[Free amino acids and activities of folate-derivative converting enzymes in nervous system of rats administered with beta, beta'-iminodipropionitrile].
Swelling of proximal axon is a morphological similarity between patients with amyotrophic lateral sclerosis (ALS) and beta, beta'-iminodipropionitrile (IDPN)-injected animals. In order to investigate whether these two states have something in common biochemically with each other, we measured free amino acids (FAAs) and activities of folate-derivative converting enzymes which participate in the metabolic turnover of the folate cycle. Thirty male Wistar rats weighing about 125 g were administered intraperitoneally with 2 g/kg of IDPN. These rats and 10 control rats injected with physiological saline were sacrificed 1, 3 and 6 weeks after injection. Subsequently organs were immediately removed and stored at -80 degrees C until analyzed. FAAs were quantitated by a JLC-6AH amino acid analyzer, and activities of the enzymes were measured by established methods. Changes in FAAs were detected not only in the central and peripheral nervous systems, but also in the other tissues examined, suggesting diverse action of IDPN. Among the various changes, elevation of taurine content in the cerebrum and spinal cord seems to be important, because the same alteration has been reported in the central nervous system (CNS) of ALS patients. In relation to the increase in taurine, metabolic slowing-down of the folate cycle which has been reported in ALS was suggested from reduced activity of N5,N10-methylenetetrahydrofolate reductase (MTR), one of the three enzymes of this metabolic cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
Takanashi
T
T
First Department of Internal Medicine, Kyorin University School of Medicine.
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D000818:Animals; D005492:Folic Acid / Q000378:metabolism*; D012696:Glycine Hydroxymethyltransferase / Q000378:metabolism*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009420:Nervous System / Q000187:drug effects* / Q000378:metabolism; D009570:Nitriles / Q000633:toxicity*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D009570:Nitriles; C008110:3,3'-iminodipropionitrile; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D012696:Glycine Hydroxymethyltransferase