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Glycolysis for Microbiome Generation

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  • Author: Alan J. Wolfe1
  • Editors: Tyrrell Conway2, Paul Cohen3
    Affiliations: 1: Department of Microbiology and Immunology, Stritch School of Medicine, Health Sciences Division, Loyola University Chicago, Maywood, Illinois; 2: Oklahoma State University, Stillwater, OK; 3: University of Rhode Island, Kingston, RI
  • Source: microbiolspec June 2015 vol. 3 no. 3 doi:10.1128/microbiolspec.MBP-0014-2014
  • Received 09 January 2015 Accepted 14 January 2015 Published 11 June 2015
  • Alan J. Wolfe, [email protected]
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  • Abstract:

    For a generation of microbiologists who study pathogenesis in the context of the human microbiome, understanding the diversity of bacterial metabolism is essential. In this chapter, I briefly describe how and why I became, and remain, interested in metabolism. I then will describe and compare some of the strategies used by bacteria to consume sugars as one example of metabolic diversity. I will end with a plea to embrace metabolism in the endeavor to understand pathogenesis.

  • Citation: Wolfe A. 2015. Glycolysis for Microbiome Generation. Microbiol Spectrum 3(3):MBP-0014-2014. doi:10.1128/microbiolspec.MBP-0014-2014.


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For a generation of microbiologists who study pathogenesis in the context of the human microbiome, understanding the diversity of bacterial metabolism is essential. In this chapter, I briefly describe how and why I became, and remain, interested in metabolism. I then will describe and compare some of the strategies used by bacteria to consume sugars as one example of metabolic diversity. I will end with a plea to embrace metabolism in the endeavor to understand pathogenesis.

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Acetyl-coenzyme A (AcCoA) is the keystone molecule of central metabolism. Glucose is metabolized via the EMP pathway to AcCoA in an NAD-dependent manner. The AcCoA is interconverted with amino acids and fatty acids. It replenishes the NAD-dependent tricarboxylic acid (TCA) cycle. It is the substrate for most secondary metabolites and the acetyl donor for some lysine acetylations, such as the PAT-dependent acetylation of ACS (acCoA synthetase). Acetate dissimilation requires the Pta-AckA pathway. The enzyme PTA (phosphotransacetylase) converts AcCoA and inorganic phosphate (P) into coenzyme A (CoA) and the high-energy pathway intermediate AcP. AcP donates its phosphoryl group to certain two-component response regulators (RR). AcP also can donate its acetyl group to hundreds of proteins. The enzyme ACKA (acetate kinase) converts AcP and ADP to acetate and ATP. The acetate freely diffuses across the cell envelope into the environment. Acetate assimilation requires the high-affinity enzyme ACS. In a two-step process that involves an enzyme-bound intermediate (acAMP), Acs converts acetate, ATP, and CoA into AMP, pyrophosphate (PP), and acCoA. ACS activity is inhibited by acetylation of a conserved lysine catalyzed by the lysine acetyltransferase (PAT, also known as YfiQ and Pka). Reactivation is catalyzed by the NAD-dependent deacetylase CobB. Adapted from Hu et al., 2010. GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PDH, pyruvate dehydrogenase.

Source: microbiolspec June 2015 vol. 3 no. 3 doi:10.1128/microbiolspec.MBP-0014-2014
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Three substrate-level phosphorylations. The first two examples are steps in the lower half of the EMP pathway. The third is a step in acetate fermentation.

Source: microbiolspec June 2015 vol. 3 no. 3 doi:10.1128/microbiolspec.MBP-0014-2014
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Glycolysis in and related bacteria. The Embden-Meyerhoff-Parnas (EMP), the Pentose Phosphate (PP), and Entner-Doudoroff (ED) pathways. The boxes highlight reactions unique to the PP and ED pathways. When glucose is metabolized by the EMP, the lower half of the pathway is repeated twice. In and related bacteria, glucose is transported and phosphorylated using PEP as the phosphoryl donor. Thus, one of the two PEP molecules generated by the EMP pathway is used to transport and phosphorylate another glucose molecule. For the PP pathway to function, two glucose molecules must be metabolized. Pentose sugars and sugar acids can be metabolized via the PP and ED pathways, respectively. PEP, phosphoenol pyruvate; PFK, phosphofructokinase; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; EDD, 6-phosphogluconate dehydratase; EDA, 2-keto 3-deoxy-D-gluconate 6-phosphate aldolase.

Source: microbiolspec June 2015 vol. 3 no. 3 doi:10.1128/microbiolspec.MBP-0014-2014
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Fermentation. A) General strategy, B) Homolactic acid fermentation, and C) Ethanol fermentation.

Source: microbiolspec June 2015 vol. 3 no. 3 doi:10.1128/microbiolspec.MBP-0014-2014
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A mixed-acid fermentation. Blue steps consume NAD, whereas red steps recycle NAD. Green compounds are excreted. GAP, glyceraldehyde 3-phosphate; PEP, phosphoenol pyruvate; HSCoA, coenzyme A; P, inorganic phosphate.

Source: microbiolspec June 2015 vol. 3 no. 3 doi:10.1128/microbiolspec.MBP-0014-2014
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The heterolactic pathway. EC 4.1.29 is a phosphoketolase that cleaves a 5-carbon phosphosugar (xylulose 5-phosphate) into a 3-carbon phosphate (glyceraldehyde 3-phosphate) and a 2-carbon phosphate (acetyl phosphate). Note that all the NAD-consuming steps are balanced by NAD-producing steps. Because acetyl phosphate is used to recycle NAD, it is not used to generate ATP.

Source: microbiolspec June 2015 vol. 3 no. 3 doi:10.1128/microbiolspec.MBP-0014-2014
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The Bifidobacterium shunt. Xfp is a bifunctional phosphoketolase. One activity (EC cleaves a 6-carbon phosphosugar (fructose 6-phosphate) into a 4-carbon phosphate (erythrose 4-phosphate) and a 2-carbon phosphate (acetyl phosphate). A second activity (EC 4.1.29) cleaves a 5-carbon phosphosugar (xylulose 5-phosphate) into a 3-carbon phosphate (glyceraldehyde 3-phosphate) and a 2-carbon phosphate (acetyl phosphate). Note that all the NAD-consuming steps are balanced by NAD-producing steps. Acetyl phosphate is used to generate ATP.

Source: microbiolspec June 2015 vol. 3 no. 3 doi:10.1128/microbiolspec.MBP-0014-2014
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