From 1912 to 1915 the work of Pringsheim28 has helped to establish more firmly than ever the theory of the great molecular complexity of starch. By fermentation and hydrolysis of starch, under different conditions, he obtained several dextrins which were tetraand hexa-polymers of the simple dextrin molecule and similar to those isolated by Schardinger :29

From his experimental results he concludes that these dextrins

or "amyloses" have a ring structure, such as

and that they indicate that starch itself, and the non-reducing dextrins which are not fermented by yeast, contain the ring which can be opened only by special ferments.

In the light of all the observed properties of starch, we are obliged to accept the hypothesis that the molecule of this substance is large and very complex. Further experimental work, perhaps from the synthetical standpoint, will doubtless throw much more light upon the limits of magnitude of the molecule.

THE BEHAVIOR OF TARTARIC ACID AND THE TARTRATES IN THE ANIMAL ORGANISM

MAX KAHN

Introduction. In a recent paper by Carles,1 attention was drawn to the important part played by tartaric acid in wine manufacture, and a prophesy was made that within ten years the consumption of tartaric acid would be increased ten-fold. Tartaric acid and tartrates are used extensively, not only in wines but also in baking powders, in medicated waters and in candies. Comparatively little experimental work has been done on the pharmacology of tartaric acid and tartrates. The importance of exact knowledge in these connections is evident.

Dextro-tartaric acid was isolated first by Scheele, in 1768, and obtained in crystalline form by Retzius, in 1770, who designated it Sal essentiale tartari. Its composition and salts were studied by Gay-Lussac, Berzelius, and others; its optical properties, especially, by Biot (1815) and Pasteur (1841).2 Four optical isomers are known: dextro-, levo-, para- (racemic), and meso-tartaric acids.

Tartaric acid is one of the most widely distributed acids in the plant kingdom. It is present in the free state, or in the form of salts, in grapes, mountain-ash berries, tamarinds, tomatoes, cucumbers, potatoes, black pepper, pineapple and in leguminous plants.5 It has also been found in grape leaves, senna leaves, liverwort, ferns, beet juice, and fungi.

Behavior toward bacteria and fungi. Tartaric acid is produced, in the fermentation of fruit and grape juice, by the Apiculatus yeast, in which process carbohydrates are oxidized to tartaric acid. Calcium tartrate may be fermented, by the Bacillus tartaricus, to acetic acid, succinic acid, carbon dioxid and hydrogen.10 In the presence of ammonium nitrate, tartaric acid is fermented to propionic acid, acetic acid and carbon dioxid.11

Certain yeasts use tartaric acid as food, absorbing it in their growth.12 Pasteur13 found that Penicillium glaucum so affects p-tartaric acid (racemic) that it is changed to l-tartaric acid. Yeast ferments d-tartaric acid much more easily than the I form. The final carbonaceous product in the catabolism of tartaric acid by yeast is carbon dioxid.14 The peculiar affinity of yeast for the d-acid is quite significant, as will be seen below, where the metabolism of the various tartaric acids in the animal body is considered.

The mycoderms have no effect on tartaric acid.15 According to Waterman, 16 1- and d-tartaric acids may be utilized by Aspergillus niger as a source of carbon. Racemic acid is scarcely attacked by this organism but, after a prolonged period, mutation occurs. Neuberg and Czapski16a found that a concentration of 0.45 M of d-tartaric acid retards the fermentation of glucose.

General observations on toxicity. Certain of the earlier writers on the toxicology of tartaric acid considered this substance entirely non-poisonous. Christison11 concluded, from the results of an experiment by him and Coindet, in which they administered per os to a cat 3.75 gm. of tartaric acid dissolved in water, that this acid is wholly non-toxic. He also cited the experience of Dr. Sibbald, of Edinburgh, who accidentally ingested 22.5 gm. of the acid without suffering any ill effects. Wibmer stated that tartaric acid is injurious to the alimentary canal, hindering digestion, being more toxic, in these relations, than citric acid; also more diuretic than the latter acid. 18

Soon after the appearance of Wibmer's publication, certain cases of fatal poisoning were reported. In Watkins' case, 19 a young man, 24 years of age, took 30 gm. of tartaric acid in mistake for bitter salts. He suffered from violent pains and debility, and died on the ninth day. Devergie20 described another case of fatal poisoning with tartaric acid. Belloc21 wrote of a case of poisoning by Rochelle salt.

These cases caused a change in the attitude of toxicologists toward the tartaric acids. Orfila22 regarded them as very irritating and therefore considered them toxic. He also treated a patient who, when intoxicated, took 120 gm. of potassium tartrate and died on the fourth day afterward. Van Hasselt 23 regarded tartaric acid as toxic only in large doses. He considered it neither more nor less toxic than citric acid. He described its effects as resembling those of oxalic acid poisoning, differing only in a slower rate in the initiation of the symptoms. Hermann24 expressed the opinion that tartaric acid is toxic only in the free state; when in union with a base, its toxicity is that of the base to which it is attached. Jaksch25 stated that tartaric acid causes gastro-intestinal catarrh, with cramps and diarrhea. He did not mention the dose.

Trevithick26 reported the case of a woman, 67 years old, who took 12 gm. of tartaric acid by mistake. She suffered pains all over the body, vomiting and diarrhea ensuing. On the fourth day delirium developed, temperature became subnormal, pulse very weak. Death occurred on the seventh day.

Experimental toxicology. Mitscherlich was one of the first to conduct a series of experiments to determine the toxicity of tartaric acid. In his work on rabbits and cats, he found that Io gm. of the acid were necessary to kill a rabbit, when the substance was administered per os. In a cat, 5 gm. failed to induce symptoms. He also found that rabbits are more susceptible to citric acid than to tartaric, 5 gm. of the former being sufficient to cause death.

After painting the skin of a frog with dilute citric or tartaric acid, Goltz and Bobrick28 observed very marked slowing of the heart, with final stoppage.

In 1893, Chabrié, 29 investigating the differences in toxicity of the various stereoisomeric tartaric acids, found that l-tartaric acid is the most toxic, whereas d-tartaric acid is only half as toxic. He determined the lethal dose for rabbits in the following way: Certain quantities of the acids were necessary to kill rabbits of the same weight in a certain time. There was a definite ratio between these

I

X

doses, which he expressed by the function. He suggested the

where p is the dose used, P the weight of the animal in gm., and T the time in minutes. From his experiments he found,

X(1) = 0.031;

X(d) = 0.014;

X(1) = 0.008;

X(m) = 0.006.

Attention has already been called to the difference in the behavior of these stereoisomeres in yeast fermentation. Chabrié also reported that p-tartaric acid (racemic) is only one fourth as toxic as the d-acid, and that the m-acid is wholly non-toxic.