ILLUSTRATIONS.

PLATE I. Liver sections of organic-phosphorus-fed rabbit No. 1. Fig. 1.—Magnification 60 diameters. Fig. 2.-Magnification 175 diameters.... II. Liver sections of organic-phosphorus-fed rabbit No. 2. Fig. 1.—Magnification 60 diameters. Fig. 2.—Magnification 175 diameters.... III. Liver sections of inorganic-phosphorus-fed rabbit No. 4. Fig. 1.-Magnification 60 diameters. Fig. 2.-Magnification 175 diameters...

4

Page.

60

60

60

METABOLISM OF ORGANIC AND INORGANIC

PHOSPHORUS.

REVIEW OF THE LITERATURE.

Much work has already been done on phosphorus metabolism, both in regard to the inorganic and organic forms of phosphorus, and many investigations have been recorded showing the advantages of the various organic forms, such as lecithin, glycero-phosphoric acid, phytin, etc. Most of this work has been done abroad, although some has been published in this country, notably the researches of Jordan, Patten, and Hart;a Mendel and Underhill; and Le Clerc and Cook. It seemed advisable, therefore, to present a general survey of the contributions previously made on this mooted question.

PHOSPHORUS COMPOUNDS.

In speaking of phosphorus compounds, Bunged states that certain of them probably should be regarded as essential organic food substances for man; also that in all animal and vegetable tissues, in every cell are found two complex organic compounds which are rich in phosphorus, namely, the lecithins and the nucleins.

According to the recent recommendations of the joint committee of the American Physiological Society and the American Society of Biological Chemists on protein nomenclature, the word "proteid" should be abandoned and the word "protein" should designate that group of substances which consists essentially of combinations of a-amino acids and their derivatives.

The conjugated proteins are divided into (a) nucleo-proteins, (b) glyco-proteins, (c) phospho-proteins, (d) hemoglobins, (e) lecithoproteins. The nucleo-proteins are compounds of one or more protein molecules with a nucleic acid. The phospho-proteins are compounds of the protein molecule with some, as yet unidentified, phosphorus-containing substance other than a nucleic acid or lecithin. The lecitho-proteins are compounds of the protein molecule with lecithins (lecithans, phosphatids).

a Amer. J. Physiol., 1906, 16: 268.

b Ibid., 17: 75.

J. Biol. Chem., 1906, 2: 203.

d Physiologic and Pathologic Chemistry, 2d ed., 1902.

LECITHINS.

The lecithins are ester compounds which may be regarded as having been formed by the union of one molecule of glycerol with two molecules of a fatty acid (stearic acid, palmitic acid, or oleic acid), one molecule of phosphoric acid, and one molecule of cholin, with the loss of four molecules of water. The formula for lecithin is C1HNPO. The lecithin radical contains one atom of nitrogen for every atom of phosphorus.

44

Cholin is an ammonium base, the composition of which is accurately known. When heated it splits into glycol (ethylene alcohol), and trimethylamin. Its synthesis corresponds with this decomposition. Wurtza produced it by the action of ethylene oxid and water on trimethylamin. In the animal kingdom cholin has, up to the present time, been found only in lecithin. It was first obtained by Strecker from the bile, which contains lecithin, and hence was called cholin. Liebreich found it among the products of the decomposition of phosphorus compounds from brain tissue. Diaconow d showed that it was a product of the decomposition of lecithin. In the new tissues of plants cholin is found in other combinations as well as in lecithin. At present but little is known about the part which the lecithins play in the vital functions.

An important question is whether the lecithins of the body tissues are produced from the lecithins of the food or by synthesis from other materials such as fat, protein, and phosphoric acid. It has been ascertained from experiments on artificial pancreatic digestion that the lecithins take up water and readily split up into glycerophosphoric acid, fatty acids, and cholin. It is not yet known whether this decomposition is complete in normal digestion, or a portion is absorbed unchanged, and if so, how large a portion; whether only the undecomposed part, when absorbed, can be utilized in the building up of the tissues, or the products of decomposition which are absorbed again become united; or finally whether lecithin may also be formed from other material. The absorption of lecithin or of its products of decomposition is complete, according to Bunge, as he states that neither lecithin nor glycero-phosphoric acid can be found in the feces. More recent work, however, by Long seems to show that the feces sometimes contain lecithin in considerable quantities. The presence of lecithin in milk, eggs, and many other foods indicates that this substance is essential in nutrition.

a Centrbl. med. Wissensch., 1868, 6: 69, 431.

Ann. Chem. Pharm., 1862, 123: 353; 1868, 148: 77.

c Ibid., 1865, 134: 29.

d Centrbl. med. Wissensch., 1868, 6:97, 434.

J. Amer. Chem. Soc., 1906, 28: 704; Long and Johnson, ibid., 1499.

NUCLEO-PROTEINS.

By this name are designated those compound proteins which yield true nucleins on pepsin digestion and which, on cleavage with alkali, yield protein and nucleic acid. The nucleo-proteins seem to be widely distributed in the animal body. They occur chiefly in the cell nuclei, but they also often occur in the protoplasm. They may pass into the animal fluids on the destruction of the cells; hence nucleo-proteins have also been found in blood serum. They may be considered as combinations of a protein nucleus with a side chain which Kossel calls the "prostetic group." This side chain, which contains the phosphorus, yields on the decomposition of many nucleoproteins, such as that from the yeast cell or from the pancreas,c besides nuclein bases, also reducing substances, which form crystalline combinations with phenyl-hydrazin. The nucleo-proteins contain from 0.5 to 1.6 per cent of phosphorus.

The nucleo-proteins split into a nuclein and an albumin radicle and the nuclein radicle is further split into nucleic acid and albumin. The nucleic acids on cleavage yield in addition to the purin bases three simple pyrimidin derivatives, uracil, cytosin, and thymin. In a recent article by Osborne and Heyl it appears that all but onesixteenth of the nitrogen of nucleic acid probably belongs to guanin, adenin, cytocin, and uracil, of which one molecule of each is present for every four atoms of phosphorus.

d

It is important to distinguish between the nucleo-proteins and the pseudo nucleo-proteins. The latter bodies are obtained as an insoluble residue on digestion of certain nucleo-albumins or phospho-glycoproteins with pepsin hydrochloric acid. They contain phosphorus but yield no nuclein bases. Among the pseudo nucleo-proteins may be mentioned phospho-proteins and lecitho-proteins. These substances are often fed in the form of casein or vitellin in metabolism experiments.

NUCLEINS.

The generic name of nuclein has been bestowed upon a large number of very different organic phosphorus compounds, which are to be found in all animal and vegetable tissues, being especially abundant in the nuclei of cells. The nucleins contain about 5 per cent of phosphorus and are formed by the cleavage of nucleo-protein. The nucleins are acids, and the phosphorus is given off as phosphoric acid on boiling with water, and more rapidly on boiling with alkalies or acids. But the organic substances which are combined with the

a Arch. Anat. Physiol., Physiol. Abt., 1893, p. 157.

b Ibid., 1891, p. 359.

c Hammarsten, Zts. Physiol. Chem., 1894, 19 : 19.

d Amer. J. Physiol., 1908, 21: 157.

phosphoric acid appear to be of varying characters. Most nucleins are protein compounds, although a few do not contain protein. Nucleins appear to occur mostly in the tissues, not in a free state, but as compounds with protein as nucleo-albumins, and perhaps also with lecithin, and the gastric digestion separates them from these bodies.

Whether the nucleins of the body tissues arise from the nucleins of food (in which case they would rank among the number of essential food substances), or whether the nucleins are formed in the body by synthesis, is a question of great importance, about which, as in the case of the mode in which the lecithins originate, very little is known. The extensive observations by Miescher a on Rhine salmon seem to show that the nucleins as well as the lecithins arise in the animal body by synthesis.

PHOSPHO-GLUCO-PROTEINS.

This group includes the phosphorized gluco-proteins. These compound proteins are decomposed by pepsin digestion and split off paraor pseudo-nuclein substances, similar to nucleo-albumins. They differ from the nucleo-albumins in that they yield a reducing substance on boiling with acids, and from the nucleo-proteins in that they do not yield purin bases.

Only two phosphorized gluco-proteins are known at the present time. Ichthulin, which occurs in carp eggs and was studied by Walter, was considered by him as vitellin for a time. In regard to solubilities, ichthulin behaves like a globulin. Walter prepared a reducing substance from the para-nuclein of ichthulin, which gave a crystalline combination with phenylhydrazin. The other phosphogluco-protein is helico-protein, obtained from the glands of the small snail Helix pomatia.

INORGANIC PHOSPHORUS.

In regard to phosphoric acid Hammarsten states that there seems to be no doubt that its importance lies chiefly in the fact that it takes part in the formation of nucleins and thereby indirectly makes possible the processes of growth and division which are dependent upon the cell nuclei. Loew has shown, by means of cultivation experiments on the alga Spirogyra, that only by supplying phosphates (in this case potassium phosphate was used) was the nutrition of the cell nucleus made possible, and thereby the growth and division of the cells. The cells of the Spirogyra can be kept alive, and indeed produce

a Cited in Hammarsten's Textbook of Physiological Chemistry, New York, 1908. b Zts. physiol. Chem., 1891, 15 : 477.

C Physiological Chemistry, 2d ed., 1898.

d Biol. Centrbl., 1891, 11: 269.