This research project involves an examination of the chemistry and biochemistry of aluminum ions and an assessment of their possible involvement in neurological dysfunctions such as Alzheimer's disease and dialysis encephalopathy. The possible involvement of aluminum ions as a cariostatic agent in the prevention of dental plaque formation will also be addressed. An additional long term objective is an evaluation of the possible interference of calcium metabolism by excess aluminum.
The specific aims of this project are to: examine the complexation of aluminum by nucleotides to provide the basis for understanding the binding of aluminum by nucleic acids in brain nerve cells; survey the inhibition of phosphoryl-transferring enzymes by aluminum-ATP and the inhibition, by aluminum ions, of enzymes involved in regulating the levels of neurotransmitters to obtain information on the possible sites of inhibition of metabolism by aluminum; study the complexation of aluminum ions by several groups of simple, multidentate chelators to aid in the design of specific aluminum chelators that can function in anti-aluminum drug therapy.
The specific aims of this project will be addressed by binding studies that will provide quantitative information about the number of affinity of binding sites for aluminum ions to enzymes, nucleotides, and multidentate chelators. Kinetic studies will be conducted that will evaluate the effect of aluminum complexes on the activity of enzymes that function in phosphoryl-transfer reactions and in the regulation of the levels of certain neurotransmitters. Magnetic resonance studies will be carried out that will yield information about the solution structures of these aluminum complexes. Together these techniques will provide information that will dramatically improve our understanding of the chemistry and biochemistry of aluminum ions, and should provide the basis for more detailed studies into the effects of aluminum and other metal ions on metabolism.
| Kim, M H; Lu, M; Kelly, M et al. (2000) Mutational analysis of basic residues in the rat vesicular acetylcholine transporter. Identification of a transmembrane ion pair and evidence that histidine is not involved in proton translocation. J Biol Chem 275:6175-80 |
| Furumo, N C; Viola, R E (1989) Aluminum-adenine nucleotides as alternate substrates for creatine kinase. Arch Biochem Biophys 275:33-9 |
