The relationship between calcium-phosphorus metabolism, the 'Krebs cycle' and steroid metabolism.

It has been shown in the course of the last few years that the number of factors playing a part in calcium-phosphorus (Ca-P) metabolism is far greater than had been known. It was found that the calcification of bones depends in the first place on the 'citric acid cycle' and on adenosine triphosphate (ATP) (oxidative phosphorylation) (Dickens, 1941; Albaum, Hirshfeld and Sobel, 1952; Dixon and Perkins, 1952; Marks, Hiatt and Shorr, 1953). Alkaline phosphatase intervenes chiefly in the processes concerned with the formation of the organic substance of the skeleton. Some factors as yet unknown (citrates ?) similarly regulate the action of the parathyroid hormone, an action which has not yet been accurately defined (Zweymiller, 1958). The role played by the parathyroid in classical and in vitamin D resistant rickets is still uncertain (Lamy, Royer, Frezal and Lestradet, 1958). Similarly, the action of vitamin D seems to be dependent on factors which regulate the sensitivity of the organism to its effect (Fanconi and Spahr, 1956). The suprarenals have acquired some degree of importance, as was shown in studies on idiopathic hypercalcaemia, on tetany occurring in newborn infants of diabetic mothers and on hypercalcaemia with osteosclerosis found in a number of cases of myxoedema (Gittleman, Pincus, Schmerzler and Saito, 1956; Winberg and Zetterstrom, 1956; Anderson, Brewis and Taylor, 1957; Royer, Lestradet and Habib, 1958; Zetterstrom and Arnhold, 1958). Cortisone acts as an antagonist of vitamin D by impairing the absorption of calcium from the intestines; another action of cortisone is to reduce the rate of tubular reabsorption of phosphorus (Roberts and Pitts, 1953). It is possible that there is a relationship between the suprarenals and the parathyroid glands, as suggested by cases of hypoparathyroidism associated with Addison's disease (Leonard, 1946; Papadatos and Klein, 1954; Whitaker, Landing, Esselborn and Williams, 1956). We have become conversant in recent years with the importance of the relationship between ossification, parathyroid hormone, vitamin D and the 'Krebs cycle' (Glanzmann, Meier and Walthard, 1946; Heinz, Miller and Rominger, 1947; Harrison and Harrison, 1952a; Nordio, Semach and Grego, 1956; de Toni, 1957). In rickets the citric acid level in the blood and urine is diminished (Harrison, 1954; Nordio et al., 1956). The same phenomenon is observed in idiopathic hypercalcaemia (Forfar, Balf, Maxwell and Tompsett, 1956; Nordio et al., 1956). Administration of vitamin D and, although less regularly, of parathormone leads to a rise in the citric acid level in blood and urine (Harrison and Harrison, 1952a; Steenbock and Bellin, 1953; Nordio et al., 1956). Considerable importance is attributed to the 'citric acid cycle' in the renal tubules in connexion with the regulation of the acid-base balance and the reabsorption of phosphorus, amino acids and glucose (Harrison and Harrison, 1941; Durand, Manzini, Bruni and Semach, 1956; Nordio et al., 1956). As is known, the synthesis of steroids has the 'Krebs cycle' as its starting point, and it may be possible to interpret the various disturbances of calcium-phosphorus metabolism also in terms of the Krebs cycle.