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Category: Bacterial Pathogenesis
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 Helicobacter pylori cells both by nuclear magnetic resonance (NMR) and spectrophotometric assays. In Escherichia coli 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 Helicobacter species has revealed some characteristic features of the Helicobacter 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 acpS in H. pylori.
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Citric acid cycle and related reactions in H. pylori. 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.
Citric acid cycle and related reactions in H. pylori. 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.
Predicted pathways for fatty acid and phospholipid biosynthesis in H. pylori. 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 fabG, A, I, and F. It is noteworthy that no fabA homolog has been identified in H. pylori, which in E. coli 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 plsB, which catalyzes the first acylation of glycerol-3-phosphate, has not been identified. The function and ORF numbers of the H. pylori 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.
Predicted pathways for fatty acid and phospholipid biosynthesis in H. pylori. 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 fabG, A, I, and F. It is noteworthy that no fabA homolog has been identified in H. pylori, which in E. coli 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 plsB, which catalyzes the first acylation of glycerol-3-phosphate, has not been identified. The function and ORF numbers of the H. pylori 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.
Genomic and biochemical evidence for CAC enzymes in H. pyloria
Genomic and biochemical evidence for CAC enzymes in H. pyloria
Summary of genes associated with fatty acid synthesis in H. pylori
Summary of genes associated with fatty acid synthesis in H. pylori