Bacterial Physiology (Micr430) Lecture 5 Central Pathways of Carbohydrate Metabolism (Text Chapter: 8)

Central Metabolic Pathways The central metabolic pathways are the pathways that provide the precursor metabolites to all the other pathways They are the pathways for the metabolism of carbohydrates and carboxylic acids. The major carbohydrate pathways: Embden-Meyerhof-Parnas (glycolysis or EMP) Pentose phosphate pathway (PPP) Entner-Doudoroff pathway (ED)

Embden-Meyerhof-Parnas Pathway This is also called Glycolysis or Fructose Bisphophate Aldolase Pathway Important reactions: Phosphorylation of glucose and fructose-6-phosphate by ATP Cleavage of fructose-1,6-bisphosphate to trioses by a specific aldolase Structural rearrangements Oxidation-reduction and Pi assimilation

EMP Pathway or Glycolysis Fig 8.2

EMP pathway The enzyme fructose bisphosphate aldolase is one of the most critical steps in the pathway In general, glycolysis in muscle tissue, yeast and many bacterial species are identical in terms of intermediates involved Pyruvate is the last common intermediate

Pentose Phosphate Pathway Significance of this pathway: It produces pentose phosphates – precursors to the ribose and deoxyribose in nucleic acids It produces erythrose phosphate – precursor to the aromatic amino acids NADPH is produced – major source of electrons for biosynthesis

Pentose Phosphate Pathway In this cycle, G-6-P is converted to ribulose-5-phosphate and CO2. Ribulose-5-phosphate is maintained in equilibrium with ribose-5-phosphate and xylulose-5-phosphate by isomerase and epimerase Through a series of transketolase and transaldolase reactions, three turns of cycle are required to produce one triose phosphate (plus 3 CO2) from one hexose

Pentose Phosphate Pathway Fig 8.11

Entner-Doudoroff Pathway This pathway is absence in eukaryotes This pathway is active in E. coli and many other Gram negative bacteria Two key enzymes: 6-phosphogluconate dehydratase (edd; reaction 2) and 2-keto-3-deoxy-6-phosphogluconate aldolase (eda; reaction 4)

Entner-Doudoroff Pathway Fig 8.12

Oxidation of Pyruvate to Acetyl-CoA Pyruvate is the common product of sugar catabolism in all major carbohydrate catabolic pathways One fate of pyruvate is to be oxidized to acetyl-CoA. During aerobic growth, this reaction is catalyzed by the enzyme complex pyruvate dehydrogenase

Oxidation of Pyruvate to Acetyl-CoA Pyruvate dehydrogenase from E. coli consists of 24 molecules of enzyme E1 (pyruvate dehydrogenase) 24 molecules of enzyme E2 (dihydrolipoate transacetylase) 12 molecules of enzyme E3 (dihydrolipoate dehydrogenase)

Pyruvate Dehydrogenase Complex Fig 8.14

TCA Cycle Tricarboxylic acid cycle also known as Krebs or citric acid cycle This is a cycle to generate remaining energy and reducing equivalents from end product of glycolysis, pyruvate Its intermediates serve as precursors for biosynthesis of many other important cellular compounds (amino acids)

TCA Cycle Fig 8.16

TCA Cycle under anaerobic conditions Under anaerobic conditions, TCA cycle cannot go full circle due to absence of terminal electron acceptor (O2) It now functions as a branched biosynthetic pathway: one branch operating as a reductive pathway reversing the sequence from succinate to oxaloacetate The other branch continuing to operate oxidatively to convert oxaloacetate to a-ketoglutarate

TCA variant under anaerobic condition

Glyoxylate Cycle Activation of acetate with CoA to form acetyl-CoA and the combined activities of the enzymes isocitritase (isocitrate lyase) and malate synthase provide for the operation of a C4 cycle called glyoxylate cycle It results in the net formation of malate from 2 mol of acetate Activity of this bypass cycle explains the ability of organisms to utilize acetate as a sole source of carbon for growth.

The Glyoxylate Cycle Fig 8.24