AGENTS ON AMINO ACIDS IN MAMMALIAN BRAIN 501 
scope to a consideration of the effects of four potential vitamin B, antimetabolites 
upon amino acid levels and some related enzyme systems. 
Almost every amino acid at some point of its metabolism undergoes transforma- 
tions which are catalyzed by enzymes that require pyridoxal phosphate (PyP) as 
a cofactor. It is well known that 7 vivo some vitamin B,-requiring enzymes are 
more sensitive to B, antimetabolites than others. The biochemical effects of 4- 
methoxymethylpyridoxine, administered to mice, have been studied?. The only 
significant change observed in brain tissue was a decrease in the concentration of 
y-aminobutyric acid (GABA)?. In cats the injection of 4-methoxymethylpyridoxine 
affected amino acid levels in brain tissue by decreasing the level of GABA and in- 
creasing the level of glutamine?. 4-Methoxymethylpyridoxine affected the concentra- 
tion of a number of amino acids in the brains of rats (Figs. 1-4). Levels of GABA, 
alanine and ethanolamine phosphate were decreased as the result of methoxypyri- 
doxine administration. Glycine and taurine decreased to a lesser extent and glutamine, 
glutathione, serine, glutamic and aspartic acids appeared unchanged. It is possible 
that the levels of some other amino acids which were not detected in these chromato- 
grams also were changed as a result of the vitamin B, antagonist?. 
Thiosemicarbazide, a carbonyl-trapping agent, is more limited in its effect. Early 
results with this compound were interpreted as showing that a specific inhibition of 
glutamic acid decarboxylase (GAD) in brain was produced®. Later results indicated 
that pyridoxal kinase, the enzyme which catalyzes the synthesis of PyP from pyri- 
LABLE 
EFFECT OF PYRIDOXAL INJECTIONS UPON GABA LEVELS IN BRAINS 
OF THIOSEMICARBAZIDE-TREATED RATS* 

TSC Pyridoxal 
Alias Ateas Cortex Cerebellum Collicult Diencephalon 
(min) (h) 
= = 24§ (23-24) 27 (26-29) BO (45—55) 6r (55-65) 
95 == 17 (16-18) 20 (18-23) 31 (30-33) 43 (42-44) 
85 1/488 20 (20-21) 25 25527) Se) eye) 50 (47-53) 
85 I LO (L513) 230 (22-25) 40 (39-42) 40 (39-40) 
85 2 ES (3-14) LON (7-20) 33 (32-34) 35: (83-37) 
85 3 17 (16-19) 22 (2122) 37. (34-39) 38 (37-38) 
85 5 imei (e710) 2B (22—25) 43 (42-44) 38 (37-40) 
85 7 20 (19-22) Dein (2227) 47 (41-53) 50 (36-62) 
* This experiment has been repeated twice (to 2h after pyridoxal administration) with 
rats of different age and sex. In both trials each time period was represented by two animals. 
Results were in agreement with those shown for the trial recorded in Table I. 
** A t, time period between the injection of TSC intraperitoneally (20 mg/kg, pH 8) and the 
time at which the animal was either decapitated or pyridoxal was injected. 
*** /\ t, time period between the injection of pyridoxal HCl (50 mg/kg, pH 4.5) and the time 
at which the animal was decapitated. 
§ The method for sampling and assay of brain areas for GABA has been described!?. Above 
data are based upon one trial with two or three fed Sprague Dawley female rats (200 + 15 g wt.) 
per point. Vatiability among animals in levels of GABA in corresponding brain areas is indicated. 
§§ The administration of pyridoxal to thiosemicarbazide-treated rats appeared to produce a slight 
transient elevation of GABA levels at 15 min after intraperitoneal injection of the vitamin. The 
significance of this elevation, if any, remains to be evaluated. 
References p. 508 
