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Wakil, Salih J. CURRICULUM VITAE NAME: Salih J. Wakil, Ph.D. PRESENT TITLE AND AFFILIATION: Distinguished Service Professor L. T. Bolin Professor Chairman Emeritus Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine CITIZENSHIP: United States MARITAL STATUS: Married with four children OFFICE ADDRESS: Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine One Baylor Plaza, BCMC 355A1 Houston, Texas 77030 Telephone: (713) 798-4783 Fax: (7l3) 796-9438 EDUCATION: 1945-1948 B.Sc. in Chemistry The American University of Beirut, Lebanon 1949-1952 Ph.D. in Biochemistry University of Washington, Seattle, Washington POSTGRADUATE TRAINING: 1949-1952 Research Fellow University of Washington, Seattle, Washington 1952-1956 Research Associate Institute for Enzyme Research University of Wisconsin, Madison, Wisconsin D:\582729855.doc 1 Wakil, Salih J. 2 FACULTY POSITIONS: 1956-1959 Assistant Professor Institute for Enzyme Research University of Wisconsin, Madison, Wisconsin 1959-1960 Assistant Professor Department of Biochemistry Duke University Medical School, Durham, North Carolina 1960-1965 Associate Professor Department of Biochemistry Duke University Medical School, Durham, North Carolina 1965-1971 Professor Department of Biochemistry Duke University Medical School, Durham, North Carolina 1971-Present Professor and Chairman Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Houston, Texas 1984-Present Lodwick T. Bolin Professor Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Houston, Texas 1986-1995 Professor of Biotechnology Center for Biotechnology Baylor College of Medicine, Houston, Texas 1990-Present Distinguished Service Professor L. T. Bolin Professor Chairman Emeritus Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine, Houston, Texas SABBATICAL STUDIES: 1968-1969 D:\582729855.doc Visiting Professor Pasteur Institut, Paris, France Wakil, Salih J. ACADEMIC AND PROFESSIONAL HONORS: 1967 1968-1969 1973 1985 1988-1989 1988 1990 1990 1990 1990 1992 1993 1997 2001 2001 2002 2003 2005 2005 2005 Paul Lewis Award, American Chemical Society John Simon Guggenheim Fellowship Distinguished Duke Alumnus Award Chilton Award, University of Texas Southwestern Medical Center, Dallas President, Association of Medical School Departments of Biochemistry The Kuwait Prize, Kuwait Foundation for the Advancement of Sciences Election to the National Academy of Sciences Resolution of Appreciation, Executive Faculty, Baylor College of Medicine Distinguished Service Award, Arab American Medical Association Distinguished Service Professor, Baylor College of Medicine Election to Fellow, the American Academy of Microbiology Supelco/American Oil Chemists’ Society Research Award 1996-1997 Innovator of Biochemistry, Medical College of Virginia, Virginia Commonwealth University The Annual Michael E. DeBakey, M.D., Excellence in Research Award, Baylor College of Medicine Yamanouchi USA Foundation Award Commissioned as Admiral to the Texas Navy, State of Texas Robert & Esther Stadtler Lecturer, The University of Texas M.D. Anderson Cancer Center at Houston Bristol-Myers Squibb Metabolic Research Award Certificate of Congratulation, Texas House of Representatives Senate Resolution No. 75, Senate of the State of Texas SOCIETIES: Member, American Chemical Society Member, American Society for Biochemistry and Molecular Biology Member, The American Society for Cell Biology Member, Phi Lambda Epsilon Member, The Protein Society Member, Sigma Xi Member, American Society for Microbiology Member, American Society for Neurochemistry Member, Association of Medical School Departments of Biochemistry Fellow, American Association for the Advancement of Science Fellow, American Academy of Microbiology Member, National Academy of Sciences Secretary, Section 21 of the National Academy of Sciences, 1993-1995 Liaison to the National Research Council, Section 21 of the National Academy of Sciences, 1999-2001 Committee on Human Rights of the National Academy of Sciences, 2000-2006 Associate Fellow, Third World Academy of Sciences D:\582729855.doc 3 Wakil, Salih J. REVIEW PANELS: 1971-1974, Member, Metabolic Biology Panel National Science Foundation 1971, Physiological Chemistry Study Section National Institutes of Health Ad hoc Member of Several Study Sections National Research Council EDITORIAL BOARDS: D:\582729855.doc Archives of Biochemistry and Biophysics (1976-1979; 1989-2000) Biochemistry International (1984-1992) BioFactors (1986-1990) Biochemistry (1986-1992) Journal of Protein Chemistry (1991-1997) Biochemistry and Molecular Biology International (1993-1999) 4 Wakil, Salih J. 5 HIGHLIGHTS OF DR. SALIH J. WAKIL’S SCIENTIFIC CONTRIBUTIONS Salih Jawad Wakil is the Distinguished Service Professor, L. T. Bolin Professor, and Chairman Emeritus of the Verna and Marrs McLean Department of Biochemistry at Baylor College of Medicine in Houston, Texas. Dr. Wakil is a renowned biochemist of national and international stature whose contributions in the field of fatty acid metabolism, particularly in the area of biosynthesis, have been revolutionary. Through both his own discoveries and those of his laboratory, the discipline of biochemistry has experienced major breakthroughs in areas that had previously been dormant. Dating back to the 1950s, Dr. Wakil’s personal research has changed the direction of the field of biochemistry. His early studies of the mechanism of fatty acid synthesis established the basis for our current understanding of this vital process in biological systems. Dr. Wakil’s observations of the initial steps of fatty acid synthesis refuted the previously held concept that fatty acid synthesis was simply the reversal of fatty acid oxidation. His seminal research, which demonstrated that catabolic and anabolic pathways are different despite having some common reactions, has been accepted and applied to all major pathways involving the metabolism of carbohydrates, lipids, proteins, and nucleic acids. Many of Dr. Wakil’s contributions have been landmarks in the field. He demonstrated carbon dioxide’s stimulatory effect on fatty acid synthesis and that long-chain fatty acids are synthesized by a system independent of β-oxidation. These observations led to the discovery of acetyl-CoA carboxylase and fatty acid synthase, the two key enzymes of fatty acid synthesis. His contributions in this area include not only the discovery of the requirement of CO2 for fatty acid synthesis but also the hitherto unknown function of biotin (vitamin H) as the prosthetic group of acetyl-CoA carboxylase and the identification of malonyl-CoA as the source of the C2 units in the de novo synthesis of long-chain fatty acids in animal tissues. Based on these efforts, Dr. Wakil D:\582729855.doc Wakil, Salih J. 6 extended his studies of fatty acid biosynthesis to the Eschericia coli and identified the individual enzymes that constitute the pathway for fatty acid synthesis in bacteria which offering additional weights into the construction of fatty acid chains in animals. Using the bacterial system, he helped elucidate the role of a protein as the coenzyme for fatty acid synthesis named the acyl carrier protein (ACP) and its prosthetic group — 4’-phosphopantetheinyl moiety, where the acyl intermediates are attached in the reactions of fatty acid synthesis. These achievements earned him the American Chemical Society’s Paul Lewis Award in Enzyme Chemistry in 1967. Dr. Wakil’s continued pioneering work in the field of fatty acid biochemistry includes his study of the structure-function relationship of both yeast and animal fatty acid synthases. By employing techniques of protein chemistry and enzymology to the yeast and animal fatty acid synthases, he and his colleagues elucidated the architecture of these complex enzymes and the organization of the activities along the subunit polypeptides. In recent years, his focus on lipid biosynthesis in eukaryotes has led to his and his colleagues’ discovery that the various enzymatic activities responsible for fatty acid synthesis in eukaryotic systems are organized in large polypeptide chains with multiple catalytic sites. This breakthrough led to the discovery of multifunctional enzymes and a new concept in enzymology that multiple catalytic sites may be organized in a single polypeptide chain. Hence, the discovery of the multifunctional enzyme called fatty acid synthases dispelled a long-held concept that linked individual genes to the production of single enzymes — the one-gene, one enzyme hypothesis. The yeast fatty acid synthase (Mr = 2.5 x 106) consists of two multifunctional proteins, α and β, which are organized in a α6β6 complex. The seven catalytic activities plus acyl-carrier protein required for fatty acid synthesis are divided between the α and β subunits such that the α6 β6 complex has six complements of each activity. The finding that there are 6 mol of fatty acids synthesized per mol enzyme led Wakil and his group to propose that the yeast fatty acid synthase D:\582729855.doc Wakil, Salih J. 7 has six equivalent centers of fatty acid synthesis each of which contains the seven catalytic domains; hence, the enzyme is a proficient factory for fatty acid synthesis. Moreover, the structure of the yeast fatty acid synthase was examined by negative-stain and electron cryomicroscopy. A three-dimensional structure was proposed for the yeast enzyme as a prolate ellipsoid and that the six fatty acid synthesizing centers are composed of two complementary halves - α subunit and a β subunit, an arrangement having all the activities of the multifunctional enzyme required for fatty acid synthesis. In animals, including humans, the fatty acid synthase (FAS) is a homodimer, and each subunit contains six catalytic centers, each carrying out a specific reaction and together with the acyl carrier protein (ACP), they generate long-chain fatty acids. Throughout the elongation process, the acyl group is linked as a thioester to the 4’-phosphopantetheinyl-SH of the ACP component of FAS. In the native FAS, the two subunits are arranged in an anti-parallel (X) configuration generating two independent active sites on the enzyme each composed of a combination of complementary catalytic centers from each monomer. This arrangement was confirmed by enzymatic, chemical, and genetic studies, as well as by structural electron cryomicroscopy and computational analyses. Most recently, Dr. Wakil has focused his work on the enzyme called acetyl-CoA carboxylase or ACC and its two isoforms, ACC1 and ACC2. He has genetically engineered what have come to be called “magic mice,” which do not produce ACC2, and as a result, can eat 20-30 percent more food and still weigh 10 percent less than mice that produce the enzyme. Not only do they not gain weight, but they also do not develop type 2 diabetes. The hope is that a drug may be developed that can inhibit ACC2, potentially protecting people who might become type 2 diabetics by preventing the accumulation of fat in the muscle, heart, and liver. These findings come at an opportune time when the developed world is facing an obesity epidemic that threatens D:\582729855.doc Wakil, Salih J. 8 to markedly increase rates of heart disease and type 2 diabetes. Wakil’s discoveries point to new and important directions leading to potential new targets for drugs that could help control the development of type 2 diabetes as well as obesity. His contribution to the mechanisms of fatty acid synthesis and oxidation at both the molecular and genetic levels has significantly advanced science. In commenting on Dr. Wakil’s report on the ACC2 knockout mice, the National Institute of General Medical Sciences (NIGMS) wrote on July 2, 2001, “Congratulations! NIGMS is featuring the work you published in Science magazine in our Congressional Budget Justification as one of our top 10-12 advances this year.” Dr. Salih J. Wakil has had a distinguished career by any standard. It spans five decades of high quality, rigorously quantitative, creative research science. It spans the gamut of organisms from E coli to yeast to mice to humans and the range of techniques from protein purification to enzymology to recombinant DNA to gene knockouts. What has remained constant — virtually the only thing — is his utter fascination with fat metabolism and his deep commitment to its complete understanding. He has contributed a series of landmark discoveries, any one of which would highlight a normal career. Dr. Wakil’s experimental insights into the mechanisms and physiology of fat metabolism have illuminated normal metabolism and provided potential new targets for the therapeutic intervention in the aberrant fat metabolism associated with certain human diseases such as obesity, diabetes (especially type 2), and heart attack. Dr. Wakil’s positions include an assistant professorship (’59-’60), an associate professorship (’60-’65), and a professorship (’65-’71). For the period 1971-2005, Dr. Wakil was the Distinguished Service Professor, L. T. Bolin Professor and Chairman of the Verna and Marrs McLean Department of Biochemistry and Molecular Biology. From 2005 - present, he is the D:\582729855.doc Wakil, Salih J. 9 Distinguished Service Professor, L.T. Bolin Professor, and Chairman Emeritus of the Verna and Marrs McLean Department of Biochemistry and Molecular Biology. Dr. Wakil has received national and internal recognition for his scientific contributions. He received the Paul Lewis Award from the American Chemical Society (1967), the Distinguished Duke Alumnus Award (1973), the Chilton Award, University of Texas Southwestern Medical Center, Dallas (1985), the Kuwait Prize from the Kuwait Foundation for the Advancement of Sciences (1988), election to the American Academy of Sciences (1990), the Supelco/American Oil Chemists’ Society Research Award (1993), the Innovator of Biochemistry Award from the Virginia Commonwealth University (1997), the Annual Michael E. DeBakey, M.D., Excellence in Research Award from Baylor College of Medicine (2001), the Yamanouchi USA Foundation Award (2001), and the Bristol-Meyers Squibb Metabolic Research Award (2005). As a Texan, Dr. Wakil has had the honor of being commissioned as an Admiral of the Texas Navy by Governor Rick Perry (2002) and is proud to have been recognized by the Texas House of Representatives that presented him with a congratulatory certificate and by the Senate of the State of Texas that honored him with Senate Resolution No. 75 in 2005 for receiving the Bristol-Meyers Award. D:\582729855.doc Wakil, Salih J. 10 PAPERS OF SPECIAL SIGNIFICANCE (Boldfaced Numbers in Parentheses Refer to Citations in the Publications List) FATTY ACID OXIDATION: 1. Reconstitution of the fatty acid oxidizing system (4 1953) 2. Enzymes of -oxidation of fatty acids (6 1953; 7, 9 1954; 12 1956) FATTY ACID SYNTHESIS IN ANIMAL TISSUES: 1. Discovery of the de novo pathway of palmitate synthesis (15 1957) 2. Bicarbonate requirement and isolation of malonyl-CoA as an intermediate in fatty acid synthesis (18, 19 1958) 3. Discovery of the biotin enzyme, acetyl-CoA carboxylase (17 1958; 26 1960; 36 1962) 4. Discovery of fatty acid synthase (32 1961; 34 1962) FATTY ACID SYNTHESIS IN BACTERIA (Escherichia coli): 1. Acyl carrier protein (ACP) and its pantetheine prosthetic group (53 1964; 55 1965) 2. Mechanism of fatty acid synthesis (52 1964) 3. Isolation and identification of soluble enzymes (56, 59, 60 1966; 64, 65, 66 1968) DESATURATION OF LONG-CHAIN FATTY ACIDS: 1. Requirement for lipids (72 1969) 2. Requirement for NADH-cytochrome b5 reductase (80 1970) MECHANISM OF ACTION OF EUKARYOTIC FATTY ACID SYNTHASE: 1. 2. 3. 4. Multifunctional nature (101 1975; 104 1976; 112 1978) Characterization of synthase mRNA (118 1980; 120 1981) Structural organization of synthase subunits (119 1980; 121, 123 1981; 126 1982) Relationship of structure to function and mechanism (136, 137, 138, 139 1983; 141 1984; 145, 146 1985; 152 1987; 159 1988; 165 1990; 166 1991; 169 1993) 5. Structure of genes coding for synthase proteins (130 1983; 151 1987; 155, 158 1988; 160 1989) 6. Regulation and expression of synthase (172 1994; 175 1996; 180 1998; 182 2000) 7. Cloning and expression of human fatty acid synthase (176 1996; 179 1997; 183, 2001) ACETYL-CoA CARBOXYLASE: 1. Physiologic significance of covalent and allosteric modification (147 1986; 153, 154 1988) 2. Hormonal regulation of acetyl-CoA carboxylase (164 1990) 3. Structure of cDNA coding for acetyl-CoA carboxylases, identification of two isozymes (167 1992; 173 1995; 177 1997) 4. Subcellular localization of acetyl-CoA carboxylases ACC1 and ACC2 (181 2000) 5. Acetyl-CoA carboxylase knockout mice and the proposal that pharmacological D:\582729855.doc Wakil, Salih J. 11 manipulation of ACC2 may lead to loss of body fat in the context of normal caloric intake (184 2001) 6. Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high carbohydrate diets. Fatty acid oxidation rates in the soleus muscle and in hepatocytes of Acc2-/- mice were significantly higher than those of WT cohorts and were not affected by the addition of insulin. mRNA levels of uncoupling proteins (UCPs) were significantly higher in adipose, heart (UCP2), and muscle (UCP3) tissues of mutant mice compared with those of the WT. The increase in the UCP levels along with increased fatty acid oxidation may play an essential role in the regulation of energy expenditure. These results suggest that ACC2 plays an essential role in controlling fatty acid oxidation and is a potential target in therapy against obesity and related diseases (190 2003) THESIS SUPERVISION: 1962 1964 1965 1966 1968 1969 1969 1970 1972 B. M. Waite S. C. Boone Elizabeth L. Pugh Richard E. Toomey Peter D. Jones Eugene M. Barnes, Jr. Charles A. Plate Mojtaba Esfahani M. L. S. Polacco 1976 1979 Carlos GeorgeNascimento Zendra E. Zehner 1980 James David Crisp 1982 Howard Wong 1984 Michael A. Kuziora 1987 Nirpinder Singh 1990 Mehran Pazirandeh 1993 Ming-Hong Tai 1995 Matthew H. Hsu D:\582729855.doc Studies on Acetyl-CoA Carboxylase The Site and Synthesis of Lignocertic and Nervonic Acids The Mechanism of Fatty Acid Synthesis in Escherichia coli Studies on Fatty Acid Biosynthesis in Escherichia coli Studies on the Lipid Requirement of Microsomal Enzymes Studies of Two Palmityl Thioesterases from Escherichia coli Studies on the Fatty Acid Synthetase from Pigeon Liver Regulation of Fatty Acid Metabolism in Escherichia coli Fatty Acid Metabolism in a Biotin Auxotroph of Escherichia coli K12 The Assembly and Mode of Incorporation of Lipids and Proteins into Membranes of Escherichia coli The Regulation of Fatty Acid Synthetase in the Perinatal Chick and the Partial Purification of Synthetase Messenger RNA The Isolation and Partial Characterization of the Palmityl Thioesterase from Chicken Liver Fatty Acid Synthetase The Arrangement of Catalytic Centers and the Isolation and Characterization of the -Ketoacyl Reductase Domain of the Multifunctional Fatty Acid Synthetase Molecular Cloning and Characterization of the Yeast Fatty Acid Synthase Genes Mechanism and Structure to Function Relationship of Eukaryotic Fatty Acid Synthase Expression, Characterization, and Site-Directed Mutagenesis Studies on the Thioesterase Domain of the Chicken Fatty Acid Synthase Expression, Purification, and Mutagenesis Studies of Rat Medium-Chain SAcyl Fatty Acid Synthase Thioesterase II (TE II) Cloning and Characterization of the Human Fatty Acid Synthase Gene: Two Promoters and Their Interactions Wakil, Salih J. 12 POST DOCTORAL FELLOWS AND RESEARCH ASSOCIATES Eighty-six (86) Doctoral Fellows and Research Associates, many of whom are now Professors, Deans, and Chairs in many institutions all over the world. PRINCIPAL INVESTIGATOR OF GRANTS Forty-three (43) years of continuous grant support from the National Institute of Health, grant support from the National Science Foundation, and many private foundations. BOOK Lipid Metabolism, Salih J. Wakil, Editor, 1970, Academic Press, New York, London D:\582729855.doc Wakil, Salih J. 13 REVIEW ARTICLES 1. Wakil, S. J. (1960) The mechanism of fatty acid synthesis. J. Clin. Nutr. 8, 630-642. 2. Green, D. E., and Wakil, S. J. (1960) Enzymatic mechanisms of fatty acid oxidation and synthesis; in Lipid Metabolism (Bloch, K., ed), pp. 1-69, John Wiley and Sons, New York. 3. Wakil, S. J. (1961) The mechanism of fatty acid synthesis. J. Lipid Res. 2, 1-24. 4. Wakil, S. J. (1962) Lipid metabolism. Ann. Rev. Biochem. 31, 369-406. 5. Wakil, S. J., and Bressler, R. (1962) Fatty acid metabolism and ketone body formation. Metabolism 11, 742. 6. Wakil, S. J. (1962) Enzymatic synthesis of fatty acids. Comp. Biochem. Physiol. 4, 123158. 7. Wakil, S. J. (1963) Enzymatic synthesis of fatty acid in the biosynthesis of lipids; in Unknown Title (Popjak, G., ed), pp. 3-34, Polish Scientific Publishers, Warsaw. 8. Wakil, S. J. (1964) The synthesis of fatty acid in animal tissues; in Metabolism and Physiological Significance of Lipids: Proceedings of the NATO Conference on the Biochemical and Physiological Significance of Lipids (Dawson, R. M. C., and Rhodes, D. M., eds), pp. 155-185, John Wiley and Sons, New York. 9. Wakil, S. J. (1965) The synthesis of fatty acids in animal tissues; in Metabolism of Lipids as Related to Atherosclerosis (Kummerow, F., ed), pp. 155-185, Charles C. Thomas, New York. 10. Wakil, S. J., Mizugaki, M., Shapiro, M., and Weeks, G. (1968) The fatty acid synthesizing system of Escherichia coli; in Membrane Models and the Formation of Biological Membranes: Proceedings of the 1967 Meeting of the International Conference on Biological Membranes (Bolis, L., and Pethica, B. A., eds), pp. 122-137, North-Holland Publishing Company, Amsterdam. 11. Wakil, S. J., ed (1970) Treatise on the Metabolism and Function of Lipids, pp. 1-613, Academic Press, New York. 12. Wakil, S. J. (1970) Fatty acid metabolism; in Lipid Metabolism (Wakil, S. J., ed), pp. 1-48, Academic Press, New York. 13. Wakil, S. J., and Esfahani, M. (1971) The response of Escherichia coli to fatty acid supplements and the regulation of membrane lipid synthesis; in Biochemical Responses to Environmental Stress (Bernstein, I. A., ed), pp. 15-31, Plenum Press, New York. 14. Wakil, S. J., and Barnes, E. M., Jr. (1971) Fatty acid metabolism; in Comprehensive Biochemistry (Florkin, M., and Stotz, E. M., eds), Vol. 18S, pp. 57-104, Elsevier Publishing Company, New York. 15. Wakil, S. J., and Esfahani, M. (1972) The role of lipids in the structure and function of D:\582729855.doc Wakil, Salih J. 14 Escherichia coli membrane; in Current Trends in the Biochemistry of Lipids (Ganguly, J., and Smellie, R. M. S., eds), pp. 395-405, Academic Press, New York. 16. George-Nascimento, C., Zehner, Z. E., and Wakil, S. J. (1974) Assembly of lipids and proteins in Escherichia coli membranes. J. Supramolecular Struct. 2, 626-669. 17. Stoops, J. K., Arslanian, M. J., Chalmers, J. H., Jr., Joshi, V. C., and Wakil, S. J. (1977) Fatty acid synthetase complexes; in Bioorganic Chemistry: A Treatise to Supplement Bioorganic Chemistry, An International Journal (van Tamelen, E. E., ed), Vol. 1, pp. 339370, Academic Press, New York. 18. Wakil, S. J., Stoops, J. K., and Mattick, J. S. (1981) The fatty acid synthetase: Structurefunction relationship and mechanism of palmitate synthesis. Cardiovasc. Center Res. Bull. 20, 1-23. 19. Wakil, S. J., Stoops, J. K., and Joshi, V. C. (1983) Fatty acid synthesis and its regulation. Ann. Rev. Biochem. 52, 537-579. 20. Wakil, S. J., and Stoops, J. K. (1983) Fatty acid formation; in The Enzymes: Lipid Metabolism (Boyer, P. D., ed), 3rd Ed., Vol. 16, pp. 3-61, Academic Press, New York. 21. Wakil, S. J., and Kuziora, M. A. (1983) Yeast fatty acid synthetase: Structure-function and molecular cloning of subunits; in Manipulation and Expression of Genes in Eukaryotes (Nagley, P., Linnane, A. W., Peacock, W. J., and Pateman, J. A., eds), pp. 131-140, Academic Press, Sydney. 22. Wakil, S. J., and Stoops, J. K. (1985) Fatty acid synthetases of eukaryotic cells; in The Enzymes of Biological Membranes (Martonosi, A. N., ed), 2nd Ed., Vol. 2, pp. 59-109, Plenum Publishing Corp., New York. 23. Thampy, K. G., and Wakil, S. J. (1986) The role of protein phosphorylation in the regulation of acetyl-CoA carboxylase. Adv. Protein Phosphatases 3, 257-269. 24. Wakil, S. J. (1986) The relationship between structure and function for the regulation of the enzymes of fatty acid synthesis. Ann. NY Acad. Sci. 478, 203-219. 25. Wakil, S. J. (1986) The structure-function and regulation of the enzymes of fatty acid synthesis; in Proceedings of the IVth International Meeting of the Danubian League Against Thrombosis and Hemorrhagic Diseases (Ulutin, O. N., and Vinazzer, H., eds), pp. 17-33, Gozlem Matbaacilik Koll. Sti., Istanbul, Turkey. 26. Wakil, S. J. (1989) The fatty acid synthase: A proficient multifunctional enzyme. Biochemistry 28, 4523-4530. D:\582729855.doc Wakil, Salih J. 15 PUBLICATIONS 1. Hanahan, D. J., and Wakil, S. J. (1952) The biosynthesis of ergosterol from isotopic acetate. Arch. Biochem. Biophys. 37, 167-171. 2. Hanahan, D. J., and Wakil, S. J. (1953) Studies on absorption and metabolism of ergosterol 14C. Arch. Biochem. Biophys. 44, 150-158. 3. Hanahan, D. J., and Wakil, S. J. (1953) The origin of some of the carbon atoms of the side chain of 14C ergosterol. J. Am. Chem. Soc. 75, 273-275. 4. Beinert, H., Bock, R. M., Goldman, D. S., Green, D. E., Mahler, H. R., Mii, S., Stansley, P. G., and Wakil, S. J. (1953) The reconstitution of the fatty acid oxidizing system in animal tissues. J. Am. Chem. Soc. 75, 4111-4112. 5. Mahler, H. R., Wakil, S. J., and Bock, R. M. (1953) Studies on fatty acid oxidation: I. Enzymatic activation of fatty acids. J. Biol. Chem. 204, 453-468. 6. Wakil, S. J., and Mahler, H. R. (1953) Activation of fatty acids by adenosinetriphosphate. Fed. Proc. 12, 285. 7. Wakil, S. J., and Mahler, H. R. (1954) Studies on the fatty acid oxidizing system of animal tissues: V. Unsaturated fatty acyl coenzyme A hydrase. J. Biol. Chem. 207, 125132. 8. Wakil, S. J. (1954) Cleavage of isocrotonyl coenzyme A. Fed. Proc. 13, 316. 9. Wakil, S. J., Green, D. E., Mii, S., and Mahler, H. R. (1954) Studies on the fatty acid oxidizing system of animal tissues: -hydroxyacyl coenzyme A dehydrogenase. J. Biol. Chem. 207, 631-638. 10. Wakil, S. J. (1955) D(-) -hydroxybutyryl coenzyme A dehydrogenase. Biochim. Biophys. Acta 18, 314-315. 11. Wakil, S. J. (1955) D(-) -hydroxybutyryl coenzyme A dehydrogenase. Fed. Proc. 14, 300. 12. Wakil, S. J. (1956) Studies on the fatty acid oxidizing system of animal tissues: IX. Stereospecificity of unsaturated acyl-CoA hydrase. Biochim. Biophys. Acta 19, 497-504. 13. Wakil, S. J., Porter, J. W., and Tietz, A. (1956) Fatty acid synthesis by a soluble enzyme system. Fed. Proc. 15, 377. 14. Gibson, D. M., Jacob, M., Porter, J. W., Tietz, A., and Wakil, S. J. (1957) Biosynthesis of fatty acids by soluble enzyme fractions. Biochim. Biophys. Acta 23, 219-220. 15. Wakil, S. J., Porter, J. W., and Gibson, D. M. (1957) Studies on the mechanism of fatty acid synthesis: I. Preparation and purification of an enzyme system for reconstruction of D:\582729855.doc Wakil, Salih J. 16 fatty acid synthesis. Biochim. Biophys. Acta 24, 453-461. 16. Porter, W. J., Wakil, S. J., Tietz, A., Jacob, M., and Gibson, D. M. (1957) Studies on the mechanism of fatty acid synthesis: II. Cofactor requirements of the soluble pigeon liver system. Biochim. Biophys. Acta 25, 35-41. 17. Gibson, D. M., Titchener, E. B., and Wakil, S. J. (1958) Requirement for bicarbonate in fatty acid synthesis. J. Am. Chem. Soc. 80, 2908. 18. Wakil, S. J., Titchener, E. B., and Gibson, D. M. (1958) Evidence for the participation of biotin in the enzyme synthesis of fatty acids. Biochim. Biophys. Acta 29, 225-226. 19. Wakil, S. J. (1958) A malonic acid derivative as an intermediate in fatty acid synthesis. J. Am. Chem. Soc. 80, 6465. 20. Gibson, D. M., Titchener, E. B., and Wakil, S. J. (1958) Studies on the mechanism of fatty acid synthesis: V. Bicarbonate requirements for the synthesis of long-chain fatty acids. Biochim. Biophys. Acta 30, 376-383. 21. Wakil, S. J., and Ganguly, J. (1959) On the mechanism of fatty acid synthesis. J. Am. Chem. Soc. 81, 2597. 22. Wakil, S. J., Titchener, E. B., and Gibson, D. M. (1959) Studies on the mechanism of fatty acid synthesis: IV. Spectrophotometric assay and stoichiometry of fatty acid synthesis. Biochim. Biophys. Acta 34, 227-233. 23. Wakil, S. J., and Ganguly, J. (1959) On the mechanism of fatty acid synthesis. Fed. Proc. 18, 346. 24. Wakil, S. J. (1960) Biosynthesis of fatty acids. Fed. Proc. 19, 27. 25. Wakil, S. J., and Hubscher, G. (1960) Quantitative determination of coenzyme A by sorbyl coenzyme A formation. J. Biol. Chem. 235, 1554-1558. 26. Wakil, S. J., and Gibson, D. M. (1960) Studies on the mechanism of fatty acid synthesis: VIII. The participation of protein-bound biotin in the biosynthesis of fatty acids. Biochim. Biophys. Acta 41, 122-129. 27. Wakil, S. J., McLain, L. W., and Warshaw, J. B. (1960) Synthesis of fatty acids by mitochondria. J. Biol. Chem. 235, 31-32. 28. Wakil, S. J. (1960) The mechanism of fatty acid synthesis. J. Clin. Nutr. 8, 630-642. 29. Green, D. E., and Wakil, S. J. (1960) Enzymatic mechanisms of fatty acid oxidation and synthesis; in Lipid Metabolism (Bloch, K., ed), pp. 1-35, John Wiley and Sons, New York. 30. Wakil, S. J. (1961) The mechanism of fatty acid synthesis. J. Lipid Res. 2, 1-24. D:\582729855.doc Wakil, Salih J. 17 31. Bressler, R., and Wakil, S. J. (1961) Studies on the mechanism of fatty acid synthesis: IX. The conversion of malonyl-CoA to long-chain fatty acids. J. Biol. Chem. 263, 1643-1651. 32. Bressler, R., and Wakil, S. J. (1961) Synthesis of long-chain fatty acids. Fed. Proc. 20, 274. 33. Wakil, S. J., and Bressler, R. (1962) Studies on the mechanisms of fatty acid synthesis: X. Reduced triphosphopyridine nucleotide-aceto-acetyl coenzyme A reductase. J. Biol. Chem. 237, 687-693. 34. Bressler, R., and Wakil, S. J. (1962) Studies on the mechanism of fatty acid synthesis: XI. The products of the reaction and role of sulfhydryl groups in the synthesis of fatty acids. J. Biol. Chem. 237, 1441-1448. 35. Wakil, S. J. (1962) Lipid metabolism. Ann. Rev. Biochem. 31, 369-406. 36. Waite, M., and Wakil, S. J. (1962) Studies on the mechanism of fatty acid synthesis: XII. Acetyl-CoA carboxylase. J. Biol. Chem. 237, 2750-2757. 37. Wakil, S. J., and Bressler, R. (1962) Fatty acid metabolism and ketone body formation. Metabolism 11, 742-761. 38. Lee, S. D., Bressler, R., and Wakil, S. J. (1962) The enzymatic synthesis of fatty acids. Fed. Proc. 21, 289. 39. Wakil, S. J., and Waite, M. (1962) On the mechanism of action of enzyme-bound biotin. Biochem. Biophys. Res. Commun. 9, 18-24. 40. Wakil, S. J. (1962) Enzymatic synthesis of fatty acids. Comp. Biochem. Physiol. 4, 123158. 41. Harlan, W. R., and Wakil, S. J. (1962) The pathways of synthesis of fatty acids by mitochondria. Biochem. Biophys. Res. Commun. 8, 131-135. 42. Waite, M., and Wakil, S. J. (1963) Studies on the mechanism of action of acetyl-CoA carboxylase: I. Effect of isocitrate on the transcarboxylation step of acetyl-CoA carboxylase. J. Biol. Chem. 238, 77-80. 43. Waite, M., and Wakil, S. J. (1963) Studies on the mechanism of action of acetyl-CoA carboxylase: II. On the mechanism of action of enzyme-bound biotin. J. Biol. Chem. 238, 81-90. 44. Wakil, S. J. (1963) Enzymatic synthesis of fatty acid in the biosynthesis of lipids; in Unknown Title (Popjak, G., ed), pp. 3-34, Polish Scientific Publishers, Warsaw. 45. Wakil, S. J. (1963) β-Hydroxyacyl-CoA Dehydrogenases; in The Enzymes (Boyer, P. D., Lardy, H., and Myrback, K., eds), pp. 97-103, Academic Press, New York. D:\582729855.doc Wakil, Salih J. 18 46. Wakil, S. J. (1963) Malonyl coenzyme A. Methods Enzymol. 51, 540-544. 47. Holloway, P. W., Peluffo, R., Harlan, W. R, and Wakil, S. J. (1963) Biosynthesis of fatty acid by animal tissue. Fed. Proc. 22, 362. 48. Holloway, P. W., Peluffo, R., and Wakil, S. J. (1963) On the biosynthesis of dienoic fatty acids by animal tissues. Biochem. Biophys. Res. Commun. 12, 300-304. 49. Harlan, W. R., Jr., and Wakil, S. J. (1963) Synthesis of fatty acids in animal tissues: Incorporation of 14acetyl coenzyme A into a variety of long-chain fatty acids by subcellular particles. J. Biol. Chem. 238, 3216-3223. 50. Wakil, S. J. (1964) The synthesis of fatty acids in animal tissues; in Metabolism and Physiological Significance of Lipids: Proceedings of the Nato Conference on the Biochemical and Physiological Significance of Lipids (Dawson, R. M. C., and Rhodes, D. M., eds), pp. 155-185, John Wiley and Sons, New York. 51. Holloway, P. W., and Wakil, S. J. (1964) Synthesis of fatty acids in animal tissues: II. The occurrence and biosynthesis of cis-vaccenic acids. J. Biol. Chem. 239, 2489-2495. 52. Wakil, S. J., Pugh, E. L., and Sauer, F. (1964) The mechanism of fatty acid synthesis. Proc. Natl. Acad. Sci. USA 52, 106-114. 53. Sauer, F., Pugh, E. L., Wakil, S. J., Delaney, R., and Hill, R. L. (1964) 2-Metcaptoethylamine and -alanine as components of acyl carrier protein. Proc. Natl. Acad. Sci. USA 52, 1360-1366. 54. Wakil, S. J. (1965) The synthesis of fatty acids in animal tissues; in Metabolism of Lipids as Related to Atherosclerosis (Kummerow, F., ed), pp. 155-185, Charles C. Thomas, New York. 55. Pugh, E. L., and Wakil, S. J. (1965) Studies on the mechanism of fatty acid synthesis: XIV. The prosthetic group of acyl carrier protein and the mode of its attachment to the protein. J. Biol. Chem. 240, 4727-4733. 56. Toomey, R. E., and Wakil, S. J. (1966) Studies on the mechanism of fatty acid synthesis: XVI. Preparation and general properties of acyl-malonyl-ACP condensing enzyme from Escherichia coli. J. Biol. Chem. 241, 1159-1165. 57. Wakil, S. J., Goldman, J. K., Williamson, I. P., and Toomey, R. E. (1966) Stimulation of fatty acid biosynthesis by phosphorylated sugars. Proc. Natl. Acad. Sci. USA 55, 880-887. 58. Waite, B. M., and Wakil, S. J. (1966) Studies on the mechanism of action of acetyl coenzyme A carboxylase: III. 1-N-carboxamide of enzyme-bound biotin as the carboxylation intermediate. J. Biol. Chem. 241, 1909-1914. 59. Toomey, R. E., and Wakil, S. J. (1966) Studies on the mechanism of fatty acid synthesis: XV. Preparation and general properties of -ketoacyl ACP reductase from Escherichia coli. Biochim. Biophys. Acta 116, 189-197. D:\582729855.doc Wakil, Salih J. 19 60. Williamson, I. P., and Wakil, S. J. (1966) Studies on the mechanism of fatty acid synthesis: XVII. Preparation and general properties of acetyl-CoA and malonyl-CoA acyl carrier protein transacylases. J. Biol. Chem. 241, 2326-2332. 61. Pugh, E. L., Sauer, F., Waite, B. M., Toomey, R. E., and Wakil, S. J. (1966) Studies on the mechanism of fatty acid synthesis: The role of -hydroxyl acids in the synthesis of palmitate and cis-vaccenate by the Escherichia coli enzyme system. J. Biol. Chem. 241, 2635-2643. 62. Veeravagu, P., Mizugaki, M., and Wakil, S. J. (1967) A micromethod for identification of hydroxy acids. Anal. Biochem. 23, 403-412. 63. Jones, P. D., and Wakil, S. J. (1967) A requirement for phospholipids by the microsomal reduced diphosphopyridine nucleotide-cytochrome C reductase. J. Biol. Chem. 242, 52675273. 64. Weeks, G., and Wakil, S. J. (1968) Studies on the mechanism of fatty acid synthesis: XVIII. Preparation and general properties of the enoyl acyl carrier protein reductases from Escherichia coli. J. Biol. Chem. 243, 1180-1189. 65. Barnes, E. M. Jr., and Wakil, S. J. (1968) Studies on the mechanism of fatty acid synthesis: XIX. Preparation and general properties of palmityl thioesterase. J. Biol. Chem. 243, 2955-2962. 66. Mizugaki, M., Weeks, G., Toomey, R. E., and Wakil, S. J. (1968) Studies on the mechanism of fatty acid synthesis: XX. Preparation and general properties of hydroxybutyryl acyl carrier protein dehydrase. J. Biol. Chem. 243, 3661-3670. 67. Plate, C. A., Joshi, V. C., Sedgwick, B., and Wakil, S. J. (1968) Studies on the mechanism of fatty acid synthesis: XXI. The role of fructose 1,6-diphosphate in the stimulation of the fatty acid synthetase from pigeon liver. J. Biol. Chem. 243, 5439-5445. 68. Wakil, S. J., Mizugaki, M., Shapiro, M., and Weeks, G. (1968) The fatty acid synthesizing system of Escherichia coli; in Membrane Models and the Formation of Biological Membranes: Proceedings of the 1967 Meeting of the International Conference on Biological Membranes (Bolis, L., and Pethica, B. A., eds), pp. 122-137, North-Holland Publishing Company, Amsterdam. 69. Mizugaki, M., Swindell, A. C., and Wakil, S. J. (1968) Intermediate- and long-chain -hydroxyacyl-ACP dehydrases from Escherichia coli fatty acid synthetase. Biochem. Biophys. Res. Commun. 33, 520-527. 70. Vanaman, T. G., Wakil, S. J., and Hill, R. L. (1968) The preparation of tryptic, peptic, thermolysin and cyanogen bromide peptides from the acyl carrier protein of Escherichia coli. J. Biol. Chem. 243, 6409-6419. 71. Vanaman, T. G., Wakil, S. J., and Hill, R. L. (1968) The complete amino acid sequence of the acyl carrier protein from Escherichia coli. J. Biol. Chem. 243, 6420-6431. 72. Jones, P. D., Holloway, P. W., Peluffo, R. O., and Wakil, S. J. (1969) A requirement for D:\582729855.doc Wakil, Salih J. 20 lipids by the microsomal stearyl coenzyme A desaturase. J. Biol. Chem. 244, 744-754. 73. Weeks, G., Shapiro, M., Burnes, R. O., and Wakil, S. J. (1969) The control of fatty acid oxidation in Escherichia coli. J. Bacteriol. 97, 827-836. 74. Hirota, Y., Wakil, S. J., Shapiro, B., Ryter, A., Hurwitz, J., and Jacob F. (1969) Sur un mutant thermosensible d’Escherichia coli presentant des anomalies de la membrane. C. R. Acad. Sci. Paris 269, 1346-1348. 75. Esfahani, M., Barnes, E. M. Jr., and Wakil, S. J. (1969) Control of fatty acid composition in phospholipids of Escherichia coli: Response to fatty acid supplements in a fatty acid auxotroph. Proc. Natl. Acad. Sci. USA 64, 1057-1064. 76. Schulz, H., Weeks, G., Toomey, R. E., Shapiro, M., and Wakil, S. J. (1969) Studies on the mechanism of fatty acid synthesis: XXIII. Salt activation of the fatty acid synthesizing enzymes of Escherichia coli. J. Biol. Chem. 244, 6577-6583. 77. Boone, S. C., and Wakil, S. J. (1970) The in vitro synthesis of lignoceric and nermonic acids in mammalian liver and brain. Biochemistry 9, 1470-1479. 78. Weeks, G., and Wakil, S. J. (1970) Studies on the control of fatty acid metabolism: II. The inhibition of fatty acid synthesis in Lactobacillus plantarum by exogenous fatty acid. J. Biol. Chem. 245, 1913-1921. 79. Wakil, S. J., ed. (1970) Treatise on the Metabolism and Function of Lipids, pp. 1-613, Academic Press, New York. 80. Holloway, P. W., and Wakil, S. J. (1970) Requirements for DPNH-cytochrome b5 reductase in stearyl-CoA desaturation. J. Biol. Chem. 245, 1862-1865. 81. Barnes, E. M. Jr., Swindell, A. C., and Wakil, S. J. (1970) Purification and properties of a palmityl thioesterase II from Escherichia coli. J. Biol. Chem. 245, 3122-3128. 82. Joshi, V. C., Plate, C. A., and Wakil, S. J. (1970) Studies on the mechanism of fatty acid synthesis: XXIII. The acyl binding sites of the pigeon liver fatty acid synthetase. J. Biol. Chem. 245, 2857-2867. 83. Plate, C. A., Joshi, V. C., and Wakil, S. J. (1970) Studies on the mechanism of fatty acid synthesis: XXIV. The acetyl- and malonyl-transacylase activities of the pigeon liver fatty acid synthetase. J. Biol. Chem. 245, 2868-2875. 84. Schulz, H., and Wakil, S. J. (1970) The reactions of hydroxylamine with acetoacetyl thioesterase or ethyl acetoacetate. Anal. Biochem. 37, 457-461. 85. Wakil, S. J. (1970) Fatty acid metabolism; in Lipid Metabolism (Wakil, S. J., ed), pp. 148, Academic Press, New York. 86. Esfahani, M., Ioneda, T., and Wakil, S. J. (1971) Studies on the control of fatty acid metabolism: III. Incorporation of fatty acids into phospholipids and regulation of fatty acid synthetase of Escherichia coli. J. Biol. Chem. 246, 50-56. D:\582729855.doc Wakil, Salih J. 21 87. Schulz, H., and Wakil, S. J. (1971) Studies on the mechanism of fatty acid synthesis: XXV. On the mechanism of -ketoacyl acyl carrier protein reductase from Escherichia coli. J. Biol. Chem. 246, 1895-1901. 88. Wakil, S. J., and Esfahani, M. (1971) The response of Escherichia coli to fatty acid supplements and the regulation of membrane lipid synthesis; in Biochemical Responses to Environmental Stress (Bernstein, I. A., ed), pp. 15-31, Plenum Press, New York. 89. Joshi, V. C., and Wakil, S. J. (1971) Studies on the mechanism of fatty acid synthesis: XXVI. Purification and properties of malonyl-coenzyme A-acyl carrier protein transacylase of Escherichia coli. Arch. Biochem. Biophys. 143, 493-505. 90. Huxstable, R. J., and Wakil, S. J. (1971) Comparative mitochondrial oxidation of fatty acids. Biochim. Biophys. Acta 239, 168-177. 91. Wakil, S. J., and Barnes, E. M. Jr. (1971) Fatty acid metabolism; in Comprehensive Biochemistry (Florkin, M., and Stotz, E. M., eds), Vol. 185, pp. 57-104, Elsevier Science Publishers, New York. 92. Esfahani, M. E., Limbrick, A. R., Knutton, S., Oka, T., and Wakil, S. J. (1971) The molecular organization of lipids in the membrane of Escherichia coli. Proc. Natl. Acad. Sci. USA 68, 3180-3184. 93. Esfahani, M., Limbrick, A. R., Knutton, S., Oka, T., and Wakil, S. J. (1972) The molecular organization of lipids in the membrane of Escherichia coli. Biochem. J. 128, 20. 94. Wakil, S. J., and Esfahani, M. (1972) The role of lipids in the structure and function of Escherichia coli membrane; in Current Trends in the Biochemistry of Lipids (Ganguly, J., and Smellie, R. M. S., eds), pp. 395-405, Academic Press, New York. 95. Esfahani, M., Crowfoot, P. D., and Wakil, S. J. (1972) Molecular organization of lipids in Escherichia coli membranes: II. Effect of phospholipids in succinic-ubiquinone reductase activity. J. Biol. Chem. 247, 7251-7256. 96. Crowfoot, P. D., Oka, T., Esfahani, M., and Wakil, S. J. (1972) Turnover of phospholipids in an unsaturated fatty acid auxotroph of Escherichia coli. J. Bacteriol. 112, 1396-1407. 97. Crowfoot, P. D., Esfahani, M., and Wakil, S. J. (1972) The relation between protein synthesis and phospholipid synthesis and turnover in Escherichia coli. J. Bacteriol. 112, 1408-1415. 98. Okuyama, H., and Wakil, S. J. (1973) Positional specificities of acyl coenzyme A: Glycerophosphate acyl coenzyme A: Monoacylglycerophosphate acyltransferases in Escherichia coli. J. Biol. Chem. 248, 5197-5205. 99. Arslanian, M. J., and Wakil, S. J. (1974) Fatty acid synthetase from chicken liver. Methods Enzymol. 35B, 59-65. 100. George-Nascimento, C., Zehner, Z. E., and Wakil, S. J. (1974) Assembly of lipids and proteins in Escherichia coli membranes. J. Supramol. Struct. 2, 646-669. D:\582729855.doc Wakil, Salih J. 22 101. Stoops, J. K., Arslanian, M., Oh, Y. H., Aune, K. C., Vanaman, T. C., and Wakil, S. J. (1975) Presence of two polypeptide chains comprising the fatty acid synthetase. Proc. Natl. Acad. Sci. USA 72, 1940-1944. 102. Morrisett, J. D., Pownall, H. J., Plumlee, R. T., Smith, L. C., Zehner, Z. E., Esfahani, M., and Wakil, S. J. (1975) Multiple thermotropic phase transitions of Escherichia coli membranes and membrane lipids. J. Biol. Chem. 250, 6969-6976. 103. Okuyama, H., Yamada, K., Ikezawa, H., and Wakil, S. J. (1976) Factors affecting acyl selectivities of acyl-transferases in Escherichia coli. J. Biol. Chem. 251, 2487-2492. 104. Arslanian, M. J., Stoops, J. K., Oh, Y. H., and Wakil, S. J. (1976) On the 4-phosphopantetheine content of chicken and rat liver fatty acid synthetase. J. Biol. Chem. 251, 3194-3196. 105. George-Nascimento, C., Wakil, S. J., Short, S. A., and Kaback, H. R. (1976) Effect of lipids on the reconstitution of D-lactate oxidase in Escherichia coli membrane vesicles. J. Biol. Chem. 251, 6662-6666. 106. Wilson, A. C., Wakil, S. J., and Joshi, V. C. (1976) Induction of microsomal stearyl coenzyme A desaturase in newly hatched chicks. Arch. Biochem. Biophys. 173, 154-161. 107. Wilson, A. C., Murtadha, M., and Wakil, S. J. (1977) Fatty acid synthesis in aorta: Isolation of fatty acid synthetase from chicken aorta. Atherosclerosis 26, 103-115. 108. Stoops, J. K., Arslanian, M. J., Chalmers, J. H., Jr., Joshi, V. C., and Wakil, S. J. (1977) Fatty acid complexes; in Bioorganic Chemistry: A Treatise to Supplement Bioorganic Chemistry, An International Journal (van Tamelen, E. E., ed), Vol. 1, pp. 339-370, Academic Press, New York. 109. Joshi, V. C., Wilson, A. C., and Wakil, S. J. (1977) Assay for the terminal enzyme of the coenzyme A desaturase using chick embryo liver microsomes. J. Lipid Res. 18, 32-36. 110. Zehner, Z. E., Joshi, V. C., and Wakil, S. J. (1977) Regulation of fatty acid synthetase in perinatal chicks: Identification of polysomes synthesizing fatty acid synthetase. J. Biol. Chem. 252, 7015-7022. 111. Stoops, J. K., Arslanian, M. J., Aune, K. C., and Wakil, S. J. (1978) Further evidence for the multifunctional enzyme characteristic of the fatty acid synthetases of animal tissues: Physicochemical studies of the chicken liver fatty acid synthetase. Arch. Biochem. Biophys. 188, 348-359. 112. Stoops, J. K., Awad, E. S., Arslanian, M. J., Gunsberg, S., Wakil, S. J., and Oliver, R. M. (1978) Studies on the yeast fatty acid synthetase: Subunit composition and structural organization of a large multifunctional enzyme complex. J. Biol. Chem. 253, 4464-4475. 113. Joshi, V. C., and Wakil, S. J. (1978) Hormonal regulation of hepatic fatty acid synthetase in chick embryo. J. Biol. Chem. 253, 2120-2125. 114. Stoops, J. K., and Wakil, S. J. (1978) The isolation of the two subunits of yeast fatty acid synthetase. Biochem. Biophys. Res. Commun. 84, 225-231. D:\582729855.doc Wakil, Salih J. 23 115. Stoops, J. K., Ross, P. R., Arslanian, M. J., Aune, K. C., Wakil, S. J., and Oliver, R. O. (1979) Physicochemical studies of the rat liver and adipose fatty acid synthetases. J. Biol. Chem. 254, 7418-7426. 116. Okuyama, H., Saito, M., Joshi, V. C., Gunsberg, S., and Wakil, S. J. (1979) Regulation by temperature of the chain length of fatty acids in yeast. J. Biol. Chem. 254, 12281-12284. 117. Sreekrishna, K., Gunsberg, S., Wakil, S. J., and Joshi, V. C. (1980) Interaction of the fluorescent analogue stearoyl-(1,N6)-etheno coenzyme A with chicken liver acetyl coenzyme A carboxylase. J. Biol. Chem. 255, 3348-3351. 118. Zehner, Z. E., Mattick, J. S., Stuart, R., and Wakil, S. J. (1980) Goose fatty acid synthetase mRNA. J. Biol. Chem. 255, 9519-9522. 119. Stoops, J. K., and Wakil, S. J. (1980) Yeast fatty acid synthetase: Structure-function relationship and the nature of the -ketoacyl synthetase site. Proc. Natl. Acad. Sci. USA 77, 4544-4548. 120. Mattick, J. S., Zehner, Z. E., Calabro, M. A., and Wakil, S. J. (1981) The isolation and characterization of fatty-acid-synthetase mRNA from rat mammary gland. Eur. J. Biochem. 114, 643-651. 121. Stoops, J. K., and Wakil, S. J. (1981) Animal fatty acid synthetase: A novel arrangement of the -ketoacyl synthetase sites comprising domains of the two subunits. J. Biol. Chem. 256, 5128-5133. 122. Wakil, S. J., Stoops, J. K., and Mattick, J. S. (1981) The fatty acid synthetase: Structurefunction relationship and mechanism of palmitate synthesis. Cardiovasc. Res. Center Bull. 20, 1-23. 123. Stoops, J. K., and Wakil, S. J. (1981) The yeast fatty acid synthetase: Structure-function relationship and the role of the active cysteineSH and pantetheineSH. J. Biol. Chem. 256, 8364-8370. 124. Stoops, J. K., and Wakil, S. J. (1982) The reaction of chicken liver fatty acid synthetase with 5,5-dithiobis(2-nitrobenzoic acid). Biochem. Biophys. Res. Commun. 104, 10181024. 125. Aprahamian, S. A., Arslanian, M. J., and Wakil, S. J. (1982) Comparative studies on the kinetic parameters and product analyses of chicken and rat liver and yeast fatty acid synthetase. Comp. Biochem. Physiol. 71B, 577-582. 126. Stoops, J. K., and Wakil, S. J. (1982) Animal fatty acid synthetase: Identification of the residues comprising the novel arrangement of the -ketoacyl synthetase site and their role in its cold inactivation. J. Biol. Chem. 257, 3230-3235. 127. Calabro, M. A., Prasad, M. R., Wakil, S. J., and Joshi, V. C. (1982) Stearoyl-coenzyme A desaturase activity in the mammary gland and liver of lactating rats. Lipids 17, 397-402. 128. Crisp, J. D., and Wakil, S. J. (1982) Chicken liver fatty acid synthetase: Proteolysis of synthetase by subtilizing and isolation and properties of palmitoyl thioesterase. J. Protein Chem. 1, 241-255. D:\582729855.doc Wakil, Salih J. 24 129. Kasturi, R., and Wakil, S. J. (1983) Increase synthesis and accumulation of phospholipids during differentiation of 3T3-L1 cells into adipocytes. J. Biol. Chem. 258, 3559-3564. 130. Kuziora, M. A., Chalmers, J. H. Jr., Douglas, M. G., Hitzeman, R. A., Mattick, J. S., and Wakil, S. J. (1983) Molecular cloning of fatty acid synthetase genes from Saccharomyces cerevisiae. J. Biol. Chem. 258, 11648-11653. 131. Stoops, J. K., Henry, S. J., and Wakil, S. J. (1983) The arrangement and role of some of the amino acid residues in the -ketoacyl synthetase site of chicken liver fatty acid synthetase. J. Biol. Chem. 258, 12482-12486. 132. Shoukry, S., Stoops, J. K., and Wakil, S. J. (1983) Inactivation of yeast fatty acid synthetase by modifying the -ketoacyl reductase active lysine residue with pyridoxal 5-phosphate. Arch. Biochem. Biophys. 226, 224-230. 133. Wakil, S. J. Stoops, J. K., and Joshi, V. C. (1983) Fatty acid synthesis and its regulation. Ann. Rev. Biochem. 52, 537-579. 134. Wakil, S. J., and Stoops, J. K. (1983) Structure and mechanism of fatty acid synthetase; in The Enzymes: Lipid Enzymology (Boyer, P. D., ed), 3rd Ed., Vol. 16, pp. 3-61, Academic Press, New York. 135. Wakil, S. J., and Kuziora, M. A. (1983) Yeast fatty acid synthetase: Structure-function and molecular cloning of subunits; in Manipulation and Expression of Genes in Eukaryotes (Nagley, P., Linnane, A. W., Peacock, W. J., and Patemen, J. A., eds), pp. 131-140, Academic Press, Sydney. 136. Mattick, J. S., Tsukamoto, Y., Nickless, J., and Wakil, S. J. (1983) The architecture of the animal fatty acid synthetase: I. Proteolytic dissection and peptide mapping. J. Biol. Chem. 258, 15291-15299. 137. Mattick, J. S., Nickless, J., Mizugaki, M., Yang, C.-Y., Uchiyama, S., and Wakil, S. J. (1983) The architecture of the animal fatty acid synthetase: II. Separation of the core and thioesterase functions and determination of the N-C orientation of the subunit. J. Biol. Chem. 258, 15300-15304. 138. Wong, H., Mattick, J. S., and Wakil, S. J. (1983) The architecture of the animal fatty acid synthetase: III. Isolation and characterization of -ketoacyl reductase. J. Biol. Chem. 258, 15305-15311. 139. Tsukamoto, Y., Wong, H., Mattick, J. S., and Wakil, S. J. (1983) The architecture of the animal fatty acid synthetase: IV. Active site determination study. J. Biol. Chem. 258, 15312-15322. 140. Yang, C.-Y., and Wakil, S. J. (1984) Separation of dimethylaminoazobenzenethiohydantoin amino acids by high-performance liquid chromatography at low picomole concentrations. Anal. Biochem. 137, 54-57. D:\582729855.doc Wakil, Salih J. 25 141. Singh, N., Wakil, S. J., and Stoops, J. K. (1984) On the question of half- or full-site reactivity of animal fatty acid synthetase. J. Biol. Chem. 259, 3605-3611. 142. Kasturi, R., Joshi, V. C., and Wakil, S. J. (1984) Colchicine inhibition of insulin induction of stearoyl-CoA desaturase and fatty acid synthetase in cultured avian liver explants. Arch. Biochem. Biophys. 233, 530-539. 143. Wakil, S. J., and Stoops, J. K. (1985) Fatty acid synthetases of eucaryotic cells; in The Enzymes of Biological Membranes (Martonosi, A. N., ed), 2nd Ed., Vol. 2, pp. 59-109, Plenum Publishing Corp., New York. 144. Thampy, K. G., and Wakil, S. J. (1985) Activation of acetyl-CoA carboxylase: Purification and properties of a Mn2+-dependent phosphatase. J. Biol. Chem. 260, 6318-6323. 145. Singh, N., Wakil, S. J., and Stoops, J. K. (1985) The development and application of a novel chromophoric substrate for investigation of the mechanism of yeast fatty acid synthase. Biochem. Biophys. Res. Commun. 131, 786-792. 146. Singh, N., Wakil, S. J., and Stoops, J. K. (1985) Yeast fatty acid synthase: Structure to function relationship. Biochemistry 24, 6598-6602. 147. Thampy, K. G., and Wakil, S. J. (1986) The role of protein phosphorylation in the regulation of acetyl-CoA carboxylase. Adv. Protein Phosphatases 3, 257-269. 148. Chirala, S. S., and Wakil, S. J. (1986) Radiolabeling of the PstI restriction fragments and improvement in the sequencing procedure. Gene 47, 297-300. 149. Wakil, S. J. (1986) The relationship between structure and function for the regulation of the enzymes of fatty acid synthesis. Ann. NY Acad. Sci. 478, 203-219. 150. Wakil, S. J. (1986) The structure-function and regulation of the enzymes of fatty acid synthesis; in Proceedings of the IVth International Meeting of the Danubian League Against Thrombosis and Hemorrhagic Diseases (Ulutin, O. N., and Vinazzer, H., eds), pp. 17-33, Gozlem Matbaacilik Koll. Sti., Istanbul, Turkey. 151. Chirala, S. S., Kuziora, M. A., Spector, D. M., and Wakil, S. J. (1987) Complementation of mutations and nucleotide sequence of FAS1 gene encoding subunit of yeast fatty acid synthase. J. Biol. Chem. 262, 4231-4240. 152. Stoops, J. K., Wakil, S. J., Uberbacher, E. C., and Bunick, G. J. (1987) Small-angle neutron-scattering and electron microscope studies of the chicken liver fatty acid synthase. J. Biol. Chem. 262, 10246-10251. 153. Thampy, K. G., and Wakil, S. J. (1988) Regulation of acetyl-coenzyme A carboxylase: I. Purification and properties of two forms of acetyl-coenzyme A carboxylase from rat liver. J. Biol. Chem. 263, 6447-6453. 154. Thampy, K. G., and Wakil, S. J. (1988) Regulation of acetyl-coenzyme A carboxylase: II. Effect of fasting and refeeding on the activity, phosphate content, and aggregation state of D:\582729855.doc Wakil, Salih J. 26 the enzyme. J. Biol. Chem. 263, 6454-6458. 155. Mohamed, A. H., Chirala, S. S., Mody, N. H., Huang, W.-Y., and Wakil, S. J. (1988) Primary structure of the multifunctional subunit protein of yeast fatty acid synthase derived from FAS2 gene sequence. J. Biol. Chem. 263, 12315-12325. 156. Thampy, K. G., Huang, W.-Y., and Wakil, S. J. (1988) A rapid purification method for rat liver pyruvate carboxylase and amino acid sequence: Analyses of NH2-terminal and biotin peptide. Arch. Biochem. Biophys. 266, 270-276. 157. Yang, C.-Y., Huang, W.-Y., Chirala, S., and Wakil, S. J. (1988) Complete amino acid sequence of thioesterase domain of chicken liver fatty acid synthase. Biochemistry 27, 7773-7777. 158. Kasturi, R., Chirala, S., Pazirandeh, M., and Wakil, S. J. (1988) Characterization of a genomic and cDNA clone coding for the thioesterase domain and 3 noncoding region of the chicken liver fatty acid synthase gene. Biochemistry 27, 7778-7785. 159. Tsukamoto, Y., and Wakil, S. J. (1988) Isolation and mapping of the -hydroxyacyl dehydratase activity of chicken liver fatty acid synthase. J. Biol. Chem. 263, 16225-16229. 160. Chirala, S. S., Kasturi, R., Pazirandeh, M., Stolow, D. T., Huang, W.-Y., and Wakil, S. J. (1989) A novel cDNA extension procedure: Isolation of chicken fatty acid synthase cDNA clones. J. Biol. Chem. 264, 3750-3757. 161. Huang, W.-Y., Stoops, J. K., and Wakil, S. J. (1989) Complete amino acid sequence of chicken liver acyl carrier protein derived from the fatty acid synthase. Arch. Biochem Biophys. 270, 92-98. 162. Wakil, S. J. (1989) The fatty acid synthase: A proficient multifunctional enzyme. Biochemistry 28, 4523-4530. 163. Pazirandeh, M., Chirala, S. S., Huang, W.-Y., and Wakil, S. J. (1989) Characterization of recombinant thioesterase and acyl carrier protein domains of chicken fatty acid synthase expressed in Escherichia coli. J. Biol. Chem. 264, 18195-18201. 164. Mabrouk, G. M., Helmy, I. M., Thampy, K. G., and Wakil, S. J. (1990) Acute hormonal control of acetyl-CoA carboxylase: The roles of insulin, glucagon, and epinephrine. J. Biol. Chem. 265, 6330-6338. 165. Stoops, J. K., Singh, N., and Wakil, S. J. (1990) The yeast fatty acid synthase: Pathway for transfer of the acetyl group from coenzyme A to the CysSH of the condensation site. J. Biol. Chem. 265, 16971-16977. 166. Pazirandeh, M., Chirala, S. S., and Wakil, S. J. (1991) Site-directed mutagenesis studies on the recombinant thioesterase domain of chicken fatty acid synthase expressed in Escherichia coli. J. Biol. Chem. 266, 20946-20952. D:\582729855.doc Wakil, Salih J. 27 167. Al-Feel, W., Chirala, S. S., and Wakil, S. J. (1992) Cloning of the yeast FAS3 gene and primary structure of yeast acetyl-CoA carboxylase. Proc. Natl. Acad. Sci. USA 89, 45344538. 168. Stoops, J. K., Kolodziej, S. J., Schroeter, J. P., Bretaudiere, J.-P., and Wakil, S. J. (1992) Structure-function relationships of the yeast fatty acid synthase: Negative-stain, cryoelectron microscopy, and image analysis studies of the end views of the structure. Proc. Natl. Acad. Sci. USA 89, 6585-6589. 169. Tai, M.H., Chirala, S. S., and Wakil, S. J. (1993) Roles of Ser101, Asp236, and His237 in catalysis of thioesterase II and of the C-terminal region of the enzyme in its interaction with fatty acid synthase. Proc. Natl. Acad. Sci. USA 90, 1852-1856. 170. Mohamed, A. H., Huang, W.-Y., Huang, W., Venkatachalam, K. V., and Wakil, S. J. (1994) Isolation and characterization of a novel acetyl-CoA carboxylase kinase from rat liver. J. Biol. Chem. 269, 6859-6865. 171. Huang, W.-Y., Chirala, S. S., and Wakil, S. J. (1994) Amino-terminal blocking group and sequence of the animal fatty acid synthase. Arch. Biochem. Biophys. 314, 45-49. 172. Jayakumar, A., Chirala, S. S., Chinault, A. C., Baldini, A., Abu-Elheiga, L., and Wakil, S. J. (1994) Isolation and chromosomal mapping of genomic clones encoding the human fatty acid synthase gene. Genomics 23, 420-424. 173. Abu-Elheiga, L., Jayakumar, A., Baldini, A., Chirala, S. S., and Wakil, S. J. (1995) Human acetyl-CoA carboxylase: Characterization, molecular cloning, and evidence for two isoforms. Proc. Natl. Acad. Sci. USA 92, 4011-4015. 174. Jayakumar, A., Tai, M.-H., Huang, W.-Y., Al-Feel, W., Hsu, M., Abu-Elheiga, L., Chirala, S. S., and Wakil, S. J. (1995) Human fatty acid synthase: Properties and molecular cloning. Proc. Natl. Acad. Sci. USA 92, 8695-8699. 175. Hsu, M. H., Chirala, S. S., and Wakil, S. J. (1996) Human fatty acid synthase: Evidence for the presence of two promoters and their functional interaction. J. Biol. Chem. 271, 13584-13592. 176. Jayakumar, A., Huang, W. Y., Raetz, B., Chirala, S. S., and Wakil, S. J. (1996) Cloning and expression of the multifunctional human fatty acid synthase and its subdomains in Escherichia coli. Proc. Natl. Acad. Sci. USA 93, 14509-14514. 177. Abu-Elheiga, L., Almarza-Ortega, D. B., Baldini, A., and Wakil, S. J. (1997) Human acetyl-CoA carboxylase 2: Molecular cloning, characterization, chromosomal mapping, and evidence for two isoforms. J. Biol. Chem. 272, 10669-10677. 178. Chirala, S. S., Huang, W. Y., Jayakumar, A., Sakai, K., and Wakil, S. J. (1997) Animal fatty acid synthase: Functional mapping and cloning and expression of the domain I constituent activities. Proc. Natl. Acad. Sci. USA 94, 5588-5593. 179. Jayakumar, A., Chirala, S. S., and Wakil, S. J. (1997) Human fatty acid synthase: Assembling recombinant halves of the fatty acid synthase protein reconstitutes enzyme D:\582729855.doc Wakil, Salih J. 28 activity. Proc. Natl. Acad. Sci. USA 94, 12326-12330. 180. Xiong, S., Chirala, S. S., Hsu, M. H., and Wakil, S. J. (1998) Identification of thyroid hormone response elements in the human fatty acid synthase promoter. Proc. Natl. Acad. Sci. USA 95, 12260-12265. 181. Abu-Elheiga, L., Brinkley, W. R., Zhong, L., Chirala, S. S., Woldegiorgis G., and Wakil, S. J. (2000) The subcellular localization of acetyl-CoA carboxylase 2. Proc. Natl. Acad. Sci. USA 97, 1444-1449. 182. Xiong, S., Chirala, S. S., and Wakil, S. J. (2000) Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites. Proc. Natl. Acad. Sci. USA 97, 3948-3953. 183. Chirala, S. S., Jayakumar, A., Gu, Z., and Wakil, S. J. (2001) Human fatty acid synthase: Role of interdomain in the formation of catalytically active synthase dimer. Proc. Natl. Acad. Sci. USA 98, 3104-3108. 184. Abu-Elheiga, L., Matzuk, M. M., Abo-Hashema, K. A. H., and Wakil, S. J. (2001) Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science, 291, 2613-2616. 185. Brink, J., Ludtke S. J., Yang, C., Gu, Z., Wakil, S. J. and Chiu, W. (2002) Quaternary structure of human fatty acid synthase by electron cryomicroscopy. Proc. Natl. Acad. Sci. USA., 99, 138-143. 186. Ming, D., Yifei, K., Wakil, S. J., Brink, J., Ma, J. (2002) Domain movements in human fatty acid synthase by quantized elastic deformational model. Proc. Natl. Acad. Sci. USA., 99, 7895-7899 187. Al Feel, Walid, DeMar, James C., and Wakil, Salih J. (2003) A Saccharomyces cerevisiae mutant strain defective in acetyl-CoA carboxylase arrests at the G2/M phase of the cell cycle. Proc. Natl. Acad. Sci. USA., 100, 3095-3100. 188. Chirala, Subrahmanyam S., Chang, Hua, Matzuk, Martin, Abu-Elheiga, Lutfi, Mao, Jianqiang, Mahon, Kathleen, Finegold, Milton, and Wakil, Salih J. (2003) Fatty acid synthesis is essential in embryonic development: Fatty acid synthase null mutants and most of the heterozygotes die in utero. Proc. Natl. Acad. Sci. USA., 100, 6558-6363. 189. Mao, Jianqiang, Chirala, Subrahmanyam S., Wakil, Salih J. (2003) Human acetyl-CoA carboxylase 1 gene: presence of three promoters and heterogeneity at the 5’-untranslated mRNA region. Proc. Natl. Acad. Sci. USA., 100, 7515-7520. 190. Lutfi Abu-Elheiga, Wonkeun Oh, Parichher Kordari, and Salih J. Wakil. (2003) ACC2 mutant mice are protected against obesity and diabetes induced by high fat high carbohydrate diets. Proc. Natl. Acad. Sci. USA. Proc. Natl. Acad. Sci. USA., 100, 1020710212. 191. Jacob Brink, Steven J. Ludtke, Yifei Kong, Salih J. Wakil, Jianpeng Ma, and Wah Chiu (2004) Experimental Verification of Conformational Variation of Human Fatty Acid D:\582729855.doc Wakil, Salih J. 29 Synthase as Predicted by Normal Mode Analysis. Structure, 12, 185-191. 192. Chakravarty, Bornali, Gu, Ziwei, Chirala, Subrahmanyam S., Wakil, Salih J., and Quiocho, Florante A. (2004) Human fatty acid synthase: structure and substrate selectivity of the thioesterase domain. Proc Natl Acad Sci U S A. 101:15567-72. 193. Chirala, Subrahmanyam S., and Wakil, Salih J. (2004) Structure and function of animal fatty acid synthase. Lipids, 39:1045-1053. 194. Oh, WonKeun, Abu-Elheiga, Lutfi, Kordari, Parichher, Gu, Ziwei, Shaikenov, Tattym, Chirala, Subrahmanyam. S., and Wakil, S. J. (2005) Glucose and fat metabolism in adipose tissue of ACC2 knockout mice. Proc. Natl. Acad. Sci. USA, 102:1384-1389. 195. Abu-Elheiga, L, Matzuk, M, Kordari, P, Oh, W-K, Shaikenov, T, Gu, Z-W, and Wakil, S.J. (2005) Mutant mice lacking acetyl-coA carboxylase 1 are embryonically lethal. Proc. Natl. Acad. Sci. USA, 102: 12011-12016. 196. Mao J, DeMayo FJ, Li H, Abu-Elheiga L, Gu Z, Shaikenov TE, Kordari P, Chirala SS, Heird WC, Wakil SJ. (2006) Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis. Proc Natl Acad Sci U S A., 103 (22):8552-8557. D:\582729855.doc