Download 9. Wakil, S. J., Green, DE, Mii, S., and Mahler, HR (1954) Studies on

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 SAcyl 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 cysteineSH and pantetheineSH. 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 CysSH 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