SUMMARY PARAGRAPH for FAS2
Fatty acids are essential components of eukaryotic and bacterial (but not archaeal) cells, where they are used in membrane synthesis, energy storage and protein modification. Most cells are capable of synthesizing, long chain saturated fatty acids de novo, using acetyl-CoA as a starting substrate. Fatty acid biosynthesis is essentially the same across organisms. In an iterative process, the growing fatty acid chain is gradually extended, two carbons at a time, until the final length is achieved. Each addition requires seven different catalytic activities as well as a pantetheinylated acyl-carrier protein, to which the growing fatty acid chain is attached (see fatty acid biosynthesis pathways: initial steps and elongation). In S. cerevisiae, palmitoleic (C16) and oleic (C18) acyl-CoAs are the most common products of this process. Although the biochemistry is similar across phylogeny, the physical organization of the catalytic sites varies between organisms. Plants, mitochondria and most bacteria have type II Fatty Acid Synthase (FAS II) systems, where each enzymatic activity is encoded by an individual, disassociated protein. Fungi, animals and some bacteria have type I Fatty Acid Synthase (FAS I) systems involving complexes of multifunctional proteins. In humans, for example, only the enzyme catalyzing the first step in fatty acid synthesis (the formation of malonyl-CoA by acetyl-CoA carboxylase, EC:22.214.171.124) is a separate protein; all other activities are contained within a single polypeptide, ACSL1, which forms an X-shaped homodimer complex (reviewed in 5, 6, 7, 8, 9).
In S. cerevisiae, as in humans, only the acetyl-CoA carboxylase activity (Acc1p) is separate. In contrast to humans, however, the other activities are distributed between two proteins, Fas1p and Fas2p, the beta and alpha subunits of a large, barrel-shaped complex containing 6 copies of each protein (alpha6beta6) (10, 11). Together, the six Fas1p and six Fas2p subunits form six independent reaction centers, each containing all enzyme activities required for synthesizing long chain fatty acids from acetyl- and malony-CoA (12, 13, and references therein). FAS1 encodes four independent enzymatic functions: acetyltransferase (EC:126.96.36.199), enoyl reductase (EC:188.8.131.52), dehydratase (EC:184.108.40.206), and malonyl/palmitoyl-transferase (EC:220.127.116.11) (14, 15, 16, 17). FAS2 encodes the acyl-carrier protein domain and three independent enzymatic functions: 3-ketoreductase (EC:18.104.22.168), 3-ketosynthase (EC:22.214.171.124) and phosphopantetheinyl transferase (EC:126.96.36.199) (14, 2, 3). This last enzymatic activity is not part of fatty acid biosynthesis, but rather is responsible for the pantetheinylation of the acyl-carrier protein domain (3 and references therein). This post-translational modification is essential for FAS I activity and is thought to allow movement of the growing fatty acid chain between the different catalytic sites in each reaction center. In humans, the phosphopantetheinyl transferase activity is catalyzed by a separate enzyme that is disassociated from the FAS I complex, AASDHPPT (9, 18 and references therein).
As "housekeeping" genes, FAS1 and FAS2 are constitutively activated by general transcription factors Rap1p, Abf1p, and Reb1p (19). Both FAS1 and FAS2 are further activated by the inositol/choline-responsive transcription factor heteroduplex, Ino2p-Ino4p (20, 21). In addition, Fas1p and Fas2p stoichiometry appears to be insured by a regulatory mechanism in which FAS1 protein controls FAS2 mRNA levels (22).
Last updated: 2010-04-24