More recently Sternberg has formulated the hypothesis that B-oxybutyric acid is formed from proteid via amidobutyric acid, and that the latter is a decomposition product of albumen. Feeding with this acid produced a symptom complex that very much resembled diabetic coma. In the urine of such animals diacetic acid could be discovered by Gerhardt's reaction. Magnus-Levy objected to Sternberg's reasoning on the following grounds: in the first place the picture presented in cases that are intoxicated with amido-butyric acid differs in no way from the disease picture in other forms of intoxication which certain poisons that are in no way theoretically related to oxybutyric acid. In the second place, no one has ever demonstrated conclusively that amido-butyric acid is a product of the disintegration of proteids in the organism.

Finally, the assumption that amido-butyric acid is the mother substance of B-oxybutyric acid becomes altogether improbable when the quantities of B-oxybutyric acid that have been found in individual cases of diabetes are calculated for amido-butyric acid, a calculation that Magnus-Levy has performed in some of his investigations.

The fact, again, that acetone can be manufactured from gelatin (Blumenthal and Neuberg) or from albumen (Zuckelberger and von Jacksch) by active oxidation signifies nothing in regard to the origin of oxybutyric acid and its derivatives from albumen in the organism for the quantities of acetone that can be manufactured from albumen are altogether too small. In addition the fact that oxybutyric acid can be manufactured in this way in vitro demonstrates nothing in regard to its origin in vivo. We see, therefore, that on the basis of the facts that we possess we are forced to deny the possibility of acetone formation by simple oxidation or splitting of albumen. At the same time, we cannot deny that possibly the nitrogen-free radical of the albuminoids at first splits off atom groups that contain little carbon and that oxybutyric acid is finally formed from these groups by synthesis (see the formation of acetone bodies from the fatty acids below).

As the carbohydrates in the proteids cannot therefore be considered the mother substance of oxybutyric acid, only two possibilities remain, namely, that oxybutyric acid may be formed from fats (by degradation) or that it may be formed by synthesis from bodies containing two or three carbon atoms; in the latter case it would be immaterial whether these bodies were a product of the disassimilation of albumen or of fat (Magnus-Levy). The following facts seem to speak in favor of the former possibility:

From the investigations of Gelmuyden already quoted above, we know that if a subject is fed on a diet free from carbohydrates, the addition of fat to such a diet, or of fatty acids, increases the excretion of acetone. The original assumption of Gelmuyden that only the lower series of fatty acids are capable of exercising this effect has not been verified, for Schwarz, Mohr and Lob, etc., were able to show that neutral fats possessed the same power, although not to the same degree. The same is demonstrated by a large number of experiments that have been performed in diabetic subjects. (These investigations will soon be published by Dr. Satta from our laboratory.) Other experiments show that the quantity of free fatty acids cannot be the factor that determines the increase in the excretion of oxybutyric acid or of acetone, for in some of the cases more oxybutyric acid was excreted than butyric acid was administered. Besides, we know that in diabetics the enormous quantities of oxybutyric acid that are excreted cannot possibly be derived from preformed low fatty acids that were introduced with the food. The question therefore rises whether or not the catabolism of the higher fatty acids (of the food or of the organism itself) proceeds in such a way that the chain of atoms containing from 16 to 18 atoms of carbon is split and butyric acid formed in this way. Even if we assume this to be the case, the chemical interpretation of the process is not rendered any more clear, for the assumption that butyric acid is transformed into oxybutyric acid by simple oxydation is chemically inconceivable. It is a little more probable that the fatty acids are disassimilated until the stage of acetic acid with two atoms of carbon is reached and that later certain synthetic processes lead to the formation of oxybutyric acid. Other syntheses occurring with acetic acid, a body that is always present in the organism, are well known, and Cohn has actually assumed that in the case under discussion such a synthesis takes place.

This question has also been investigated by one of us experimentally without obtaining the desired result. Nevertheless, the idea of a synthetic formation of B-oxybutyric acid in the way outlined is much more probable than the assumption that the acid is a product of disassimilation of atom complexes containing many atoms of carbon.

According to our view, as already stated, this synthesis could occur either with fragments of the proteids or of the fats that contain few atoms of carbon. It is an altogether one-sided view to consider only the fats or only the proteids in this connection as some authors do. The phenomenon of acetonuria with its many modifications becomes quite comprehensible if we adhere to the views that have just been developed and assume that acetone is a synthetic product derived from certain bodies that contain few carbon atoms and that may be derived from different sources.

Normally the fragments of the proteid and fat molecules that contain few carbon atoms undergo further oxidation but only as has been repeatedly emphasized if a sufficient quantity of carbo-hydrate is present. This is probably due to the fact that the carbohydrates contain so much oxygen. A portion of this oxygen is presumably liberated when the carbohydrates undergo metabolism and is used for the oxidation processes. That the effect of the oxygen must be of a peculiar kind is demonstrated by the fact that there is no lack of respiratory oxygen in diabetes (this has been demonstrated by respiration experiments in diabetic subjects by Voit and Pettenkofer , Wein traud and Laves, etc.) One might imagine that the influence of the carbohydrates is a contact effect, exercised by the oxygen in statu nascendi that is liberated within the cell.