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Adenylic Acid in Nutrition
The Medical Clinics of North America March,1943
ADENYLIC ACID IN NUTRITION WILLIAM BENNETT BEAN, M.O.·
ADENYLIC acid occurs in certain animal and plant tissues. It is a constituent of many substances such as yeast and crude liver extracts which are rich in vitamins of the B complex. Since it is not known that adenylic acid is a vitamin, that is, a substance which must be supplied preformed in food, it is discussed here on clinical grounds only. Tests for adenylic acid are not satisfactory for studying its fate after ingestion or injection. Although there is no proof that a deficiency occurs when the diet contains little adenylic acid; certain symptoms occurring in persons with nutritional deficiencies respond to its administration. The normal concentration in blood and tissues is higher than that of most accepted vitamins. Three facts suggest that it may have a fundamental role in the economy of mammalian metabolism. 1. As a precursor of cophosphorylase (adenyl pyrophosphate) and a component of many polynucleotides which have known functions in enzyme-coenzyme systems containing riboflavin, niacin amide and several oxidases, it is essential in certain phases of cellular respiration. 2. When yeast or muscle adenylic acid is administered intravenously to human subjects several reactions occur. A deep involuntary sigh, a feeling of smothering, and a sense of imminent dissolution follow the rapid injection of a few milligrams, an effect similar to that produced by cyanide. Transitory flushing of the skin appears next, sometimes accompanied by generalized tingling, abdominal cramps and headache. Tachycardia often develops. The electrocardiogram .. Assistant Professor of Internal Medicine, University of Cincinnati College of Medicine; Assisting Visiting Physician, Cincinnati General Hospital (Cincinnati, Ohio). (On leave of absence. Now Captain, Armored Force, Medical Research Laboratory, Army of the United States, Ft. Knox, Kentucky.) 483
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WILLIAM BENNETI BEAN
may show prolongation of the P-R and Q-T intervals, T wave flattening or inversion, and P wave changes. The reaction which follows the administration of nicotinic acid is another example of pharmacological effects caused by compounds with vitamin activity. These reactions merit further study. . 3. Muscle or yeast adenylic acid causes improvement in a painful, recurring ulcer of the mouth and tongue which occurs in a number of ill-nourished persons with pellagra, beriberi, ariboflavinosis or subclinical vitamin B-complex deficiencies, and in a few instances it has relieved a thiaminerefractory neuritis. The simultaneous return of the sense of health and well-being may have been the result of freedom from distressing pain. One needs no stronger tribute to the therapeutic excellence of this remedy than to observe the patient's desire for the injection, once it has brought relief, unpleasant and alarming as it is. Although we have seen no serious result following the administration of adenylic acid, the severe reaction it causes makes its routine use inadvisable. In our experience a satisfactory response has not been observed in identical appearing ulcers in well-nourished persons. The status of adenylic acid is thus unsettled. Proof that it is a vitamin is wanting but its value in treating a specific disorder associated with vitamin deficiencies has been shown. This virtue may be properly pharmacologic and not the restitution of a specific substance of which the tissues are depleted. Therefore, until our knowledge concerning adenylic acid is more complete, we must assign it to that indeterminate therapeutic terrain bounded upon one side by known vitamins and elsewhere by the several classes of therapeutic agents. BIBLIOGRAPHY
1. Spies, T. D., Bean, W. B. and Vilter, R. W.: Adenylic Acid in Human
Nutrition. Ann. Int. Med., 13:1616, 1940. 2. Vilter, R. W., Bean, W. B. and Spies, T. D.: The Effect of Yeast and Muscle Adenylic Acid in Malnourished Persons with Pellagra and Peripheral Neuritis. J. Lab. Clin. Med., 27:527, 1942.
ADENYLIC ACID IN NUTRITION WILLIAM BENNETT BEAN, M.O.·
ADENYLIC acid occurs in certain animal and plant tissues. It is a constituent of many substances such as yeast and crude liver extracts which are rich in vitamins of the B complex. Since it is not known that adenylic acid is a vitamin, that is, a substance which must be supplied preformed in food, it is discussed here on clinical grounds only. Tests for adenylic acid are not satisfactory for studying its fate after ingestion or injection. Although there is no proof that a deficiency occurs when the diet contains little adenylic acid; certain symptoms occurring in persons with nutritional deficiencies respond to its administration. The normal concentration in blood and tissues is higher than that of most accepted vitamins. Three facts suggest that it may have a fundamental role in the economy of mammalian metabolism. 1. As a precursor of cophosphorylase (adenyl pyrophosphate) and a component of many polynucleotides which have known functions in enzyme-coenzyme systems containing riboflavin, niacin amide and several oxidases, it is essential in certain phases of cellular respiration. 2. When yeast or muscle adenylic acid is administered intravenously to human subjects several reactions occur. A deep involuntary sigh, a feeling of smothering, and a sense of imminent dissolution follow the rapid injection of a few milligrams, an effect similar to that produced by cyanide. Transitory flushing of the skin appears next, sometimes accompanied by generalized tingling, abdominal cramps and headache. Tachycardia often develops. The electrocardiogram .. Assistant Professor of Internal Medicine, University of Cincinnati College of Medicine; Assisting Visiting Physician, Cincinnati General Hospital (Cincinnati, Ohio). (On leave of absence. Now Captain, Armored Force, Medical Research Laboratory, Army of the United States, Ft. Knox, Kentucky.) 483
484
WILLIAM BENNETI BEAN
may show prolongation of the P-R and Q-T intervals, T wave flattening or inversion, and P wave changes. The reaction which follows the administration of nicotinic acid is another example of pharmacological effects caused by compounds with vitamin activity. These reactions merit further study. . 3. Muscle or yeast adenylic acid causes improvement in a painful, recurring ulcer of the mouth and tongue which occurs in a number of ill-nourished persons with pellagra, beriberi, ariboflavinosis or subclinical vitamin B-complex deficiencies, and in a few instances it has relieved a thiaminerefractory neuritis. The simultaneous return of the sense of health and well-being may have been the result of freedom from distressing pain. One needs no stronger tribute to the therapeutic excellence of this remedy than to observe the patient's desire for the injection, once it has brought relief, unpleasant and alarming as it is. Although we have seen no serious result following the administration of adenylic acid, the severe reaction it causes makes its routine use inadvisable. In our experience a satisfactory response has not been observed in identical appearing ulcers in well-nourished persons. The status of adenylic acid is thus unsettled. Proof that it is a vitamin is wanting but its value in treating a specific disorder associated with vitamin deficiencies has been shown. This virtue may be properly pharmacologic and not the restitution of a specific substance of which the tissues are depleted. Therefore, until our knowledge concerning adenylic acid is more complete, we must assign it to that indeterminate therapeutic terrain bounded upon one side by known vitamins and elsewhere by the several classes of therapeutic agents. BIBLIOGRAPHY
1. Spies, T. D., Bean, W. B. and Vilter, R. W.: Adenylic Acid in Human
Nutrition. Ann. Int. Med., 13:1616, 1940. 2. Vilter, R. W., Bean, W. B. and Spies, T. D.: The Effect of Yeast and Muscle Adenylic Acid in Malnourished Persons with Pellagra and Peripheral Neuritis. J. Lab. Clin. Med., 27:527, 1942.