Chapter 12 : The Citric Acid Cycle and Fatty Acid Biosynthesis

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The Citric Acid Cycle and Fatty Acid Biosynthesis, Page 1 of 2

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This chapter talks about fatty acid biosynthesis, linked to the citric acid cycle (CAC) through the utilization of acetyl-coenzyme A (CoA) as its starting point. The oxidative decarboxylation of pyruvate is an important reaction in archaea, bacteria, and eukaryotes alike, generating acetyl-CoA necessary for CAC reactions, fatty acid biosynthesis, and many other reactions requiring acyl-CoA. Citrate synthase catalyzes the first step in the oxidative branch of the CAC in which acetyl-CoA and oxaloacetate are condensed to generate citrate and CoA. Aconitase activity has been detected in the cytosolic fraction of cells both by nuclear magnetic resonance (NMR) and spectrophotometric assays. In isocitrate dehydrogenase acts as a critical branch point between the CAC reactions and the glyoxylate bypass during growth on C2 compounds like acetate. The study of the lipid and fatty acid profiles of eight species has revealed some characteristic features of the genus. Malonyl-acylcarrier protein (ACP) is required not only for initiation of fatty acid biosynthesis, but also for each subsequent round of elongation of the fatty acid chain. To function in fatty acid biosynthesis, the apo-ACP protein must first be activated by transfer of the 4'-phospho-pantotheine from CoA, and this reaction is predicted to be catalyzed by holo-ACP synthase, encoded by in .

Citation: Kelly D, Hughes N. 2001. The Citric Acid Cycle and Fatty Acid Biosynthesis, p 135-146. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch12

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Fatty Acid Biosynthesis
Fatty Acid Degradation
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Figure 1

Citric acid cycle and related reactions in Enzymes are denoted by numbers. 1, pyruvate:flavodoxin oxidoreductase; 2, phosphotransacetylase; 3, acetate kinase; 4, citrate synthase; 5, aconitase; 6, isocitrate dehydrogenase; 7, 2-oxoglutarate:acceptor oxidoreductase; 8, succinyl-CoA:acetoacetate CoA transferase; 9, NAD-linked malate dehydrogenase; 10, fumarase; 11, fumarate reductase; 12, malateiquinone oxidoreductase; 13, aspartase; 14, malate synthase. The mechanisms for anaplerotic oxaloacetate synthesis are unknown (thin dashed line). Fld, flavodoxin; Fd, ferredoxin. Solid lines indicate core CAC reactions, which have been demonstrated by enzyme assay. The thick dashed line for enzyme 8 indicates uncertainty about its physiological role.

Citation: Kelly D, Hughes N. 2001. The Citric Acid Cycle and Fatty Acid Biosynthesis, p 135-146. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch12
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Figure 2

Predicted pathways for fatty acid and phospholipid biosynthesis in During the initiation phase of fatty acid biosynthesis, acetyl-CoA is carboxylated to generate malonyl-CoA, which is then converted to malonyl-ACP. Malonyl-ACP is also required for each subsequent round of elongation. Several potential pathways for the formation of acetoacetyl-ACP are described in the text; for simplicity, only the condensation of acetyl-CoA and malonyl-ACP by FabH is illustrated. Acetoacetyl-ACP is then used as a substrate for the elongation reactions encoded by and It is noteworthy that no homolog has been identified in which in acts as the branch point for unsaturated fatty acid synthesis. The acyl-ACP generated by FabI may enter another round of elongation through condensation with malonyl-ACP or act as a substrate for phospholipid biosynthesis. A homolog of the glycerol-3-phosphate acyltransferase enzyme, encoded by which catalyzes the first acylation of glycerol-3-phosphate, has not been identified. The function and ORF numbers of the H. genes shown in this diagram are summarized in Table 2. Genes that have not been identified in the genome sequence are identified with an asterisk.

Citation: Kelly D, Hughes N. 2001. The Citric Acid Cycle and Fatty Acid Biosynthesis, p 135-146. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch12
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1. Aim, R. A.,, L.-S. Lee,, D. T. Moir,, B. L. King,, E. D. Brown,, P. C. Doig,, D. R. Smith,, B. Noonan,, B. C. Guild,, B. L. de Jonge,, G. Carmel,, P. J. Tummino,, A. Caruso,, M. Uria-Nickelson,, D. M. Mills,, C. Ives,, R. Gibson,, D. Merberg,, S. D. Mills,, Q. Jiang,, D. E. Taylor,, G. F. Vovis,, and T. J. Trust. 1999. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397:176180.
2. Beil, W.,, C. Birkholz,, S. Wagner,, and K. F. Sewing. 1994. Interaction of Helicobacter pylori and its fatty acids with parietal cells and gastric H+/K( + )-ATPase. Gut 35:11761180.
3. Birkholz, S.,, U. Knipp,, E. Lemma,, A. Kroger,, and W. Opferkuch. 1994. Fumarate reductase of Helicobacter pylori—an immunogenic protein. J. Med. Microbiol. 41:5662.
4. Blarney, J. M.,, and M.W. Adams. 1993. Purification and characterization of pyruvate:ferredoxin oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus. Biochim. Biophys. Acta 1161:1927.
5. Blarney, J. M.,, and M. W. Adams. 1994. Characterization of an ancestral type of pyruvate:ferredoxin oxidoreductase from the hyperthermophilic bacterium. Thermotoga maritima. Biochemistry 33:10001007.
6. Burns, B. P.,, S. L. Hazell,, and G. L. Mendz. 1995. Acetyl-CoA carboxylase in Helicobacter pylori and the requirement for increased CO2 for growth. Microbiology 141:31133118.
7. Chalk, P. A.,, A. D. Roberts,, and W. M. Blows. 1994. Metabolism of pyruvate and glucose by intact cells of H. pylori studied by 13C-NMR spectroscopy. Microbiology 140:20852092.
8. Chang, H. T.,, S. W. Marcelli,, A. A. Davison,, P. A. Chalk,, R. K. Poole,, and R.J. Miles. 1995. Kinetics of substrate oxidation by whole cells and cell membranes of Helicobacter pylori. FEMS Microbiol. Lett. 129:3338.
9. Charbriere, E.,, M. Charon,, A. Volbeda,, L. Pieulle,, E. Hatchikian,, and J. Fontecilla-Camps. 1999. Crystal structure of the key anaerobic enzyme pyruvate:ferredoxin oxidoreductase, free and in complex with pyruvate. Nat. Struct. Biol. 6:182190.
10. Cordwell, S. J. 1999. Microbial genomes and "missing" enzymes: redefining biochemical pathways. Arch. Microbiol. 172:269279.
11. Corthesy-Theulaz, I. E.,, G. E. Bergonzelli,, H. Hemry,, D. Bach-mann,, D. F. Schorderet,, A. L. Blum,, and L. N. Ornston. 1997. Cloning and characterization of Helicobacter pylori succinyl CoA: acetoacetate CoA-transferase, a novel prokaryotic member of the CoA-transferase family. J. Biol. Chem. 272: 2565925667.
12. Cunningham, L.,, M. J. Gruer,, and J. R. Guest. 1997. Transcriptional regulation of the aconitase genes (acnA and acnB) of Escherichia coli. Microbiology 143:37953805.
13. Davison, A. A.,, D. J. Kelly,, P. J. White,, and P. A. Chalk. 1993. Citric-acid cycle enzymes and respiratory metabolism in H. pylori. Acta Gastro-Enterol. Belg. 56S:96.
14. Docampo, R.,, S. N. J. Moreno,, and R. P. Mason. 1987. Free radical intermediates in the reaction of pyruvate:ferredoxin oxidoreductase in Tritrichomonas foetus hydrogenosomes. J. Biol. Chem. 262:1241712420.
15. Dunkley, M. L.,, S. J. Harris,, R. J. McCoy,, M. J. Musicka,, F. M. Eyers,, L. G. Beagley,, P. J. Lumley,, K. W. Beagley,, and R. L. Clancy. 1999. Protection against Helicobacter pylori infection by intestinal immunization with a 50/52-kDa subunit protein. FEMS Immunol. Med. Microbiol. 24:221225.
16. Ge, Z. Q.,, and D. E. Taylor. 1997. The Helicobacter pylori gene encoding phosphatidylserine synthase: sequence, expression, and insertional mutagenesis. J. Bacteriol. 179: 49704976.
17. Ge, Z.,, Q. Jiang,, M. S. Kalisiak,, and D. E. Taylor. 1997. Cloning and functional characterization of Helicobacter pylori fumarate reductase operon comprising three structural genes coding for subunits C, A and B. Gene 204:227234.
18. Haque, M.,, Y. Hirai,, K. Yokota,, N. Mori,, I. Jahan,, H. Ito,, H. Hotta,, I. Yano,, Y. Kanemasa,, and K. Oguma. 1996. Lipid profile of Helicobacter spp.: presence of cholesteryl glucoside as a characteristic feature. J. Bacteriol. 178:20652070.
19. Heath, R. J.,, and C. O. Rock. 1999. A missense mutation accounts for the defect in the glycerol-3-phosphate acyltransferase expressed in the plsB26 mutant. J. Bacteriol. 181:19441946.
20. Hirai, Y.,, M. Haque,, T. Yoshida,, K. Yokota,, T. Yasuda,, and K. Oguma. 1995. Unique cholesteryl glucosides in Helicobacter pylori: composition and structural analysis. J. Bacteriol. 177:53275333.
21. Hoffman, P. S.,, A. Goodwin,, J. Johnsen,, K. Magee,, and S. J. O. Veldhuzyen van Zanten. 1996. Metabolic activities of metronidazole-sensitive and resistant strains of Helicobacter pylori: repression of pyruvate oxidoreductase and expression of isocitrate lyase activity correlate with resistance.J. Bacteriol. 178:48224829.
22. Hughes, N. J.,, P. A. Chalk,, C. L. Clayton, and D. J. Kelly. 1995. Identification of carboxylation enzymes and characterization of a novel four subunit pyruvate:flavodoxin oxidoreductase from Helicobacter pylori. J. Bacteriol. 177: 39533959.
23. Hughes, N. J.,, C. L. Clayton,, P. A. Chalk,, and D. J. Kelly. 1998. Helicobacter pylori porCDAB and oorDABC genes encode distinct pyruvate:flavodoxin and 2-oxoglutarate:acceptor oxidoreductases which mediate electron transport to NADP. J. Bacteriol. 180:11191128.
24. Huynen, M. A.,, T. Dandekar,, and P. Bork. 1999. Variation and evolution of the citric-acid cycle: a genomic perspective. Trends Microbiol. 7:281291.
25. Ingeldew, W. J.,, and R. K. Poole. 1984. The respiratory chains of Escherichia coli. Microbiol. Rev. 48:222271.
26. Kaihovaara, P.,, J. Hook-Nikanne,, M. Uusi-Oukari,, T. U. Kosunen,, and M. Salaspuro. 1998. Flavodoxin-dependent pyruvate oxidation, acetate production and metronidazole reduction by Helicobacter pylori. J. Antimicrob. Chemother. 41:171177.
27. Kather, B.,, K. Stingl,, M. E. van der Rest,, K. Altendorf,, and D. Molenaar. 2000. Another unusual type of citric-acid cycle enzyme in Helicobacter pylori: the malate:quinone oxidoreductase. J. Bacteriol. 182:32043209.
28. Kelly, D. J. 1998. The physiology and metabolism of the human gastric pathogen Helicobacter pylori. Adv. Microb. Physiol. 40:137189.
29. Kerscher, L.,, and D. Oesterhelt. 1981. Purification and properties of two 2-oxoacid:ferredoxin oxidoreductases from Halobacterium halobium Eur.. J. Biochem. 116:587594.
30. Kerscher, L.,, and D. Oesterhelt. 1981. The catalytic mechanism of 2-oxoacid:ferredoxin oxidoreductases from Halobacterium halobium. Eur. J. Biochem. 116:595600.
31. Knappe, J.,, and G. Sawers. 1990. A radical-chemical route to acetyl-CoA: the anaerobically induced pyruvate formate-lyase system of Escherichia coli. FEMS Microbiol. Rev. 6:383398.
32. Kroger, A.,, V. Geisler,, E. Lemma,, F. Theis,, and R. Lenger. 1992. Bacterial fumarate respiration. Arch. Microbiol. 158: 311314.
33. LaPorte, D. C.,, and T. Chung. 1985. A single gene codes for the kinase and phosphatase which regulates isocitrate dehydrogenase. J. Biol. Chem. 260:1529115297.
34. Larson, T. J.,, D. N. Ludtke,, and R. M. Bell. 1984. sra-Glycerol-3-phosphate auxotrophy of plsB strains of E. coli: evidence that a second mutation, plsX, is required. J. Bacteriol. 160: 711717.
35. Lichtenberger, L. M.,, S. L. Hazell,, J. J. Ramero,, and D. Y. Graham. 1990. Helicobacter pylori hydrolysis of artificial lipid monolayers: insight into a potential mechanism of mucosal injury. Gastroenterology 98:A78.
36. McAtee, C. P.,, K. E. Fry,, and D. E. Berg. 1998. Identification of potential diagnostic and vaccine candidates of Helicobacter pylori by "proteome" technologies. Helicobacter 3:163169.
37. Meinecke, B.,, J. Bertram,, and G. Gottschalk. 1989. Purification and characterization of the pyruvate-ferredoxin oxidoreductase from Clostridium acetobutylicum. Arch. Microbiol. 152:244250.
38. Mendz, G. L.,, and S. L. Hazell. 1993. Fumarate catabolism in Helicobacter pylori. Biochem. Mol. Biol. Int. 31:325332.
39. Mendz, G. L.,, and S. L. Hazell. 1995. Aminoacid utilization by Helicobacter pylori. Int. J. Biochem. Cell. Biol. 27: 10851093.
40. Mendz, G. L.,, S. L. Hazell,, and S. Srinivasan. 1995. Fumarate reductase: a target for therapeutic intervention against Helicobacter pylori. Arch. Biochem. Biophys. 321:153159.
41. Narindrasorasak, S.,, A. H. Goldie,, and B. D. Sanwal. 1979. Characteristics and regulation of a phospholipid-activated malate oxidase from Escherichia coli. J. Biol. Chem. 254: 15401545.
42. Ottlecz, A.,, J. J. Romero,, S. L. Hazell,, D. Y. Graham,, and L. M. Lichtenberger. 1993. Phospholipase activity of Helicobacter pylori and its inhibition by bismuth salts. Biochem. Biophys. Res. Commun. 38:20712080.
43. Patel, M. S.,, and T. E. Roche. 1990. Molecular biology and biochemistry of pyruvate dehydrogenase complexes. FASEB J. 4:32243233.
44. Pieulle, L.,, M. H. Charon,, P. Bianco,, J. Bonicel,, Y. Petillot,, and E. C. Hatchikian. 1999. Structural and kinetic studies of the pyruvate-ferredoxin oxidoreductase/ferredoxin complex from Desulfovibrio africanus. Eur. J. Biocbem. 264:500508.
45. Pieulle, L.,, B. Guigliarelli,, M. Asso,, F. Dole,, A. Bernadec,, and E. C. Hatchikian. 1995. Isolation and characterization of the pyruvate-ferredoxin oxidoreductase from the sulfate reducing bacteria Desulfovibrio africanus. Biochim. Biophys. Acta 1250:4959.
46. Pitson, S. M.,, G. L. Mendz,, S. Srinivasan,, and S. L. Hazell. 1999. The tricarboxylic acid cycle of Helicobacter pylori. Eur. J. Biocbem. 260:258267.
47. Rock, C. O.,, and J. E. Cronan. 1996. Escherichia coli as a model for the regulation of dissociable (type II) fatty acid biosynthesis. Biochim. Biophys. Acta 1302:116.
48. Rosenthal, B.,, Z. Mai,, D. Caplivski,, S. Ghosh,, H. de la Vega,, T. Graf,, and J. Samuelson. 1997. Evidence for the bacterial origin of genes encoding fermentation enzymes of the amito-chondriate protozoan parasite Entamoeba histolytica. J. Bacteriol. 179:37363745.
49. Shah, V. K.,, G. Stacey,, and W.J. Brill. 1983. Electron transport to nitrogenase: purification and characterization of pyruvate: flavodoxin oxidoreductase, the nifj gene product. J. Biol. Cbem. 258:1206412068.
50. Smith, E. T.,, J. M. Blarney,, and M. W. Adams. 1994. Pyruvate ferredoxin oxidoreductases of the hyperthermophilic archaeon, Pyrococcus furiosus and the hyperthermophilic bacterium Thermatoga maritima have different catalytic mechanisms. Biochemistry 33:10081016.
51. Spiro, S.,, and J. R. Guest. 1991. Adaptive responses to oxygen limitation in Escherichia coli. Trends Biochem. Sci. 61: 310314.
52. Tersteegen, A.,, D. Linder,, R. K. Thauer,, and R. Hedderich. 1997. Structures and functions of four anabolic 2-oxoacid oxidoreductases in Methanobacterium thermoautotrophicum. Eur. J. Biochem. 244:862868.
53. Tomb, J.-F.,, O. White,, A. R. Kerlavage,, R. A. Clayton,, G. G. Sutton,, R. D. Fleishmann,, K. A. Ketchum,, H. P. Klenk,, S. Gill,, B. Dougherty,, K. Nelson,, J. Quackenbush,, L. Zhou,, E. F. Kirkness,, S. Peterson,, B. Loftus,, D. Richardson,, R. Dodson,, H. G. Khalak,, A. Glodek,, K. McKenney,, L. M. Fitzegerald,, N. Lee,, M. D. Adams,, E. Hickey,, D. E. Berg,, J. D. Gocayne,, T. R. Utterback,, J. D. Peterson,, J. M. Kelley,, M. D. Cotton,, J. M. Weidman,, C. Fujii,, C. Bowman,, L. Watthey,, E. Wallin,, W. S. Hayes,, M. Borodovsky,, P. D. Karp,, H. O. Smith,, C. M. Fraser,, and J. C. Venter. 1997. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388: 539547.
54. Weitkamp, H. J. H.,, G. I. Perez-Perez,, G. Bode,, P. Malfertheiner,, and M. J. Blaser. 1993. Identification and characterization of Helicobacter pylori phospholipase C activity. Int. J. Med. Microbiol. Virol. Parisitol. Infect. Dis. 280:1127.
55. Williams, K.,, P. N. Lowe,, and P. F. Leadlay. 1987. Purification and characterization of pyruvate ferredoxin oxidoreductase from the anaerobic protozoan Trichomonas vaginalis. Biochem. J. 246:529536.


Generic image for table
Table 1

Genomic and biochemical evidence for CAC enzymes in

Citation: Kelly D, Hughes N. 2001. The Citric Acid Cycle and Fatty Acid Biosynthesis, p 135-146. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch12
Generic image for table
Table 2

Summary of genes associated with fatty acid synthesis in

Citation: Kelly D, Hughes N. 2001. The Citric Acid Cycle and Fatty Acid Biosynthesis, p 135-146. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch12

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