Sidney Weinhouse and the Mechanism of Ketone Body Synthesis from Fatty Acids
Year: 2005
Type: article
Abstract: Fatty Acid Metabolism. The Mechanism of Ketone Body Synthesis from Fatty Acids, with Isotopic Carbon as Tracer (Weinhouse, S., Medes, G., and Floyd, N. F. (1944) J. Biol. Chem. 155, 143-151) Sidney Weinhouse (1909-2001) was born and educated in Chicago. He received both his B.S. (1933) and his Ph.D. (1936) from the University of Chicago and then remained at the University to do his postdoctoral work. He moved to Philadelphia in the early 1940s where he joined the staff of the Lankenau Hospital Research Institute, with a joint faculty appointment at Temple University. He was one of an early group of biochemists who pioneered the use of isotopes in metabolic studies. Isotopes became generally available after World War II, but compounds of biological interest, such as fatty acids, had to be synthesized. Weinhouse developed a cordial relationship with the owner of Sun Oil Corp. in Philadelphia, who strongly supported the future of biochemical research. He gave Weinhouse and his colleagues access to the large scale columns needed to isolate the 13CO2 that was used for the chemical synthesis of fatty acids, which are the subject of the Journal of Biological Chemistry (JBC) Classic reprinted here. This story starts with the work of Franz Knoop (1Knoop F. Der Abbau aromatischerFettsäuren im Tierkörper..Beitr. Chem. Physiol.Pathol. 1904; 6: 150-162Google Scholar), who in 1904 demonstrated that when phenyl derivatives of even-chain fatty acids were fed to dogs, the product found in their urine was phenylacetate. The scheme proposed by Knoop was termed the β-oxidation theory and was later verified by H. D. Dakin (2Dakin H.D. The mode of oxidation in theanimal organism of phenyl derivatives of fatty acids. Part V. Studies on thefate of phenylvaleric acid and its derivatives..J. Biol.Chem. 1909; 6: 221-233Abstract Full Text PDF Google Scholar), who published a similar finding in the JBC in 1909 and was the subject of a previous JBC Classic (3Classic JBC Dakin H.D. J. Biol.Chem. 1908; 4 (http://www.jbc.org/cgi/content/full/277/15/e4): 419-435Abstract Full Text PDF Google Scholar). This work led to the proposal by Gustav Embden that ketone bodies arise from the last four carbons that are generated during β-oxidation of an even-chain fatty acid. In contrast, Eaton M. McKay and colleagues (4MacKay E.M. Barnes R.H. Carne H.O. Wick A.N. Ketogenic activity of acetic acid..J. Biol.Chem. 1940; 135: 157-163Abstract Full Text PDF Google Scholar) proposed that two molecules of acetate, which were produced by the β-oxidation of fatty acids, condensed to form acetoacetic acid. Thus, when Weinhouse began his studies of fatty acid oxidation, there were two possible mechanisms suggested for the formation of ketone bodies by the liver. In their JBC Classic paper, Weinhouse, together with Grace Medes and Norman F. Floyd, incubated liver slices from 24-h fasted rats with [13C]carboxyl-labeled octanoic acid. The acetoacetate generated was isolated and degraded, and the 13C in the carboxyl and carbonyl carbon atoms was determined using a mass spectrometer. They found that the 13C content of the carbonyl and carboxyl carbons of the newly formed acetoacetate were equal, as would be predicted by the β-oxidation-condensation hypothesis. With the subsequent discovery of acetyl-CoA by Lipmann in 1947, which was the subject of a previous JBC Classic (5Classic JBC Lipmann F. J. Biol.Chem. 1945; 160 (http://www.jbc.org/cgi/content/full/280/21/e18): 173-190Abstract Full Text PDF Google Scholar), the pathway of ketone body synthesis was formally elucidated by 1950. Sidney Weinhouse served as Chair of the Division of Biochemistry at the Institute for Cancer Research at Fox Chase and as Director of the Fels Research Institute at Temple University Medical School. During these years, he made significant contributions in the area of isoenzyme expression in cancer tissue and glucokinase. Weinhouse received many honors and awards throughout his career, including the American Association for Cancer Research's Clowes Memorial Award (1972). He was elected to the National Academy of Sciences in 1979. In addition to having a productive research career, Weinhouse was active in several other aspects of science. He served three 4-year terms and two ex officio terms on the Board of Directors of the American Association for Cancer Research between 1957 and 1984 and was president of the Association from 1981 to 1982. Weinhouse also served as editor of Cancer Research from 1969 through 1979. During that time he doubled the size of the Editorial Board in order to ensure thorough and equitable review of submitted papers. He also expanded the journal from 2500 pages to more than 5300 pages per year. When his term as Editor was over, Weinhouse served as Associate Editor from 1980 to 1987 and as Cover Editor from 1986 to 1999. He also served two terms as a member of the Editorial Board of the JBC. 1All biographical information on Sidney Weinhouse was taken from Ref. 6Litwack G. Baserga R. Foti M. Inmemoriam: Sidney Weinhouse..Cancer Res. 2001; 61: 8930-8931Google Scholar. 1All biographical information on Sidney Weinhouse was taken from Ref. 6Litwack G. Baserga R. Foti M. Inmemoriam: Sidney Weinhouse..Cancer Res. 2001; 61: 8930-8931Google Scholar.
Source: Journal of Biological Chemistry
Language: English
Subfield: History and Philosophy of Science
Field: Arts and Humanities
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1948053489