138 BIOCHIMICA ET BIOPHYSICA ACTA VOL. 4 (1950) 



GLYCOLYSIS IN PHARMACOLOGY^' ^ 



by 



CHALMERS L. GEMMILL 



Department of Pharmacology, Medical School, University of Virginia, 

 Charlottesville, Virginia [U.S.A.) 



Classical pharmacology deals with the action of drugs on organ systems. If the 

 question is raised as to why a certain drug acts on a particular organ system, the answer 

 may only be obtained by searching for some system inside the cell which is sensitive 

 to the drug in question. The most fruitful line of endeavor has been to test the affect 

 of the drug on enzyme systems known to be involved in cellular metabolism. Many 

 pharmacological actions of drugs can be explained in this manner. For example, the 

 pharmacological properties of vitamins, physostigmine, BAL, and cyanide have been 

 explained to everyone's satisfaction on an enzymatic basis. During the past war, a great 

 deal of attention was paid to the action of antimalarial drugs, ionizing radiation and 

 chemical warfare agents on enzymatic processes. In fact, there is a growing school in 

 Pharmacology which has for its main purpose the localization of drug action on en- 

 zymatic processes. Some of this work has been reviewed by Green^, Bernheim^, Clark^, 

 and McElroy*. The recent book by Work and Work^ is an excellent example of the 

 development of this field in chemotherapy. 



Welch and Bueding^ have laid down very severe criteria which should be met 

 before the action of a drug can be attributed to its effects on an enzyme system. These 

 criteria involve concentrations, organ and tissue specificity and close parallelism be- 

 tween the activity of structurally related compounds. These criteria are very hard to 

 meet in this field. It is very difficult to determine how much drug is acting on a specific 

 organ when the drug is administered to the whole animal. When working on enzyme 

 systems, cell interfaces are destroyed and permeability is no longer a question, which 

 may modify drug action. Therefore, the criteria of Welch and Bueding^ should be 

 used as an ultimate goal and not be used to delay or to give up work and thinking in 

 this field. 



It is the purpose of this article to give several examples of drug action on the gly- 

 colytic system in order to show how the discoveries of Meyerhof are now being used 

 in Pharmacology. Meyerhof^ used many pharmacological agents as chemical tools in 

 his work on muscle metabolism. Narcotics, methylene blue, chloroform, caffeine, and 

 moniodoacetic acid are a few of many agents employed in his work. More recently 

 Meyerhof and his associates have employed alloxan^ in their study of glycolysis of 

 brain preparations and have reported^ the effects of potassium i, 2-naphthoquinone-4- 

 sulfonate on the respiration and glycolysis of Trypanosoma equiperdum. 



^ Read before a Seminar at the Army Chemical Center, March 9, 1949. 



2 In this paper, the term "glycolysis" is used in the general meaning for the break down of 

 any carbohydrate into lactic acid by enzymatic processes. 



References p. 142 j 143. 



