{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:43:21Z","timestamp":1777873401577,"version":"3.51.4"},"reference-count":43,"publisher":"Frontiers Media SA","issue":"3","license":[{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:p>\n                    We postulate that 10-formyl-7,8-dihydrofolate (10-HCO-H\n                    <jats:sub>2<\/jats:sub>\n                    folate), not 10-formyl-5,6,7,8-tetrahydrofolate (10-HCO-H\n                    <jats:sub>4<\/jats:sub>\n                    folate), is the predominant in vivo substrate for mammalian aminoimidazolecarboxamide ribotide (AICAR) transformylase, an enzyme in purine nucleotide biosynthesis de novo, which introduces carbon 2 (C\n                    <jats:sub>2<\/jats:sub>\n                    ) into the purine ring. 10-HCO-H\n                    <jats:sub>2<\/jats:sub>\n                    folate exists in vivo as labeled 10-formyl-folic acid (10-HCO-folic acid: an oxidation product of 10-HCO-H\n                    <jats:sub>4<\/jats:sub>\n                    folate and 10-HCO-H\n                    <jats:sub>2<\/jats:sub>\n                    folate) and is found after doses of labeled folic acid in humans or laboratory animals. The bioactivity of the unnatural isomer, [6 R]-5-formyltetrahydrofolate, in humans is explained by its in vivo conversion to 10-HCO-H\n                    <jats:sub>2<\/jats:sub>\n                    folate. The structure and active site of AICAR transformylase are not consistent with other enzymes that utilize 10-HCO-H\n                    <jats:sub>4<\/jats:sub>\n                    folate. Because 10-HCO-H\n                    <jats:sub>4<\/jats:sub>\n                    folate is rapidly oxidized in vitro to 10-HCO-H\n                    <jats:sub>2<\/jats:sub>\n                    folate by cytochrome C alone and in mitochondria, it is hypothesized that this process takes place in vivo. In vitro data indicate that 10-HCO-H\n                    <jats:sub>2<\/jats:sub>\n                    folate is kinetically preferred over 10-HCO-H\n                    <jats:sub>4<\/jats:sub>\n                    folate by AICAR transformylase and that this enzyme may not have access to sufficient supplies of 10-HCO-H\n                    <jats:sub>4<\/jats:sub>\n                    folate. Methotrexate blockage of the AICAR transformylase process in patients with rheumatoid arthritis suggests that dihydrofolate (H\n                    <jats:sub>2<\/jats:sub>\n                    folate) reductase is involved and is consistent with H\n                    <jats:sub>2<\/jats:sub>\n                    folate and 10-HCO-H\n                    <jats:sub>2<\/jats:sub>\n                    folate being the product and substrate for AICAR transformylase. The labeling of purine C\n                    <jats:sub>2<\/jats:sub>\n                    by an oral dose of [6 RS]-5-H[\n                    <jats:sup>13<\/jats:sup>\n                    C]O-H\n                    <jats:sub>4<\/jats:sub>\n                    folate in a human subject is consistent with 10-H[\n                    <jats:sup>13<\/jats:sup>\n                    C]O-H\n                    <jats:sub>2<\/jats:sub>\n                    folate formation from unnatural isomer, [6 R]-5-H[\n                    <jats:sup>13<\/jats:sup>\n                    C]O-H\n                    <jats:sub>4<\/jats:sub>\n                    folate, and it being a substrate for AICAR transformylase. In vitro exchange reactions of purine C\n                    <jats:sub>2<\/jats:sub>\n                    using H\n                    <jats:sub>4<\/jats:sub>\n                    folate coenzymes are not duplicated in vivo and is consistent with H\n                    <jats:sub>2<\/jats:sub>\n                    folate coenzymes being used in vivo by AICAR transformylase.\n                  <\/jats:p>","DOI":"10.1258\/ebm.2009.009151","type":"journal-article","created":{"date-parts":[[2010,5,28]],"date-time":"2010-05-28T12:59:36Z","timestamp":1275051576000},"page":"271-277","source":"Crossref","is-referenced-by-count":9,"title":["Evidence for the hypothesis that 10-formyldihydrofolate is the\n                    <i>in vivo<\/i>\n                    substrate for aminoimidazolecarboxamide ribotide transformylase"],"prefix":"10.3389","volume":"235","author":[{"given":"Joseph E","family":"Baggott","sequence":"first","affiliation":[{"name":"Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsunenobu","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2010,3,1]]},"reference":[{"key":"bibr-EBM-0905-MR-151C1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.22.10123"},{"key":"bibr-EBM-0905-MR-151C2","first-page":"853","volume-title":"Biochemistry","author":"Garrett RH","year":"2005","edition":"3"},{"key":"bibr-EBM-0905-MR-151C3","first-page":"108","volume":"334","author":"Jaenicke L","year":"1961","journal-title":"Biochem Zeitsch"},{"key":"bibr-EBM-0905-MR-151C4","doi-asserted-by":"publisher","DOI":"10.1042\/bj0720707"},{"key":"bibr-EBM-0905-MR-151C5","first-page":"191","volume-title":"Folates and Pterins","volume":"1","author":"Blakley 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