Biochemistry, 4th Edition P80. Continuing Garrett and Grisham's innovative conceptual and organizing framework, "Essential Questions," BIOCHEMISTRY guides students through course concepts in a way that reveals the beauty and usefulness of biochemistry in the everyday world. Streamlined for increased clarity and readability, this edition also includes new photos and illustrations that show the subject matter consistently throughout the text. New end-of-chapter problems, MCAT practice questions, and the unparalleled text/media integration with the power of CengageNOW round out this exceptional package, giving you the tools you need to both master course concepts and develop critical problem-solving skills you can draw upon. | How Is Cholesterol Synthesized 753 CRITICAL DEVELOPMENTS IN BIOCHEMISTRY The Long Search for the Route of Cholesterol Biosynthesis Heilbron Kamm and Owens suggested as early as 1926 that squalene is a precursor of cholesterol. That same year . Channon demonstrated that animals fed squalene from shark oil produced more cholesterol in their tissues. Bloch and Rittenberg showed in the 1940s that a significant amount of the carbon in the tetracyclic moiety and in the aliphatic side chain of cholesterol was derived from acetate. In 1934 Sir Robert Robinson suggested a scheme for the cyclization of squalene to form cholesterol before the biosynthetic link between acetate and squalene was understood. Squalene is actually a polymer of isoprene units and Bonner and Arreguin suggested in 1949 that three acetate units could join to form five-carbon isoprene units see figure a . In 1952 Konrad Bloch and Robert Langdon showed conclusively that labeled squalene is synthesized rapidly from labeled acetate and also that cholesterol is derived from squalene. Langdon a graduate student of Bloch s performed the critical experiments in Bloch s laboratory at the University of Chicago while Bloch spent the summer in Bermuda attempting to demonstrate that radio-actively labeled squalene would be converted to cholesterol in shark livers. As Bloch himself admitted All I was able to learn was that sharks of manageable length are very difficult to catch and their oily livers impossible to slice Bloch 1987 . In 1953 Bloch together with the eminent organic chemist R. B. Woodward proposed a new scheme see figure b for the cyclization of squalene. Together with Fyodor Lynen Bloch received the Nobel Prize in Medicine or Physiology in 1964 for his work. The picture was nearly complete but one crucial question remained How could isoprene be the intermediate in the transformation of acetate into squalene In 1956 Karl Folkers and his a ch2 C c ch2 H Isoprene colleagues at Merck Sharpe Dohme .
