{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:57:51Z","timestamp":1792677471318,"version":"4.5.0"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,9,26]]},"abstract":"<jats:p>\n                    Local rates of cerebral protein synthesis\n (lCPS\n                    <jats:sub>leu<\/jats:sub>\n                    ) were measured with the quantitative\n autoradiographic [1-\n                    <jats:sup>14<\/jats:sup>\n                    C]leucine method in a genetic mouse\n model (\n                    <jats:italic>Pah<\/jats:italic>\n                    <jats:sup>enu2<\/jats:sup>\n                    ) of phenylketonuria. As in\n the human disease,\n                    <jats:italic>Pah<\/jats:italic>\n                    <jats:sup>enu2<\/jats:sup>\n                    mice have a\n mutation in the gene for phenylalanine hydroxylase. We compared adult\n homozygous (HMZ) and heterozygous (HTZ)\n                    <jats:italic>Pah<\/jats:italic>\n                    <jats:sup>enu2<\/jats:sup>\n                    mice with the background strain\n (BTBR). Arterial plasma concentrations of phenylalanine (Phe) were\n elevated in both HMZ and HTZ mutants by 21 times and 38%,\n respectively. In the total acid-soluble pool in brain concentrations of\n Phe were higher and other neutral amino acids lower in HMZ mice\n compared with either HTZ or BTBR mice indicating a partial saturation\n of the\n                    <jats:sc>l<\/jats:sc>\n                    -amino acid carrier at the blood brain barrier by\n the elevated plasma Phe concentrations. In a series of steady-state\n experiments, the contribution of leucine from the arterial plasma to\n the tRNA-bound pool in brain was found to be statistically\n significantly reduced in HMZ mice compared with the other groups,\n indicating that a greater fraction of leucine in the precursor pool for\n protein synthesis is derived from protein degradation. We found\n reductions in lCPS\n                    <jats:sub>leu<\/jats:sub>\n                    of about 20% throughout the brain in\n the HMZ mice compared with the other two groups, but no reductions in\n brain concentrations of tRNA-bound neutral amino acids. Our results in\n the mouse model suggest that in untreated phenylketonuria in adults,\n the partial saturation of the\n                    <jats:sc>l<\/jats:sc>\n                    -amino acid transporter at\n the blood\u2013brain barrier may not underlie a reduction in cerebral\n protein synthesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.20.11014","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"11014-11019","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":65,"title":["Cerebral protein synthesis in a genetic mouse model of phenylketonuria"],"prefix":"10.1073","volume":"97","author":[{"given":"Carolyn Beebe","family":"Smith","sequence":"first","affiliation":[{"name":"Laboratory of Cerebral Metabolism, National Institute of Mental\r Health, United States Public Health Service, Department of Health and\r Human Services, Bethesda, MD 20892-4030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Kang","sequence":"additional","affiliation":[{"name":"Laboratory of Cerebral Metabolism, National Institute of Mental\r Health, United States Public Health Service, Department of Health and\r Human Services, Bethesda, MD 20892-4030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,9,26]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"495","volume-title":"The Metabolic Basis of Inherited Disease","author":"Scriver C R","year":"1989","unstructured":"C R Scriver, S Kaufman, S L C Woo The Metabolic Basis of Inherited Disease, eds C R Scriver, A L Beaudet, W S Sly, D Valle (McGraw\u2013Hill, New York), pp. 495\u2013546 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