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Microbial Metabolism: Chemical Reactions, Pathways, and Regulation

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Microbial Metabolism

Introduction to Metabolism

Microbial metabolism encompasses all the controlled biochemical reactions that occur within a microorganism. These reactions are essential for acquiring nutrients, generating energy, synthesizing macromolecules, and supporting growth and reproduction.

  • Metabolism: The sum of all chemical reactions in a cell.

  • Metabolic processes are guided by eight key statements, including nutrient acquisition, energy generation and storage, macromolecule synthesis, and cell growth and division.

Overview of catabolism and anabolism in a cell

Basic Chemical Reactions

Catabolism and Anabolism

Metabolic reactions are divided into two major classes: catabolism and anabolism.

  • Catabolic pathways: Break down larger molecules into smaller products, releasing energy (exergonic). Some energy is stored as ATP, while most is lost as heat. Catabolism produces precursor metabolites for anabolism.

  • Anabolic pathways: Synthesize large molecules from smaller products of catabolism, requiring energy input (endergonic). Energy is supplied by ATP hydrolysis or sunlight.

Oxidation and Reduction (Redox) Reactions

Redox reactions involve the transfer of electrons from an electron donor to an electron acceptor. These reactions are fundamental to energy transfer in cells.

  • Oxidation: Loss of electrons, hydrogen atoms, or gain of oxygen atoms.

  • Reduction: Gain of electrons or hydrogen atoms.

  • Redox reactions always occur simultaneously (OIL RIG: Oxidation Is Loss, Reduction Is Gain).

Redox reaction: electron transfer between donor and acceptorDehydrogenation and reduction of NAD+ to NADH

  • Cells use electron carriers such as NAD+, NADP+, and FAD to shuttle electrons during metabolic reactions.

Adenosine Triphosphate (ATP)

ATP is the primary energy currency of the cell, capturing and transferring chemical energy released during catabolism.

  • ATP consists of adenine, ribose, and three phosphate groups.

  • Hydrolysis of ATP releases energy by removing phosphate groups, converting ATP to ADP or AMP.

Structure of ATP and its high-energy phosphate bondsHydrolysis of ATP to ADP and energy release

Phosphorylation Mechanisms

Cells regenerate ATP from ADP by phosphorylation, which can occur via three mechanisms:

Type

Source of Phosphate

Source of Energy

Location in Eukaryotes

Location in Prokaryotes

Substrate-level phosphorylation

Organic molecule

High-energy phosphate from substrate

Cytosol, mitochondria

Cytosol

Oxidative phosphorylation

Inorganic phosphate (Pi)

Proton motive force

Inner mitochondrial membrane

Cytoplasmic membrane

Photophosphorylation

Inorganic phosphate (Pi)

Light energy (proton motive force)

Thylakoid of chloroplast

Thylakoid of cyanobacteria membrane

Comparison of the three types of phosphorylation

Enzymes and Catalysis

Enzymes are biological catalysts that speed up chemical reactions by lowering activation energy without being consumed. Most enzymes are proteins, but some RNA molecules (ribozymes) also have catalytic activity.

  • Enzymes are specific to their substrates and reactions.

  • Enzyme names often end in -ase and reflect their substrate or function.

Class

Type of Reaction Catalyzed

Examples

Hydrolases

Hydrolysis (addition of water)

Lipase, protease

Isomerases

Rearrangement of atoms

Phosphoglucoisomerase

Ligases/Polymerases

Joining molecules

DNA ligase, RNA polymerase

Lyases

Splitting without water

Aldolase

Oxidoreductases

Redox reactions

Lactic acid dehydrogenase

Transferases

Transfer functional groups

Hexokinase

Enzyme classification based on reaction types

Enzyme Structure and Function

Many enzymes require nonprotein cofactors (inorganic ions or organic coenzymes) for activity. The combination of an apoenzyme (protein) and its cofactor forms a holoenzyme (active enzyme).

Structure of a holoenzyme with cofactors

Cofactor

Example of Use

Substance Transferred

Vitamin Source

Inorganic (Metal ion)

Iron in ATP synthesis

Phosphate

None

NAD+

Carrier of reducing power

Two electrons, hydrogen ion

Niacin (B3)

NADP+

Carrier of reducing power

Two electrons, hydrogen ion

Niacin (B3)

FAD

Carrier of reducing power

Two hydrogen atoms

Riboflavin (B2)

Coenzyme A

Transfer of acetyl groups

Acetyl group

Pantothenic acid (B5)

Pyridoxal phosphate

Transfer of amino groups

Amino group

Pyridoxine (B6)

Representative cofactors of enzymes

Enzyme Activity and Regulation

Enzymes lower the activation energy required for reactions, increasing reaction rates. Their activity is influenced by temperature, pH, substrate concentration, and the presence of inhibitors.

Effect of enzymes on activation energy

  • Enzyme-substrate specificity is explained by the induced fit model.

Enzyme-substrate specificity (induced fit model)Process of enzymatic activity

  • Enzyme activity increases with temperature and substrate concentration up to an optimal point, after which denaturation or saturation occurs.

  • pH changes can also denature enzymes by disrupting hydrogen bonds.

Effects of temperature, pH, and substrate concentration on enzyme activityDenaturation of protein enzymes

  • Enzyme inhibitors can be competitive (bind active site) or noncompetitive (bind allosteric site).

Competitive inhibition of enzyme activityAllosteric control of enzyme activity

  • Feedback inhibition: End-product of a pathway inhibits an earlier enzyme, regulating pathway activity.

Feedback inhibition in metabolic pathwaysFeedback inhibition example with isoleucine

Carbohydrate Catabolism

Glycolysis

Glycolysis is the central pathway for glucose catabolism, occurring in the cytoplasm and producing pyruvate, ATP, and NADH.

  • Divided into three stages: energy-investment, lysis, and energy-conserving.

  • Net gain: 2 ATP, 2 NADH, 2 pyruvate per glucose.

Glycolysis: energy-investment and lysis stagesGlycolysis: energy-conserving stageSubstrate-level phosphorylation in glycolysis

Cellular Respiration

Cellular respiration is the complete oxidation of glucose to CO2 and H2O, generating ATP through glycolysis, the Krebs cycle, and the electron transport chain (ETC).

  • Synthesis of Acetyl-CoA: Pyruvate is decarboxylated and combined with CoA, producing acetyl-CoA, CO2, and NADH.

Formation of acetyl-CoA from pyruvate

  • Krebs Cycle: Acetyl-CoA enters the cycle, generating ATP, NADH, FADH2, and CO2.

The Krebs cycle

  • Electron Transport Chain (ETC): Electrons from NADH and FADH2 are transferred through a series of carriers, generating a proton gradient used to produce ATP via oxidative phosphorylation.

Electron transport chainArrangement of electron transport chain complexes

  • ATP Synthase: Enzyme complex that synthesizes ATP as protons flow down their gradient.

Structure and function of ATP synthase

  • Total ATP yield per glucose: ~38 in prokaryotes, ~36 in eukaryotes.

Summary of glucose catabolism

Alternative Pathways and Fermentation

Some microbes use alternative pathways for glucose catabolism or fermentation when oxygen is absent.

  • Pentose Phosphate Pathway: Generates NADPH and precursor metabolites for biosynthesis.

  • Entner-Doudoroff Pathway: Alternative to glycolysis, used by some bacteria.

Pentose phosphate pathwayEntner-Doudoroff pathway

  • Fermentation: Anaerobic process regenerating NAD+ for glycolysis, producing organic acids or alcohols as end products.

Fermentation pathwaysRepresentative fermentation products and organisms

Other Catabolic Pathways

Lipid and Protein Catabolism

Microbes can catabolize lipids and proteins for energy and precursor metabolites.

  • Lipases: Hydrolyze fats into glycerol and fatty acids. Fatty acids undergo beta-oxidation to form acetyl-CoA.

Catabolism of a fat molecule

  • Proteases: Break down proteins into amino acids, which are deaminated and converted into Krebs cycle intermediates.

Protein catabolism

Photosynthesis

Light-Dependent and Light-Independent Reactions

Photosynthetic organisms convert light energy into chemical energy, synthesizing carbohydrates from CO2 and H2O.

  • Chlorophylls: Pigments that capture light energy.

  • Photosystems: Complexes of chlorophyll and proteins embedded in membranes (thylakoids).

Photosynthetic structures in a prokaryote

  • Light-dependent reactions generate ATP and NADPH via cyclic and noncyclic photophosphorylation.

Cyclic and noncyclic photophosphorylation

  • Light-independent reactions (Calvin-Benson Cycle) use ATP and NADPH to fix carbon and synthesize glucose.

Calvin-Benson cycle

Other Anabolic Pathways

Gluconeogenesis, Lipogenesis, and Amino Acid Synthesis

Anabolic pathways synthesize complex molecules from simpler precursors, often reversing catabolic pathways.

  • Gluconeogenesis: Synthesis of glucose from noncarbohydrate sources.

  • Lipogenesis: Synthesis of fatty acids and triglycerides from acetyl-CoA.

  • Amino acid synthesis: Formation of amino acids via amination or transamination.

Role of gluconeogenesis in biosynthesisBiosynthesis of fat, a lipidAmination and transamination in amino acid synthesis

  • Nucleotide synthesis: Formation of nucleotides from glycolysis and Krebs cycle intermediates.

Biosynthesis of nucleotides

Integration and Regulation of Metabolic Function

Metabolic Regulation

Cells regulate metabolism to maximize growth and efficiency by controlling enzyme production, activity, and compartmentalization.

  • Regulation occurs at the level of gene expression and enzyme activity (allosteric regulation, feedback inhibition).

  • Cells preferentially use the most energy-efficient substrates and pathways available.

Integration of cellular metabolism

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