NMR studies of electrostatic potential distribution around biologically important molecules.

A new experimental approach has been developed to study the distribution of local electrostatic potential around specific protons in biologically important molecules. The approach is the development of a method denoted as "spin label/spin probe," which was proposed by one of us (. Mol. Biol. 6:498-507). The proposed method is based upon the quantitative measurement of the contribution of differently charged nitroxide probes to the spin lattice relaxation rate (1/T1) of protons in the molecule of interest, followed by calculation of local electrostatic potential using the classical Debye equation. In parallel, the theoretical calculation of potential distribution with the use of the MacSpartan Plus 1.0 program has been performed. Application of the method to solutions of simple organic molecules (aliphatic and aromatic alcohols, aliphatic carboxylates (propionate anion), and protonated ethyl amine and imidazole) allowed us to estimate the effective potential around the molecules under investigation. These were found to be in good agreement with theoretically expected values. This technique was then applied to zwitterionic amino acids bearing neutral and charged side chains (glycine, lysine, histidine, and aspartic acid). The reliability of the general approach is proved by the data presented in this paper. Application of this new methodology can afford insight into the biochemical significance of electrostatic effects in biological systems.

Pituitary insufficiency following head injury.

A 32-year-old man developed panhypopituitarism and diabetes insipidus shortly after sustaining a head injury. Hormonal investigation showed that basal prolactin levels were moderately elevated the first two years after the accident, but later returned to normal. There was no rise in prolactin after administration on chlorpromazine, and the response to thyrotropin-releasing hormone was attenuated. Basal luteinizing hormone and follicle-stimulating hormone levels were low and there was no change after administration of luteinizing-hormone-releasing hormone. There was also no growth hormone elevation following arginine infusion. On the other hand, there was a normal but delayed elevation of thyrotropin in response to thyrotropin-releasing hormone. Appropriate stimulation tests showed normal responsiveness of the thyroid, adrenals and testes. These findings are compatible with an injury to the pituitary stalk, damaging the neurohypophyseal tract and affecting the blood supply to the pituitary gland.