Some Aspects of Citric Acid Metabolism*

In addition to its presence in milk (9) and urine (1) citric acid has, within the past few years, been found in many other body fluids including sweat (12), cerebrospinal fluid (2), aqueous humor (7), follicular fluid (14), and blood (3). Apparently, saliva is the only body fluid tested in which citrate has not been detected.l Although citric acid appears to be so generally distributed and is excreted by the normal individual in amounts from 0.2 to 1.0 gm. daily (15), its role in metabolism is obscure. Tolerance studies have led to confusing results because of the interfering action of the large amounts of alkali present in the citrates used (sodium citrate contains practically as much alkali per gm. as sodium bicarbonate). The fact that citric acid forms a soluble, slightly ionized salt with calcium has suggested that it may be related to calcium metabolism (5), but Greenberg and Greenberg (6) find little good evidence that such a slightly ionized combination is present in the blood. In 1931, ostberg (15), on the basis of evidence which showed that the amount of citric acid excreted varies directly with the pH of the urine, suggested that citric acid is primarily a part of the acid-base regulatory mechanism and that it is synthesized to neutralize excess alkali just as ammonia is synthesized to neutralize excess acid. On the other hand, the large amounts of citrate excreted in fasting and on ketogenic diets (4) indicate that citrate metabolism must be controlled by other factors in addition to acid-base relationships. In the present work, the influence of acid-base relationships and