative stress on CHO cells as indicated by various cell-based toxicity assays. Hcys alone in the media resulted in up to a sixfold increase in glutathione/glutathione disulfide (GSH/GSSG) ratios. This suggests that either Hcys up-regulates GSH synthesis or it inhibits glutathione peroxidase (GPx), the enzyme responsible for allowing GSH to scavenge peroxides by producing GSSG.

The animal model was fed a vitamin B6, B12, and folic acid-deficient diet to induce high levels of Hcys in an attempt to mimic diet-induced homocysteinemia. Common symptoms were seen solely in the deficient diet groups indicative of a vitamin B deficiency, and, as indicated by the lipid peroxidation (LPO) assay, LPO is occurring in the blood and brain. Even under the oxidative stress of copper-catalyzed Hcys auto-oxidation, GSH levels still increased in the B-deprived groups, suggesting that Hcys inhibits glutathione peroxidase. Hcys appears to have a multifactorial toxicity in that it releases reactive oxygen species during copper- catalyzed auto-oxidation to induce an oxidative stress and it renders GPx inactive, which is responsible for combating this resultant oxidative insult"--Abstract, p. iii.

Advisor(s)

Ercal, Nuran

Committee Member(s)

Collier, Harvest L.
Westenberg, David J.

Department(s)

Chemistry

Degree Name

M.S. in Chemistry

Publisher

University of Missouri--Rolla

Publication Date

Fall 2001

Pagination

x, 67 pages

Note about bibliography

Includes bibliographical references (pages 59-66).

Rights

© 2001 Douglas Robert Krutil, All rights reserved.

Document Type

Thesis - Restricted Access

File Type

text

Language

English

Thesis Number

T 7968

Print OCLC #

48797609

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