Hugh David Niall

The Chemistry of Parathyroid Hormone and the Calcitonins

Publisher Summary This chapter discusses the chemistry of parathyroid hormone and the calcitonins. In the last several years, there have been striking advances in knowledge of the chemistry of parathyroid hormone and calcitonin. The complete amino acid sequence of the major form of bovine and porcine parathyroid hormone has been determined, and, as well, the complete structure of porcine, human, ovine, bovine, and three different isohormonal forms of salmon calcitonin. These advances are potentially of considerable interest and importance to investigators and clinicians concerned with the physiology, mode of action, and clinical significance of parathyroid hormone and calcitonin. The significance of these chemical advances, particularly the availability of highly potent and completely homogeneous preparations of synthetic parathyroid hormone and calcitonin can best be appreciated in terms of a historical perspective. Intensive physiological and clinical investigations have established the importance of parathyroid hormone in normal calcium homeostasis and in certain diseases involving disorders of calcium and bone metabolism. The hormone acts to increase rates of bone resportion and to reduce the rate of urinary calcium loss, thereby maintaining serum calcium and preventing hypocalcemia.

The application of a fluorinated isothiocyanate as coupling agent in the Edman degradation

Abstract Pentafluorophenylisothiocyanate was used as a coupling agent in Edman degradation. All the pentafluorophenylthiohydantoins, except for arginine and histidine, could be identified by gas chromatography with the use of a one-column system. Their ultraviolet spectra and mobilities in thin-layer systems were studied. This new coupling agent was successfully used in short degradations of peptides and alternating with phenylthiocyanate in the degradation of a complex mixture of peptides of salmon calcitonin.

Parathyroid Hormone: Chemical and Immunochemical Studies of the Active Molecular Species

This chapter discusses the chemical and immunochemical studies of the active molecular species. Bovine parathyroid hormone has been isolated in the form of three homogeneous isohormones and the porcine hormone has also been purified. The presence of hormonal fragments appears to explain the nonparallel responses produced in the radioimmunoassay by hormone in peripheral plasma. It is observed that such nonparallel slopes using one or more antisera in the radioimmunoassay with most peripheral plasma samples tested, while hormone in blood directly from the parathyroid glands has been, without exception, completely parallel with hormone extracted from the glands. One explanation for the nonparallel slopes seen in the radioimmunoassay of parathyroid hormone in peripheral plasma may be the presence in the assay antiserum of two or more antibodies with different antigenic determinants and different affinity constants for the hormone. Thus, when one fragment is present at greater concentrations than the other, a change in displacement slope can be predicted. Alternately, the cleavage of the intact hormone at an important antigenic site of the molecule may change the displacement slopes.

Chemistry and Physiology of the Calcitonins: Some Recent Advances

This chapter discusses the chemical and physiological properties of calcitonins. Porcine calcitonin disappears with an initial half-time of 2–5 min, compared with 21 min for salmon calcitonin. Comparable studies including human calcitonin as well as porcine and salmon show that the disappearance rate of human hormone was intermediate between the other two. In all cases, the in vivo half-times are very much faster than those observed during in vitro plasma incubation. Hence, breakdown in peripheral plasma cannot alone be responsible for degradation of calcitonins in vivo. These studies all suggest, however, that at least a part of the explanation for the increased potency of salmon calcitonin may be increased resistance to destruction, leading to longer maintenance of effective blood levels of calcitonin.

Comparative biochemistry of parathyroid hormone and calcitonin

Abstract This is a brief summary of the current state of our knowledge concerning the chemical nature of parathyroid hormone and calcitonin from several vertebrate species, primarily mammalian. Bovine and porcine parathyroid hormone have been isolated in pure form and their structures analyzed. The complete amino acid suquence of porcine, human, ovine, bovine, and three different isohormonal forms of salmon calcitonin have been determined. Synthesis has been achieved of porcine, human, and salmon calcitonin, and, most recently, the biologically active amino terminal portion of bovine and porcine parathyroid hormone.