Introduction to Metabolism

What is Metabolism?

• Metabolism comes from the Greek word metabolē, which means "transition" or "change".
• Metabolism involves all life-sustaining chemical reactions in living organisms.
• These reactions maintain the living state of the cells and the organism.
• Metabolism requires energy, carbon, and other vital nutrients.

Metabolism Fueling Reactions

• A range of organic substrates become ATP, reducing power, and precursor metabolites through metabolism.
• ATP provides energy conservation.
• Reducing power provides electrons for chemical reactions.
• Precursor metabolites provide carbon skeletons for biosynthesis.

Catabolism vs Anabolism

• Catabolism involves breaking down molecules and conserving energy often in the form of ATP.
• Anabolism involves synthesizing macromolecules, such as proteins, nucleic acids, carbohydrates, and complex lipids.
• Anabolism assembles these macromolecules into cell components.

Broad Summary of Metabolism:

• Energy sources are chemoorganotrophs, chemolithotrophs and phototrophs
• Carbon sources are autotrophs and heterotrophs
• Electron sources are organotrophs and lithotrophs
• These fuel catabolism to make ATP:
  • ATP then allows for anabolism where carbon atoms assemble into bigger macro molecules

Chemoheterotrophic Fueling Pathways

• Processes like respiration and fermentation break down organic molecules to store ATP
• In respiration, organic energy and an electron source go through glycolysis, then the electron transport chain to produce ATP
• In fermentation, an organic energy and electron source donates electrons to endogenous electron acceptors, resulting in ATP and fermentation products

ATP as Energy Carrier

• ATP releases energy when its bond is broken

Aerobic Respiration

• Polysaccharides go to monosaccharides
• Proteins go to amino acids
• Lipids go to Glycerol and Fatty acids
• The above all convert to Acetyl-CoA
• Acetyl-CoA enters the tricarboxylic acid cycle (Krebs cycle)
• The final result will be for the NADH, FADH molecules to go through the Electron Transport Chain to create ATP

Energy Metabolism Concept

• Nutrients go through catabolism to make ATP
• That ATP then fuels anabolism

Electron Carriers

• Redox reactions involve molecules gaining or losing electrons.
• Reduction potential signifies a substance's electron donating or accepting tendency.
• A more negative reduction potential indicates a stronger reducing agent.
• A more positive reduction potential indicates a stronger oxidizing agent.

Free Energy from Redox Reactions

• The formula E: NAD+/NADH = -0.32 V
• The formula E: 1/2 O2/H2O = 0.815 V
• The formula ΔE′0 = 1.14 V
• The formula ∆G°' = −nF.ΔE
• The formula AGº′ = −2 * 96 485 (J/V.mol) * 1.14V = −219 kJ (−52.1 kcal)

Electron Transport Chain

• Electrons are harvested and carried to the transport system.
• These electrons provide energy to pump protons across the membrane.
• Oxygen joins with protons to form water

The Breakdown of Glucose to Pyruvic Acid

• Glucose goes through the Embden-Meyerhof-Parnas, Entner-Doudoroff, or the Pentose Phosphate pathway, then converts to pyruvic acid
• The above occurs in the cytoplasm

The Embden-Meyerhof-Parnas pathway:

• Glucose + 2ADP + 2Pi + 2NAD+ results in 2Pyruvic acid + 2ATP + 2NADH + 2H+

Amphibolic Pathway

• Amphibolic pathways are metabolic pathways that are reversible

Entner-Doudoroff pathway:

• Glucose + ADP + NADP+ + NAD+ result in 2 pyruvate + ATP + NADPH + NADH + 2H+

Pentose-Phosphate Pathway

• Glucose-6-phosphate+ 12NADP+ + 7H2O results in 6CO₂ + 12NADPH + 12H+ + Pi
• NADPH plays a role in biosynthesis.
• Erythrose 4-P is aromatic amino acids, Vit. B6
• Ribose 5-P is a Major component of nucleic acids
• Intermediates used for ATP synthesis, e.g. glyceraldehyde 3-P

Summary of Three Glucose Pathways

• Embden-Meyerhof (EM) pathway: Glucose + 2ADP + 2Pi + 2NAD+ results in 2 pyruvate + 2ATP + 2NADH + 2H+
• Pentose phosphate (PP) pathway: Glucose-6-P + 12NADP+ + 7H₂O results in 6CO₂ + 12NADPH + 12H+ + Pi
• Entner-Doudoroff (ED) pathway: Glucose + ADP + Pi + NADP+ + NAD+ results in 2 pyruvate + ATP + NADPH + NADH + 2H+

The Tricarboxylic Acid Cycle

• This is also known as the Krebs or Citric Acid cycle
• Pyruvate catabolism to CO₂ occurs, and involves more energy (NADH & ATP) than EMP

Electron Transport Chain (ETC)

• It is a series of electron carriers that transfer electrons from donors (NADH, FADH2) to acceptors (O2)
• The ETC involves electrons flowing from complexes with more negative reduction potentials to complexes with more positive reduction potentials.

ATP Yield

• The formula NADH + H+ + 3ADP + 3Pi + 1⁄2O₂ → NAD+ + 3АТР + H₂O
• NADH: P/O ratio = 3
• FADH₂: P/O ratio= 2

Energy Balance

• Glycolysis produces 2 NADH for the electron transport chain; Net 2 ATP are from substrate level phosphorylation
• Balance for 3 NADH & 1 FADH2
• Decarboxylation of pyruvate produces 1NADH and 1CO2
• Combined results of the above is 1Glucose + 38ADP+ 38Pi + 6O₂ → 2Pyruvate + 38ATP + 44H₂O + 6CO₂

Chemiosmotic Hypothesis

• Chemiosmosis is the movement of protons across s selectively-permeable membrane, down their electrochemical gradient.
• ATP is generated by the movement of hydrogen ions across a membrane during cellular respiration.

Electron Transport Chain Inhibitors

• Cyanide, antimycin and sodium azide and are inhibitors
• Uncouplers
• Protons leak across the membrane, bypassing ATP synthase
• Dinitrophenol

ATP Yield - Prokaryotes

• Eukaryotes typically yield more ATP than Prokaryotes
• P/O Ratio between 0.67 and 1.3

Anaerobic Respiration

• In anaerobic respiration, substances other than oxygen act as the electron acceptor

Fermentation

• In fermentation, organic energy and an electron source donate electrons to endogenous electron acceptors

Fermentation :Alcoholic fermentation

• In alcoholic fermentation, CO₂ coverts to NADH
• Which turns into Acetaldehyde and converts NADH to Ethanol

Ethanol Production by Bakers' Yeast

• Bakers' yeast undergoes the Crabtree effect and the Pasteur effect
• It consists of Saccharomyces cerevisiae (Bakers' yeast / Brewers' yeast)
• It consists of the process of respiro-fermentative metabolism and Oxido-reductive metabolism

Glyoxylate Pathway:

• A modified Krebs cycle is used as the glyoxylate pathway.
• It is used to replenish intermediates and is used to generate intermediates for biosynthesis when ethanol and acetate are used as carbon sources when ethanol and acetate are used as carbon sources

Degradation of Fatty Acids

• It requires the aerobic process
• Occurs in the mitochondrial cytoplasm
• Breakdown of recalcitrant molecules such as alkanes is possible

Biosynthesis if Fatty Acids

• Occurs in the cytoplasm
• Fatty acids are determined by the number of synthesis cycles

Gluconeogenesis

• Glucose-6-P can be produced from a variety of products as lactic acid, fatty acids and amino acids through biosynthesis, or gluconeogenesis, which is essentially glycolysis in reverse.
• In gluconeogenesis, pyruvate is converted to phosphoenolpyruvate via a C4-compound intermediate (oxaloacetic acid)