Sulfur amino acids have critical function as intracellular redox buffers and maintain
homeostasis in the external milieu by combating oxidative stress. Synthesis of
glutathione (GSH) is regulated at a substrate level by cysteine, which is synthesized by
homocysteine via the transsulfuration pathway. Oxidative stress and diminished
glutathione pools play a sustained role in the pathogenesis of acute pancreatitis.
One of the aims of this study was to experimentally address the temporal relationship
between plasma sulfur amino acid levels in patients suffering from acute pancreatitis.
The data indicated low concentration of cysteine initially, at levels similar to those of
healthy controls. Glutathione was found reduced whilst cysteinyl-glycine and ¿-
glutamyl transpeptidase activity were increased in both mild and severe attacks. As the
disease progressed, glutathione and cysteinyl-glycine were further increased in mild
attacks and cysteine levels correlated with homocysteine and ¿-glutamyl transpeptidase
activity. The progress of severe attacks was associated with glutathione depletion,
reduced ¿-glutamyl transpeptidase activity and increased cysteinyl-glycine, that
correlated with glutathione depletion. The corollary that ample supply of cysteine and
cysteinly-glycine does not contribute towards glutathione synthesis in acute pancreatitis
poses an important issue that merits resolution. Heightened oxidative stress and
depletion of glutathione rationalized the progression of disease in severe attacks.
An upsurge that reactive oxygen species can shift redox state of cells is determined by
the ratio of the abundant redox couples reduced and oxidized glutathione (GSH: GSSG)
in cell. The study reported a novel methodology for quantification of total oxidized
glutathione (tGSSG) and total glutathione (tGSH) in whole blood using reverse phase
high performance liquid chromatography. The novelty of the method is ascertained by
the use of a mercaptan scavenger 1, methyl-2-vinyl-pyridinium trifluromethanesulfonate
for the total oxidized glutathione determination. The results reported permit quantitation
of tGSSG and tGSH and was applied to a control group.
Finally, the study was also focussed in developing a liquid chromatography-mass
spectrometric method to evaluate free and conjugated bile acids in patients suffering
from various degrees of cholestatic-hepatobiliary disorders. The study reported low
levels of ursodeoxycholic acid (UDCA) and slightly high levels of lithocholic acid
(LCA). All the primary bile acids seem to be conjugated with glycine and taurine amino
acid.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/4434 |
| Date | January 2010 |
| Creators | Srinivasan, Asha R. |
| Contributors | Nicolaou, Anna |
| Publisher | University of Bradford, School of Pharmacy |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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