{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T03:02:44Z","timestamp":1761102164316},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1974,4,1]]},"abstract":"<jats:p>1. The effects of 2-oxo-4-methylpentanoate, 2-oxo-3-methylbutanoate and 2-oxo-3-methylpentanoate on the activity of pyruvate dehydrogenase (EC 1.2.4.1), citrate synthase (EC 4.1.3.7), acetyl-CoA carboxylase, (EC 6.4.1.2) and fatty acid synthetase derived from the brains of 14-day-old rats were investigated. 2. The pyruvate dehydrogenase enzyme activity was competitively inhibited by 2-oxo-3-methylbutanoate with respect to pyruvate with a Ki of 2.04mm but was unaffected by 2-oxo-4-methylpentanoate or 2-oxo-3-methylpentanoate. 3. The citrate synthase activity was inhibited competitively (with respect to acetyl-CoA) by 2-oxo-4-methylpentanoate (Ki~7.2mm) and 2-oxo-3-methylbutanoate (Ki~14.9mm) but not by 2-oxo-3-methylpentanoate. 4. The acetyl-CoA carboxylase activity was not inhibited significantly by any of the 2-oxo acids investigated. 5. The fatty acid synthetase activity was competitively inhibited (with respect to acetyl-CoA) by 2-oxo-4-methylpentanoate (Ki~930\u03bcm) and 2-oxo-3-methylpentanoate (Ki~3.45mm) but not by 2-oxo-3-methylbutanoate. 6. Preliminary experiments indicate that 2-oxo-4-methylpentanoate and 2-oxo-3-phenylpropionate (phenylpyruvate) significantly inhibit the ability of intact brain mitochondria from 14-day-old rats to oxidize pyruvate. 7. The results are discussed with reference to phenylketonuria and maple-syrup-urine disease. A biochemical mechanism is proposed to explain the characteristics of these diseases.<\/jats:p>","DOI":"10.1042\/bj1400025","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T19:53:43Z","timestamp":1439236423000},"page":"25-29","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Differential effects of 2-oxo acids on pyruvate utilization and fatty acid synthesis in rat brain"],"prefix":"10.1042","volume":"140","author":[{"given":"John B.","family":"Clark","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Medical College of St. Bartholomew's Hospital, University of London, Charterhouse Square, London EC1M 6BQ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Land","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical College of St. Bartholomew's Hospital, University of London, Charterhouse Square, London EC1M 6BQ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/140\/1\/25\/562133\/bj1400025.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/140\/1\/25\/562133\/bj1400025.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T15:56:01Z","timestamp":1637942161000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/140\/1\/25\/8930\/Differential-effects-of-2-oxo-acids-on-pyruvate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1974,4,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1974,4,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj1400025","relation":{},"ISSN":["0264-6021"],"issn-type":[{"value":"0264-6021","type":"print"}],"subject":[],"published":{"date-parts":[[1974,4,1]]}}}