Microbial Oxidation of Glycollate Via A Dicarboxylic Acid Cycle

Kornberg, H. L.; Sadler, J. R.

doi:10.1038/185153a0

Cited by 45 publications

(26 citation statements)

References 21 publications

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“…A somewhat similar cycle was described in E. coli during growth on two-carbon compounds that involved also PEP carboxykinase and malate synthase (35). Because this dicarboxylic acid cycle does not contain isocitrate lyase and citrate synthase, it is specific for the oxidation of compounds that are metabolized via glyoxylate.…”

Section: Discussionmentioning

confidence: 93%

A Novel Metabolic Cycle Catalyzes Glucose Oxidation and Anaplerosis in Hungry Escherichia coli

Fischer

Sauer

2003

Journal of Biological Chemistry

181

172

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Complete oxidation of carbohydrates to CO 2 is considered to be the exclusive property of the ubiquitous tricarboxylic acid cycle, the central process in cellular energy metabolism of aerobic organisms. Based on metabolism-wide in vivo quantification of intracellular carbon fluxes, we describe here complete oxidation of carbohydrates via the novel P-enolpyruvate (PEP)-glyoxylate cycle, in which two PEP molecules are oxidized by means of acetyl coenzyme A, citrate, glyoxylate, and oxaloacetate to CO 2 , and one PEP is regenerated. Key reactions are the constituents of the glyoxylate shunt and PEP carboxykinase, whose conjoint operation in this bi-functional catabolic and anabolic cycle is in sharp contrast to their generally recognized functions in anaplerosis and gluconeogenesis, respectively. Parallel operation of the PEP-glyoxylate cycle and the tricarboxylic acid cycle was identified in the bacterium Escherichia coli under conditions of glucose hunger in a slow-growing continuous culture. Because the PEPglyoxylate cycle was also active in glucose excess batch cultures of an NADPH-overproducing phosphoglucose isomerase mutant, one function of this new central pathway may be the decoupling of catabolism from NADPH formation that would otherwise occur in the tricarboxylic acid cycle.Structuring of cellular networks into pathways with distinct functions is pivotal for comprehension of "textbook" biochemistry. The ability of existing model pathways to portray flux through complex metabolic networks, however, is an open question that is just beginning to be addressed theoretically (1-3) and experimentally (4, 5). Microbial growth on the most abundant carbon-source glucose represses transcription of metabolic functions that are required on alternative carbon sources. This universal phenomenon is referred to as catabolite repression and includes a number of mechanistically distinguishable but physiologically related regulation mechanisms (6, 7). Although catabolite repression is strong under conditions of feast with excess glucose, microbes typically thrive under conditions of starvation (absence of nutrients) or hunger (suboptimal supply of nutrients) in their natural environments (8,9). This metabolic state of hunger, between optimal growth and starvation, can be studied in glucose-limited continuous (chemostat) cultures with very low glucose concentrations at a rate of growth that is controlled by the experimenter. Catabolite repression is absent under the severe glucose limitation in slow growing chemostat cultures (9 -11), and, as a consequence, increased in vivo activity of repressed metabolic enzymes is often observed with advanced methods of metabolic flux analyses based on 13 C-labeling experiments (4, 5, 12, 13).Here we elucidate metabolic impacts of severe and absent catabolite repression during growth of Escherichia coli in glucose-excess batch cultures and glucose-limited chemostat cultures. Direct analytical interpretation of 13 C-labeling patterns in proteinogenic amino acids was used to establish the ...

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Section: Discussionmentioning

confidence: 93%

A Novel Metabolic Cycle Catalyzes Glucose Oxidation and Anaplerosis in Hungry Escherichia coli

Fischer

Sauer

2003

Journal of Biological Chemistry

181

172

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“…Jack and I were able to show that the provision of energy from glycolate could occur via a dicarboxylic acid cycle, in which an isoform of malate synthetase catalyzed the condensation of glyoxylate and acetyl-coenzyme A as the first step in a sequence of reactions that led from malate via oxaloacetate and pyruvate to the loss of two carbons as CO 2 and to the reformation of the acetyl-coenzyme A acceptor (34). Measurement of the levels of citrate and malate synthetases during growth on acetate or glycolate dramatically illustrated the relative roles of the TCA and dicarboxylic acid cycles in the oxidation of these C 2 compounds (24) and lent confidence to the view that this latter cycle might, under the right circumstances, actually be physiologically significant (35).…”

Section: The Oxford Yearsmentioning

confidence: 99%

Memoirs of a Biochemical Hod Carrier

Kornberg

2003

Journal of Biological Chemistry

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“…Whole peptonegrown organisms cannot oxidize added glyoxylate ( Table 2). If glycine is oxidized to glyoxylate as is likely (Kornberg & Sadler, 1960), a block at glyoxylate could explain the inadequacy of glycine as a single nutrient. The fact that some growth did occur on glycine is probably explained by the 'catalytic' activity of amino acids from the intracellular pool, and these amino acids also undoubtedly contributed to the high rate of endogenous respiration.…”

Section: Discussionmentioning

confidence: 99%

Some Properties of a Gram-Negative Heterotrophic Marine Bacterium

Brown

1960

Journal of General Microbiology

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SUMMARYSome properties of a marine bacterium are described. This organism belongs to a large, but ill-defined, group comprising Gram-negative rods with no apparent action on monosaccharides. It is a polar flagellate, has limited acid tolerance, consistent with its inability to produce acid from sugars and has no constitutive system for metabolizing glucose. A weak inducible system was available, however, which enabled adapted organisms to grow on glucose and use it as a respiratory substrate. The organism also lacks a constitutive citric acid cycle but ability to metabolize succinate was induced by growth on succinate or glucose. It cannot use inorganic nitrogen for growth. Of the compounds examined, amino acids were the most generally satisfactory sources of energy, carbon, and nitrogen. The organism accumulated a relatively large pool of intracellular amino acids which probably contributed largely to its high rate of endogenous respiration. The classification of the bacterium is discussed.

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Microbial Oxidation of Glycollate Via A Dicarboxylic Acid Cycle

Cited by 45 publications

References 21 publications

A Novel Metabolic Cycle Catalyzes Glucose Oxidation and Anaplerosis in Hungry Escherichia coli

A Novel Metabolic Cycle Catalyzes Glucose Oxidation and Anaplerosis in Hungry Escherichia coli

Memoirs of a Biochemical Hod Carrier

Some Properties of a Gram-Negative Heterotrophic Marine Bacterium

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