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Molecular Analyses of Melanins and Neuromelanins
- Abstract:
Melanins and neuromelanins (NM) are biological pigments composed of dihydroxyindole/ dihydroxyindole-carboxylic acids and dopamine units, respectively. Whereas much is known regarding the physical and spectroscopic properties of melanins and neuromelanins, limited details regarding the molecular composition exists. Both pigments contain metals, proteins, and lipids. This thesis describes two aspects of the molecular composition: the distribution of naturally occurring pyrrole acids in melanosomes and the lipid composition of ocular melanosomes and neuromelanins.
Tandem mass spectrometry and liquid chromatography were used to identify and quantify the water-soluble pyrrole acids present in Sepia , human hair, and bovine ocular melanosomes. This research demonstrates that pyrrole-2,3-dicarboxylic acid and pyrrole-2,3,5-tricarboxylic acid are naturally present in melanosomes. Additionally, this is the first establishment of pyrrole-2,3,4,5-tetracarboxylic acid as a naturally occurring pyrrole acid in melanosomes.
The second molecular component studied was the lipid profile. The lipid distribution of ocular melanosomes depends on their embryonic origin. Iris and choroid (uveal) melanosomes contained similar phospholipid compositions, with sphingomyelin as the major species. Retinal pigment epithelium melanosomal lipids differed significantly, with glycerophosphoethanolamine and docosahexanoic acids as the major components. The uniqueness of retinal melanosomes encouraged the subsequent studies on neuromelanin lipids.
In mapping the lipids of isolated NM from the substantia nigra (SN), dolichoic acid (dol-CA) was observed for the first time in a natural system. In the SN, dolichol (dol) and dol-CA were ~12% and 3% of the total NM weight, respectively. Next, dol and dol-CA were quantified in NMs isolated from six addition regions of the human brain. The total concentrations of dol and dol-CA were region-specific, yet the chain length distributions were comparable. Lipid profiles of these isolated NMs also included other oxidized dolichols (dol-ox), with covalent addition of 1-4 oxygen atoms onto the dol backbone, dol-CA plus one oxygen, and hydrogenation of double bonds on dol. The relative abundance and distribution of dol-ox was region-dependent.
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