BIOCHEMICAL PATHWAYS: Moris Friedkin and Albert Lehninger

1. BIOCHEMICAL PATHWAYS: MorisFriedkin and Albert Lehninger By: Isabella Boushey, Camille Santos, & Ingrid Harb

2. Albert Lehninger • American biochemist born on February 17th, 1917 in Bridgeport, Connecticut. • Attended Wesleyan University as an English major • Went to the University of Wisconsin where he studied biochemistry and received his Ph.D in 1942 • Received several faculty positions at the University of Chicago and University of Wisconsin • Went to the John Hopkins University School of Medicine • Author of several classical texts such as Biochemistry, The Mitochondrion, and Bioenergetics.

3. Morris E. Friedkin • Born on December 30th, 1918 in Kansas City, Missouri. • Attended Kansas City Junior College from where he received an A.A. in chemistry • Continued his studies at Iowa State College from where he received a B.S. in chemistry and an M.S. in analytical chemistry • Enrolled in the doctorate program at the University of Chicago where he became one of the graduate students of Albert Lehninger • Received his Ph.D in 1948 • Received different faculty jobs at different places • Devoted the rest of his life to teaching and research • Research focused on folic acid metabolism, the biochemical basis of the cell cycle and cell growth, the use of radioactively labeled molecules in biochemical research, molecular pharmacology, etc..

4. Timeline • 0. Eduard Buchner and Hans Buchner – discovers cell- free fermentation • 1. Arthur Harden and William Young - in 1929, discovered ATP • 2. Gustav Embden - first to discover and link together all the steps involved in the conversion of glycogen to lactic acid • 3. Otto Meyerhof & JakubParnas – known for The most common type of glycolysis is the Embden-Meyerhof-Parnas (EMP pathway) • 4. Otto Heinrich Warburg – 1931, his research into cellular respiration showed that cancer thrives in anaerobic (without oxygen) or acidic conditions. • 5. Albert Szent-Györgyi - was the first to isolate vitamin C, and his research on biological oxidation provided the basis for Krebs' citric acid cycle • 6. Hans Adolf Kreb - 1937 Identification of citric acid cycle or "Krebs Cycle"

5. Experiments and Findings • First started working with and studying fatty acids and how they work in the body • Expanded interest to studying whole cell extracts • Aim was to isolate a specific set of enzymes that catalyzed fat metabolism • Separated the mitochondria through using dense sugar solution without damaging other organelles

6. Experiments and Findings • Set up a chilled centrifuge in a refrigerator • Found that the isolated mitochondria could break down fatty acid chains, while the remaining parts of the cell could not • The mitochondria also contained the enzymes for the citric acid cycle, as well as for the production of ATP • It could not begin the breakdown of glucose • Lehninger identified the location of nearly all the major energy reactions in the cell

7. Centrifuge

8. Experiments and Findings • Lehninger's findings became very important in cell biology • It was the first time that a specific function of a cell’s organelle had been proven • This discovery showed that all functions of the cell were separated into different organelles that could be studied individually

9. Experiments and Findings • Had been concluded that for each oxygen the cell consumes three ATP molecules are produced • Lehninger showed with the help of his student Morris Friedkin, “the suspected role of electron transport through the cytochrome system.”

10. Experiments and Findings • Deduced that ATP was produced from high energy electrons that are produced from NADH which is produced during the Kreb’s Cycle • Able to show how NADH could be produced by using β-hydroxybutyrate • He measured the oxygen consumption during this process using a classic apparatus designed by Warburg

11. Experiments and Findings • Made important conclusions on how ion concentrations affected reaction rates • Shown through the synthesis of ATP through the ETC when there is a high concentration of protons on the intermembrane space, which leads to protons diffusing from a high concentrated area to a lower concentrated area. This happens when the protons pass through the ATP synthase and trigger the reaction of the production of ATP.

12. References: • "Albert L. Lehninger." Medical Archives of The Johns Hopkins Medical Institutions. N.p., n.d. Web. 17 Oct. 2012. <http://www.medicalarchives.jhmi.edu/sgml/lehninger.html>.  • "forthcoming in New Dictionary of Scientific Biography." forthcoming in New Dictionary of Scientific Biography. N.p., n.d. Web. 17 Oct. 2012. <http://www.tc.umn.edu/~allch001/papers/lehninger.pdf>. • "Friedkin, Morris. []." SNAC. N.p., n.d. Web. 17 Oct. 2012. <http://socialarchive.iath.virginia.edu/xtf/view?docId=friedkin-morris-cr.xml>.  • "Mitochondria: A Historical Review." Mitochondria: A Historical Review. N.p., n.d. Web. 17 Oct. 2012. <http://jcb.rupress.org/content/91/3/227s.full.pdf>.  • "The ATP Requirement for Fatty Acid Oxidation: the Early Work of Albert L. Lehninger." THE JOURNAL OF BIOLOGICAL CHEMISTRY. N.p., n.d. Web. 17 Oct. 2012. <http://www.jbc.org/content/280/14/e11.full.pdf>.