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Pathway Description
Palmitate Biosynthesis
Escherichia coli
Metabolic Pathway
Palmitate is synthesized by stepwise condensation of C2 units to a growing acyl chain. Each elongation cycle results in the addition of two carbons to the acyl chain, and consists of four separate reactions.
The pathway starts with acetyl-CoA interacting with hydrogen carbonate through an ATP driven acetyl-CoA carboxylase resulting in a phosphate, an ADP , a hydrogen ion and a malonyl-CoA. The latter compound interacts with a holo-[acp] through a malonyl-CoA-ACP transacylase resulting in a CoA and a malonyl-[acp]. This compound interacts with hydrogen ion, acetyl-CoA through a KASIII resulting in a CoA, carbon dioxide and an acetoacetyl-[acp].
The latter compound interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (R) 3-Hydroxybutanoyl-[acp](1).
This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a crotonyl-[acp](2).
The crotonyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a butyryl-[acp](3).
The butyryl-[acp] interacts with a hydrogen ion, a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-hexanoyl-[acp](4).
The 3-oxo-hexanoyl-[acp] interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (R) 3-Hydroxyhexanoyl-[acp](1).
This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans hex-2-enoyl-[acp](2).
The trans hex-2-enoyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a hexanoyl-[acp](3).
The hexanoyl-[acp] interacts with a hydrogen ion, a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-octanoyl-[acp](4).
The 3-oxo-octanoyl-[acp] interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (R) 3-Hydroxyoctanoyl-[acp](1).
This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans oct-2-enoyl-[acp](2).
The trans oct-2-enoyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a octanoyl-[acp](3).
The octanoyl-[acp] interacts with a hydrogen ion, a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-decanoyl-[acp](4).
The 3-oxo-decanoyl-[acp] interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (R) 3-Hydroxydecanoyl-[acp](1).
This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans-delta2-decenoyl-[acp](2).
The a trans-delta2-decenoyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a decanoyl-[acp](3).
The decanoyl-[acp] interacts with a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-dodecanoyl-[acp](4).
The 3-oxo-dodecanoyl-[acp ]interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (R) 3-Hydroxydodecanoyl-[acp](1).
This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans dodec-2-enoyl-[acp](2).
The trans dodec-2-enoyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a dodecanoyl-[acp](3). This compound can either react with water spontaneously resulting in a hydrogen ion, a holo-[acp] and a dodecanoic acid or it interacts with a hydrogen ion, a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-myristoyl-[acp](4).
The 3-oxo-myristoyl-[acp] interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (3R) 3-Hydroxymyristoyl-[acp](1).
This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans tetradec-2-enoyl-[acp](2).
This compound interacts with a hydrogen ion, through a NADH-driven KASI resulting in a NAD and a myristoyl-[acp].
Myristoyl-[acp] with a hydrogen ion, a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-palmitoyl-[acp](4).
The 3-oxo-palmitoyl-[acp] interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (3R) 3-Hydroxypalmitoyl-[acp](1).
This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans hexadecenoyl-[acp](2).
The trans hexadecenoyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a palmitoyl-[acp](3).
Palmitoyl then reacts with water spontaneously resulting in a hydrogen ion, a holo-[acp] and palmitic acid.
No integral membrane protein required for long chain fatty acid uptake has been identified in E. coli. The transport of long chain fatty acids across the cytoplasmic membrane is dependent on fatty acyl-CoA synthetase. An energised membrane is necessary for fatty acid transport and it has been suggested that uncharged fatty acids flip across the inner membrane by diffusion.
References
Palmitate Biosynthesis References
Zhang L, Joshi AK, Smith S: Cloning, expression, characterization, and interaction of two components of a human mitochondrial fatty acid synthase. Malonyltransferase and acyl carrier protein. J Biol Chem. 2003 Oct 10;278(41):40067-74. doi: 10.1074/jbc.M306121200. Epub 2003 Jul 25.
Pubmed: 12882974
White SW, Zheng J, Zhang YM, Rock: The structural biology of type II fatty acid biosynthesis. Annu Rev Biochem. 2005;74:791-831. doi: 10.1146/annurev.biochem.74.082803.133524.
Pubmed: 15952903
Pollard MR, Anderson L, Fan C, Hawkins DJ, Davies HM: A specific acyl-ACP thioesterase implicated in medium-chain fatty acid production in immature cotyledons of Umbellularia californica. Arch Biochem Biophys. 1991 Feb 1;284(2):306-12.
Pubmed: 1989513
Miinalainen IJ, Chen ZJ, Torkko JM, Pirila PL, Sormunen RT, Bergmann U, Qin YM, Hiltunen JK: Characterization of 2-enoyl thioester reductase from mammals. An ortholog of YBR026p/MRF1'p of the yeast mitochondrial fatty acid synthesis type II. J Biol Chem. 2003 May 30;278(22):20154-61. doi: 10.1074/jbc.M302851200. Epub 2003 Mar 24.
Pubmed: 12654921
Jeon E, Lee S, Won JI, Han SO, Kim J, Lee J: Development of Escherichia coli MG1655 strains to produce long chain fatty acids by engineering fatty acid synthesis (FAS) metabolism. Enzyme Microb Technol. 2011 Jun 10;49(1):44-51. doi: 10.1016/j.enzmictec.2011.04.001. Epub 2011 Apr 8.
Pubmed: 22112270
Ferguson DJ, Campbell SA, Henriquez FL, Phan L, Mui E, Richards TA, Muench SP, Allary M, Lu JZ, Prigge ST, Tomley F, Shirley MW, Rice DW, McLeod R, Roberts CW: Enzymes of type II fatty acid synthesis and apicoplast differentiation and division in Eimeria tenella. Int J Parasitol. 2007 Jan;37(1):33-51. doi: 10.1016/j.ijpara.2006.10.003. Epub 2006 Oct 30.
Pubmed: 17112527
Chan DI, Vogel HJ: Current understanding of fatty acid biosynthesis and the acyl carrier protein. Biochem J. 2010 Aug 15;430(1):1-19. doi: 10.1042/BJ20100462.
Pubmed: 20662770
Azizan A, Black PN: Use of transposon TnphoA to identify genes for cell envelope proteins of Escherichia coli required for long-chain fatty acid transport: the periplasmic protein Tsp potentiates long-chain fatty acid transport. J Bacteriol. 1994 Nov;176(21):6653-62.
Pubmed: 7961418
Mangroo D, Gerber GE: Photoaffinity labeling of fatty acid-binding proteins involved in long chain fatty acid transport in Escherichia coli. J Biol Chem. 1992 Aug 25;267(24):17095-101.
Pubmed: 1512247
Schmelter T, Trigatti BL, Gerber GE, Mangroo D: Biochemical demonstration of the involvement of fatty acyl-CoA synthetase in fatty acid translocation across the plasma membrane. J Biol Chem. 2004 Jun 4;279(23):24163-70. doi: 10.1074/jbc.M313632200. Epub 2004 Apr 2.
Pubmed: 15067008
Weimar JD, DiRusso CC, Delio R, Black PN: Functional role of fatty acyl-coenzyme A synthetase in the transmembrane movement and activation of exogenous long-chain fatty acids. Amino acid residues within the ATP/AMP signature motif of Escherichia coli FadD are required for enzyme activity and fatty acid transport. J Biol Chem. 2002 Aug 16;277(33):29369-76. doi: 10.1074/jbc.M107022200. Epub 2002 May 28.
Pubmed: 12034706
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from PW000797
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