The vascular system transports components essential to the survival of the
individual and acts as a barrier to substances that may injure the organism.
Atherosclerosis is a dynamic, lesion producing disease of the arterial system that
compromises the functioning of the organ by occlusive and thrombogenic
processes. This investigation was undertaken to elucidate some of the normal
biochemical processes related to the development of atherosclerosis. A significant
part of the investigation was directed toward developing and combining methods
and protocols to obtain the data in a concerted manner.
A postmitochondnal supernatant of bovine aorta, using mevalonate-2-�����C as
the substrate, was employed in the investigation. Methods included paper, thin
layer, and silica gel chromatography; gel filtration, high performance liquid
chromatography (HPLC), and mass spectrometry.
This current research demonstrated direct incorporation of mevalonate-2-
�����C into the trans-methyiglutaconic shunt intermediates. The aorta also contains
alcohol dehydrogenase activity, which converts dimethylallyl alcohol and
isopentenol to dimethylacrylic acid, a constituent of the trans-methylgiutaconate
Small, radioactive peptides, named Nketewa as a group, were biosynthesized
using mevalonate-2-�����C as the substrate. They were shown to pass through a 1000 D
membrane. Acid hydrolysis and dabsyl-HPLC analysis defined the composition of the
Nketewa peptides. One such peptide, Nketewa 1, had a molecular weight of 1038 and a
sequence of his-gly-val-cys-phe-ala-ser-met (HGVCFASM), with a farnesyl group linked
via thioether linkage to the cysteine residue.
Methods were developed for the concerted investigation of the trans-methylglutaconate
shunt, the isolation of mevalonate-2-�����C labeled peptides, and
characteristics of neutral and acidic metabolites of mevalonate. The question as to
whether or not mevalonate was the direct precursor was answered in the affirmative.
These results contribute to the understanding of the biochemistry of the vessel wall and
the associated atherogenic processes. Mevalonate-derived volatile and acidic compounds
may represent an alternate metabolic pathway. The prenylated Nicetewa peptide may be,
as are other prenylated peptides, participants in the intracellular signaling process, release
of cytokines, expansion of extracellular matrix, and calcium release. / Graduation date: 2001
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/32639 |
| Date | 03 May 2001 |
| Creators | Walsh, Marilyn L. |
| Contributors | Gamble, Wilbert |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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