Detection and quantification of 10-formyltetrahydrofolate dehydrogenase (10-FTHFDH) in rat retina, optic nerve, and brain.
Methanol poisoning is characterized by the accumulation of formic acid, a metabolite of methanol, which can lead to metabolic acidosis and ocular toxicity. Formate metabolism to CO2 is governed by tissue H4folate and 10-FTHFDH levels. Presumably, rats are not normally susceptible to formate toxicity because they possess high hepatic H4folate and 10-FTHFDH levels. However, the ability of target tissues to metabolize formate is not known. Therefore, studies were performed to determine whether 10-FTHFDH was present in rat retina, optic nerve, and brain. 10-FTHFDH levels were determined using Western blot analysis of mitochondrial and postmitochondrial preparations from these tissues. Hepatic mitochondrial and postmitochondrial levels of 10-FTHFDH were 13 and 12 ng/micrograms protein, respectively. Postmitochondrial levels of 10-FTHFDH in rat retina, optic nerve and whole brain were 0.2, 1.3, and 2.1 ng/micrograms protein; mitochondrial values in retina and brain were 0.2 and 1.5 ng/micrograms protein, respectively. Postmitochondrial values obtained for rat brain regions were similar to those found for whole brain. These results suggest that, in rats, target tissues possess the capacity to metabolize formate to CO2 and may be protected from formate toxicity through this folate-dependent system.
Neymeyer
V R
VR
Department of Pharmacology, University of Iowa, Iowa City 52242.
Tephly
T R
TR
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology*; D005561:Formates / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D009900:Optic Nerve / Q000201:enzymology*; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000201:enzymology*; D000099295:Formyltetrahydrofolate Dehydrogenase
D005561:Formates; D000587:Oxidoreductases Acting on CH-NH Group Donors; D000099295:Formyltetrahydrofolate Dehydrogenase