Kenneth W. Reed

Conformations of carnitine and acetylcarnitine and the relationship to mitochondrial transport of fatty acids

Abstract The conformations of carnitine and acetylcarnitine by EHT and CNDO/2 molecular orbital calculations show that carnitine has two low energy conformers. One of these is an extended conformer corresponding to a charge separated species, while the other is a folded conformer having a charged onium head and carboxylate anion in close proximity forming an internal ionic bond. These results suggest that the folded conformation is responsible for the active transport of acetyl- and acyl-carnitine by enzymes which transfer acyl groups into the mitochondria for subsequent fatty acid oxidation.

Conformational analysis of the reverse ester of acetylcholine, cholinergic potency, and cholinergic models

Abstract 1. 1. The conformational energy profile of the reverse ester of acetylcholine, a potent nicotinic agonist, was studied using EHT and PCILO molecular orbital calculations. 2. 2. The preferred conformation calculated by EHT has T1 = T2 = 180°, which is an extended molecule. 3. 3. The PCILO calculated preferred conformer has T1 = T2 = 60°, which corresponds to a folded molecule. 4. 4. The calculated preferred conformers do not match the preferred conformer given by X-ray crystallography. 5. 5. Comparison of the preferred conformations with the cholinergic potency of the reverse ester reveals that the models developed by Kier and by Chothia & Pauling for muscarinic and nicotinic activity cannot explain the activity of the reverse ester. 6. 6. A model based on the flexibility of the receptors and of the cholinergic molecules and electronic similarities in requisite atomic centers is necessary to explain the activity satisfactorily.

Radiolabeled 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine—I. Synthesis and purification

The purpose of this investigation was to synthesize and purify radiolabeled 9- or 10-monoiodostearyl carnitine for potential use as a perfusion and metabolic imaging agent for the heart. Oleic acid was iodinated via a free radical addition reaction of HI across the double bond to give 9- or 10-monoiodostearic acid which in turn was esterified with carnitine. The identity of 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine was determined using nuclear magnetic resonance (NMR), infrared (i.r.), ultraviolet (u.v.), and mass spectroscopy. The purity of the fatty acid and carnitine ester was established by thin layer chromatography. 9- or 10-Monoiodo[125I]stearic acid and 9- or 10-monoiodo[125I]stearyl carnitine were synthesized via the isotopic exchange of 125I for cold iodine bonded to 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine.