Sofian Atia - October 15, 2018

Formate Metabolism

Formate is produced by the mitochondrial metabolism of a number of substrates and it is the only non-tetrahydrofolate (THF)-linked intermediate in one-carbon metabolism. The most important quantitative routes of formate production are thought to involve the production of 5,10-methylene-THF in mitochondria from two amino acids (serine and glycine), and from two intermediates in choline catabolism (sarcosine and dimethylglycine). Despite the fact that formate is largely produced in mitochondria, it is incorporated into the cytosolic folate pool where it can be used for (a) Synthesis of purine nucleotides, (b) Synthesis of thymidylate. (c) Provision of methyl groups to S adenosylmethionine (SAM) which are used in a large number of methylation reactions. Formate can be eliminated via the oxidation of the formyl group of 10-formyl-THF. This can occur in both the mitochondrion and in the cytosol. In both cases, the 10-formyl group of 10-formyl-THF has two possible metabolic fates, either oxidation to CO2 via the activity of ALDH1L2 (aldehyde dehydrogenase1 family, member L2) or release as formate by MTHFD1L (10-formyl-THF synthetase)
Experimental goals: our first experiment examined in vivo formate production in male and female rats as well as the production and catabolism of formate by isolated liver mitochondria. Second experiment examined the effect of betaine on plasma formate concentration, in vivo formate production and plasma MMA and Hcy levels. The second experiment also studied the effect of betaine on the rate of formate production from isolated liver mitochondria from four formate precursors, and effect of betaine on the rate of CO2 production from isolated liver mitochondria from 3-14C Serine in vitamin B12 deficient rats.



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