- Title
- Synthesis and interaction of secondary N-nitrosamines with acetylcholinesterase
- Creator
- Mmutle, Tsietso Bernard
- Subject
- Chemistry, Physical and theoretical
- Subject
- Enzyme kinetics
- Date Issued
- 1991
- Date
- 1991
- Type
- Thesis
- Type
- Masters
- Type
- MSc
- Identifier
- vital:4058
- Identifier
- http://hdl.handle.net/10962/d1004119
- Identifier
- Chemistry, Physical and theoretical
- Identifier
- Enzyme kinetics
- Description
- Secondary N-nitrosamines: diphenylnitrosamine (DPhNA), dimethylnitrosamine (DMNA), diethylnitrosamine (DENA), dipropylnitrosamine (DPNA), dibutylnitrosamine (DBNA), diethanolnitrosamine (DEtNA), methylnitrosoglycine (MNGly), nitrosopyrrolidine (NPyr), nitrosomorpholine (NMor) and nitrosopiperidine (NPip) were synthesised and their interaction with acetylcholinesterase (AChE) was investigated. Analyses of kinetic results show that DMNA (Ki=34.78 μM); DENA (Ki=54.24 μM); DPNA(Ki=60.36 μM); DBNA(Ki=95.54 μM); DEtNA(Ki=43.68 μM)MNGly (Ki=30.18 μM); NPip (Ki=123 μM); NPyr (Ki=66.07 μM), NMor (Ki=73.93 μM) and DPhNA (Ki=20.32 μM) are competitive and reversible inhibitors of acetylcholinesterase, with respect to the substrate, acetylthiocholine chloride, ATChCl. With time they act as irreversible covalent inhibitors with dipropy1nitrosamine producing 72% inactivation after 60 minutes. Scatchard analyses of f1uorometric titrations, (Kd=0.75mM-4.09mM); gel chromatography (Kd=O. 80mM-4. 60mM) and equilibrium dia1ysis (Kd=O. 71mM- 4.21mM) for MNG1y, DMNA, DEtNA, DENA, DPNA, NPyr, DSNA, NMor and NPip show that these compounds have weaker affinity for the enzyme, as compared to the much tightly binding aromatic DPhNA, Kd values (0.65mM, 0.68mM and 0.68mM) for fluorometric experiments, gel chromatography and equilibrium dialysis respectively. In all cases, the number of binding sites of acetylcholinesterase averaged to four.
- Format
- 97 p.
- Format
- Publisher
- Rhodes University
- Publisher
- Faculty of Science, Biochemistry, Microbiology and Biotechnology
- Language
- English
- Rights
- Mmutle, Tsietso Bernard
- Hits: 891
- Visitors: 1014
- Downloads: 139
Collections
RU Department of Biochemistry, Microbiology and Biotechnology (end of 2014)
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCEPDF | 8 MB | Adobe Acrobat PDF | View Details Download |