Publications

• Fatty acid synthesis and its regulation.

  Wakil S.J., Stoops J.K., Joshi V.C.

  Annu Rev Biochem 52:537-579(1983) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Fatty acid synthesis and elongation in yeast.

  Tehlivets O., Scheuringer K., Kohlwein S.D.

  Fatty acids are essential compounds in the cell. Since the yeast Saccharomyces cerevisiae does not feed typically on fatty acids, cellular function and growth relies on endogenous synthesis. Since all cellular organelles are involved in-- or dependent on--fatty acid synthesis, multiple levels of c ... >> More

  Fatty acids are essential compounds in the cell. Since the yeast Saccharomyces cerevisiae does not feed typically on fatty acids, cellular function and growth relies on endogenous synthesis. Since all cellular organelles are involved in-- or dependent on--fatty acid synthesis, multiple levels of control may exist to ensure proper fatty acid composition and homeostasis. In this review, we summarize what is currently known about enzymes involved in cellular fatty acid synthesis and elongation, and discuss potential links between fatty acid metabolism, physiology and cellular regulation. << Less

  Biochim Biophys Acta 1771:255-270(2007) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together.

  Lomakin I.B., Xiong Y., Steitz T.A.

  In yeast, the whole metabolic pathway for making 16- and 18-carbon fatty acids is carried out by fatty acid synthase, a 2.6 megadalton molecular-weight macromolecular assembly containing six copies of all eight catalytic centers. We have determined its crystal structure, which illuminates how this ... >> More

  In yeast, the whole metabolic pathway for making 16- and 18-carbon fatty acids is carried out by fatty acid synthase, a 2.6 megadalton molecular-weight macromolecular assembly containing six copies of all eight catalytic centers. We have determined its crystal structure, which illuminates how this enzyme is initially activated and then carries out multiple steps of synthesis in each of six sterically isolated reaction chambers. Six of the catalytic sites are in the wall of the assembly facing an acyl carrier protein (ACP) bound to the ketoacyl synthase domain. Two-dimensional diffusion of substrates to the catalytic sites may be achieved by the electrostatically negative ACP swinging to each of the six electrostatically positive catalytic sites. The phosphopantetheinyl transferase domain lies outside the shell of the assembly, inaccessible to ACP that lies inside, suggesting that the attachment of the pantetheine arm to ACP must occur before complete assembly of the complex. << Less

  Cell 129:319-332(2007) [PubMed] [EuropePMC]

• Yeast fatty acid synthetase: structure-function relationship and nature of the beta-ketoacyl synthetase site.

  Stoops J.K., Wakil S.J.

  Yeast fatty acid synthetase consists of two multifunctional proteins, alpha and beta, which are arranged in a complex of alpha(6)beta(6). Electron microscopic studies of this complex led to a model for the synthetase as an ovate structure consisting of an equatorial plate-like structure to which s ... >> More

  Yeast fatty acid synthetase consists of two multifunctional proteins, alpha and beta, which are arranged in a complex of alpha(6)beta(6). Electron microscopic studies of this complex led to a model for the synthetase as an ovate structure consisting of an equatorial plate-like structure to which six arches are equally distributed on either side. The bifunctional reagent 1,3-dibromo-2-propanone inhibits the synthetase by reacting rapidly (t((1/2)) approximately 7 sec) with two juxtapositioned active sulfhydryl groups. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the dibromopropanone-inhibited synthetase shows that the beta subunit is intact and the alpha subunit nearly absent with a concomitant appearance of oligomers with an estimated molecular weight of 0.4-1.2 x 10(6). These results indicate that the alpha subunits are crosslinked by this bifunctional reagent. Because the active centers of dibromopropanone are 5 A apart, it is concluded that the alpha subunits are closely packed so that the reacting thiols of the adjacent alpha subunits are within 5 A of each other. Furthermore, because the plate-like structures in our model are the only components that are arranged closely enough to satisfy this requirement, it is proposed that the alpha subunits are the "plates" and the beta subunits therefore are the "arches." Assay of the partial reactions shows that dibromopropanone inhibits the beta-ketoacyl synthetase reaction but none of the six other partial reactions, indicating that the site of action of the bifunctional reagent is the condensing reaction. This conclusion was supported by the finding that pretreatment of the synthetase with acetyl-CoA or iodoacetamide prevented dibromopropanone from interacting at this site and obviated the formation of the crosslinked oligomer. These observations and other lead us to propose that a site of action of the dibromopropanone is the active cysteine-SH of the beta-ketoacyl synthetase of one alpha subunit and the pantetheine-SH of the acyl carrier protein moiety of an adjacent alpha subunit. Thus, the enzymically active center of the beta-ketoacyl synthetase consists of an acyl group attached to the cysteine-SH of one alpha subunit (plate) and a malonyl group attached to the pantetheine-SH of an adjacent alpha subunit. This arrangement appears to be necessary for the coupling of the acyl and beta-carbon of the malonyl group to occur to yield CO(2) and the beta-ketoacyl product. << Less

  Proc Natl Acad Sci U S A 77:4544-4548(1980) [PubMed] [EuropePMC]

• Studies on the yeast fatty acid synthetase. Subunit composition and structural organization of a large multifunctional enzyme complex.

  Stoops J.K., Awad E.S., Arslanian M.J., Gunsberg S., Wakil S.J., Oliver R.M.

  J Biol Chem 253:4464-4475(1978) [PubMed] [EuropePMC]

• Pantetheine-free mutants of the yeast fatty-acid-synthetase complex.

  Schweizer E., Kniep B., Castorph H., Holzner U.

  Eur J Biochem 39:353-362(1973) [PubMed] [EuropePMC]