ROUND TABLE DISCUSSION Bu) 
It therefore clearly appeared that, in this case, the animal was not synthesizing glycine at a suffi- 
ciently rapid rate to overcome the toxic effects of benzoate, and that a supplementary source of 
glycine in the diet was necessary for this purpose. 
Returning now to salicylate, one of the principal excretion products of salicylate is salicyluric 
acid, which is a combination of salicylic acid and glycine in amide linkage. Could it be possible 
that we will encounter a detoxification phenomenon here comparable to the benzoate situation? 
Such a study will be undertaken shortly. 
Roserts: I would just like to say that both Dr. MILLER and I feel that the contributions that 
Dr. Wrn1tTz has made, and is on the brink of making, really augur well for the future of nutritional 
science. It is again going to become an exciting frontier of biochemical endeavor. For many 
years the young people who were going into biochemistry were shying away from nutrition, and 
I think rightfully so, because much of the work had gotten into the hands of people who were 
just varying this or that constituent of a poorly defined diet and observing weight changes and 
other gross changes of that sort. But it is obvious that nutritional biochemistry is becoming an 
exciting field again. 
Winitz: Thank you very much for those very generous remarks. I think I should point out 
that when Dr. JESSE GREENSTEIN and I entered this area some six years ago, we entered it not as 
nutritionists but as chemists. I think it is important to remember, also, that the really wonderful 
and exciting early quantitative work with chemically defined diets in nutrition began with 
Rose, and Roser too viewed this area essentially as a chemist, not as a nutritionist. I myself 
have no doubt that through the use of chemically defined diets, the animal can be used essentially 
as an animated test tube which can be titrated with various chemical agents and made to respond 
in a quite predictable and reproducible manner. Such an approach will permit the study of a 
specific enzyme system or metabolic process in association with the tremendous amount of other 
metabolic activity that takes place in its natural environment—the whole animal. I really feel 
that this is much more meaningful than isolating a particular enzyme from a given tissue, putting 
it in a test tube, and then attempting to find out what it does. 
E. RoBerts: Without the iz vitvo work one wouldn’t know that benzoate inhibits D-amino acid 
oxidase. 
Wrnitz: That is certainly very true. I don’t mean to underestimate the importance of im vitro 
studies, but it should also be born in mind that when enzyme systems are studied in an artificial 
environment which bears no relation to their natural surroundings, then a distorted picture of 
the situation as it actually occurs is quite likely to emerge. For example, if the relative rates of 
oxidation of various D-amino acids by D-amino acid oxidase, as measured in the test tube, are 
compared with the relative rates of utilization of these same D-amino acids for purposes of growth, 
then an entirely different pattern becomes evident. The orders of oxidation im vivo and in vitvo 
are very dissimilar, with some of the amino acids, that are very poorly utilized by the animals 
being very rapidly oxidized in the test tube, and vice versa. 
In the case of isoleucine, for example, D-alloisoleucine which is quite effectively oxidized im 
vityo will not support growth if it replaces an equimolar amount of L-isoleucine in the diet, whereas 
b-tryptophane, which is more slowly oxidized in vityo is utilized in vivo to an appreciable extent. 
So it becomes a matter of studying renal reabsorption mechanisms and we find that when pb- 
alloisoleucine is provided in the diet, it subsequently appears in appreciable quantities in the 
urine, whereas D-tryptophane does not. The way to make p-alloisoleucine utilizable for purposes 
of growth—and this we have done—is to provide it in the diet in very high excess, so that although 
the major portion of it is rapidly excreted into the urine unchanged, sufficient material is never- 
theless available to permit it to be utilized in part. What we have done here is to overload the 
renal mechanism for disposing of this amino acid, so that a portion of it is recycled and even- 
tually oxidized. 
SCHREIER: May I now ask Dr. WitTER to present some of his studies on amino acids in the brain. 
Witter: I would like to take this opportunity to present the results of some studies that 
Dr. Farrior and I have carried out on the effect of DDT and dieldrin on the free amino acids of the 
rat brain. 
Previous workers have investigated the effects of a variety of drugs on the free amino acids 
in the central nervous system. Most of these studies have been summarized in the first symposium 
on amino acids which was held here a few years ago!. However, no report has appeared on the 
effects of chlorinated hydrocarbon insecticides on the free amino acids of the mammalian brain. 
This is somewhat surprising, in view of the widespread use of these compounds and their known 
effects on the nervous system. 
Accordingly, a study was made of the effects of two members of the group of chlorinated 
hydrocarbon insecticides on the free amino acids of rat brain. The compounds studied were 
DDT and dieldrin. Both of these compounds are stimulants of the central nervous system, but 
peripheral stimulation may play a role to an unknown degree in the pharmacological effects of 
these compounds. 
References p. 524 
