Cellular Respiration: Glycolysis and the Citric Acid Cycle

Glycolysis and Fermentation

• Second lecture focusing on cellular factories.
• Focus: Glycolysis, what happens with and without oxygen.
• In the presence of oxygen, glucose is broken down into carbon dioxide and water, extracting potential energy.

Metabolic Pathways

• Five main pathways occurring in different cell compartments, whether eukaryote or prokaryote.
• Eukaryotes:
  • Glycolysis and fermentation occur in the cytoplasm.
  • Citric acid cycle and other processes happen within the mitochondria.
• Prokaryotes:
  • Glycolysis and fermentation occur in the cytoplasm.
  • Citric acid cycle also happens in the cytoplasm.
  • Other processes occur on the membrane, between the membranes of the bacteria.

Glycolysis

• Splits (lyses) glucose.
• Converts glucose (six-carbon) into pyruvate (three-carbon).
• Produces a small amount of ATP (energy).
• Does not generate carbon dioxide because only splitting glucose, not dismantling it.
• Ten reactions in the glycolytic pathway.
  • First five steps: energy investing (require ATP to charge the glucose molecule).
  • Last five steps: energy yielding (produce more ATP and NADH).
  • NADH: electron carrier that captures electrons from the covalent bonds of the glucose molecule.
• Overall, glycolysis produces two molecules of pyruvate, two molecules of ATP, and two molecules of NADH.

Glycolysis Steps

• ATP invested at the beginning.
• Splitting into two three-carbon compounds, one of which is dihydroxyacetone phosphate.
• Dihydroxyacetone phosphate is converted into another molecule.
• Net gain of two ATP molecules overall.
• Substrate-level phosphorylation creates ATP from ADP.

Post-Glycolysis: Moving to the Mitochondria

• If intending to further break down pyruvate, it enters the mitochondria (if eukaryote) or cytoplasm (if prokaryote) for the citric acid cycle.
• Pyruvate is oxidized to acetate, forming acetyl CoA.
• Acetate is a two-carbon compound; carbon dioxide is released; NADH captures released energy from the electrons.
• Acetyl CoA is the starting point for the citric acid cycle.

Citric Acid Cycle (Krebs Cycle)

• Eight reactions in a cycle.
• Acetyl CoA and water is put in along with electron carriers NAD and FAD plus GDP.
• Releases a bit more of energy from the acetyl CoA originally from glucose.
• Energy captured in ATP (indirectly from GTP), NADH, and FADH2.
• Carbon dioxide is a byproduct.
• Dismantles the six-carbon glucose molecule bit by bit.

Citric Acid Cycle Reactions

• Pyruvate converted to acetyl CoA releases carbon dioxide and reduces NAD to NADH.
• The concentrations of intermediate compounds remain relatively constant because the cycle is in steady state. As one reaction proceeds it is passed to the next so on and so forth.
• Citric acid cycle is not literally a circle in the mitochondria; components are dispersed within the mitochondrial matrix.
• The point of the citric acid cycle is to release energy from the food molecules in the form of electron carriers as many high energy electrons as the cell can get.
• Two-carbon acetyl CoA + four-carbon oxaloacetate = six-carbon citrate (citric acid; where the name comes from).
• Citrate is decarboxylated twice, releasing more energy as electrons.
• The second half of reactions rearranges the structure to regenerate oxaloacetate, capturing more energy.
• Acetyl CoA can come from broken down fatty acids (two carbons at a time), in addition to sugars.
• Some intermediate molecules can be used to create other things the cell might need like amino acids.

Free Energy and Metabolic Processes

• Like a ball rolling down a hill.
• A little bit of energy like ATP is used to rearrange glucose into fructose with two negative phosphate groups which energizes the structure.
• Cannot take a glucose and cut it down the middle without adding energy.
• Splitting releases energy; electrons captured; more ATP made.
• Oxidizing pyruvate yields more electron carriers.
• Acetyl CoA enters the citric acid cycle and fully breaks down the ORIGINAL glucose.
• Each glucose = six carbon dioxides.
• 10 NADH and 2 FADH2 molecules plus ATP.
• If can fully break it down, glucose is an energy rich molecule.

Capturing Energy

• Captured high-energy electrons (NADH) pass on to another system.
• If no oxygen, fermentation reactions occur.
• If oxygen is present, oxidative phosphorylation occurs.
• Oxidative phosphorylation requires mitochondria and membranes (eukaryotes) or membranes in prokaryotic cells.
• Electrons captured in electron carriers passed to oxidative phosphorylation.

Oxidative Phosphorylation

• Production of ATP from ADP.
• Two stages: electron transport and chemiosmosis.
• Electron transport: electrons flow from carriers through a respiratory chain (proteins in a membrane).
• Electron flow pumps protons across the membrane to build a gradient.
• Occurs in mitochondria (eukaryotes) or inner membrane (prokaryotes).

Electron Transport Chain

• Two entry points for electron carriers.
• With NADH, electrons enter at complex one.
• Electrons are stripped from hydrogen, releasing them.
• Electrons pass through protein complexes to combine with oxygen, which acts as an electron acceptor and is why we need to breathe oxygen.
• FADH2 skips the first complex.
• Electron flow leads to protons being pumped across the membrane.
• A high proton gradient builds up across the inner membrane (high concentration in intermembrane space, low in the matrix).
• This is like a battery storing potential energy.

Chemiosmosis

• Protons flow back through ATP synthase (ATPase).
• It's chemi because there's a pH difference and acidicy in the intermembrane space.
• Membrane bound portion rotates like a turbine as protons attach and spin it.
• Physical rotational force induces conformational changes in the non-membrane bound portion.
• ADP and phosphate enter the active site, conformational change joins them to make ATP and kicks it out in a physical process.
• ATP synthase functions like a molecular turbine.

Dismantling Glucose Completely

• Glucose + Oxygen \rightarrow Carbon Dioxide + Water + Energy.
• Breakdown occurs in the presence of oxygen.
• Energy is extracted in tiny packets (electron carriers, ATP).
• The electron carriers pass on to the process to create lots of ATP.
• Traps free energy and uses it to make lots of ATP.