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Category: Bacterial Pathogenesis
Glycolysis for Microbiome Generation, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818883/9781555818869_Chap01-1.gif /docserver/preview/fulltext/10.1128/9781555818883/9781555818869_Chap01-2.gifAbstract:
There is no life without metabolism. There is nothing surprising about this statement; it is blatantly obvious and true for both host and bacteria, whether commensal or pathogen. What is surprising is the delayed general recognition that metabolism plays a, or perhaps, the central role in pathogenesis, which is simply a manifestation of the need for certain “bad” bacteria to grow and divide on or in a host. Perhaps this delay is natural, as researchers tend to focus on particularities, in this case, cellular processes unique to pathogenesis. Another reason for this delay is likely the aversion of late 20th Century microbiologists, who came to science after the heyday of bacterial metabolic research and who were forced to memorize whole swaths of the metabolic chart, usually out of context and with little understanding of the intricate linkages between metabolic pathways and their connections to other cellular processes.
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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 (Pi) 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 (PPi), 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.
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.
Glycolysis in E. coli 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 E. coli 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.
Fermentation. A) General strategy, B) Homolactic acid fermentation, and C) Ethanol fermentation.
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; Pi, inorganic phosphate.
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.
The Bifidobacterium shunt. Xfp is a bifunctional phosphoketolase. One activity (EC 4.1.2.22) 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.