Cellular Repsiration (MITOCHONDRIA)

• Cellular respiration in the mitochondria is an exergonic multistep metabolic pathway.

  • exergonic means energy producing.

• in cellular respiration organic molecules are oxidized and disassembled by a series of enzymes

  • energy is used to synthesize ATP (endergonic process)

  • endergonic means using energy

• Oxygen is REQUIRED for maximum ATP production

What Is Glucose?

• glucose is an energy-rich moleulce with many C-C, C-H, C-O bonds.

• energy is within the Carbon bonds

Glucose Oxidation

1. glycolysis occurs in cytosol and does not require oxygen.

2. intermediate stage

3. citric acid cycle

4. electron transport system (Stages 2, 3, & 4) occurs in mitochondria and requires oxygen.

Net Chemical Reaction

• C6H12O2 + 6O2 → 6CO2 + 6H2O

• broken bond energy attaches phosphorus to ADP

  • Direct it the least common

    • substrate level phosphorylation

  • indirect is the most common and energy is first release to coenzymes to form ATP

    • oxidative phosphorylation

Glycolysis

• glycolysis is a metablic process that occurs in cytosol not requiring oxygen where glucose is the intial substrate and pyruvate is the final product.

  • glycolysis produces 2 ATP and uses 4 ATP where the net production of ATP is 2.

• during glycolysis 2 NADH is formed.

• negative feedback regulates glycolysis where ATP acts as allosteric inhibitor to turn of PFK

  • increase ATP to inhibit PFK

• pyruvate strictly depends on oxygen

  • high level of oxygen means pyruvate can enter mitochondria

  • low levels of oxygen means pyruvate is converted into lactate

Intermediate Stage

• intermediate stage is where pyruvate releases CO2, NADH+ produces NADH and changes coenzyme A into acetyl CoA.

• Occur in mitochondria, double-membrane organelle (cristae), outer compartment, matrix.

  • cristae are inner membrane folds where molecules of electron transport system are embedded

  • outer compartment is that space between membranes

  • matrix is the innermost space that houses the multienzyme complex & citric acid cycle enzymes

Citric Acid Cycle

• step 1: Acetyl CoA combined with oxaloacetate to form citrate

• steps 2 & 3: Isomer formed by removing water molecule, then reattaching elsewhere

• steps 4 & 5: Transfer of hydrogen to NAD+ to form NADH; CoA attached

• step 6: Removal of CoA and the formation of ATP

• step 7: Dehydrogenase transfers hydrogens to form FADH2

• step 8: water removed

• step 9: Dehydrogenase transfers hydrogen to form NADH

• regulation of citric acid cycles occurs at first stem enzyme citrate synthase.

  • high energy demands: Levels of NADH, ATP, and pathway intermediates low, Cycle activity increased

  • low energy demands: Levels of substances higher, Cycle activity decreases

• cyclic metabolic pathway involves nine enzymes in the mitochondrial matrix:

  • Acetyl CoA is converted to two CO2 molecules, CoA molecule released, and ATP, 3 NADH, and 1 FADH2 formed during one cycle.

Electron Transport System

• the electron transport system transfer electrons from NADH & FADH2. The energy is used to make ATP.

• e- transport system structures

  • in inner membrane (cristae)

  • H+ pump

  • Proteins that transport H+ from matrix to outer membrane compartment

  • Maintains a H+ gradient between outer compartment and mitochondrial matrix

  • Electron carriers

  • Transport electrons between H+ pumps

• e- transport system steps:

  1. electrons transferred from coenzymes to oxygen

  2. H+ gradient established

  3. H+ gradient harnessed to form ATP

• in oxidative phosphorylation oxygen is the final e- acceptor, ADP phosphorylation makes ATP, Distinguished from substrate-level phosphorylation:

  • substrate-level forms ATP from energy directly released from substrate

  • glycolysis & citric acid cycle

ATP Production

• in ATP production the number of molecules generated depends on entry point of electrons into the transport chain. Generates 2 ATP molecules.

  • Electrons from NADH pass through 3 H+ pumps and generates 3 ATP molecules

  • Electrons from FADH2 enter at second pump.

• ATP in glucose breakdown

• some ATP used during cellular respiration, so net ATP is 30 (may be slightly less due to enzymes)

Cyanide

• cyanide is a nitrogen triple-bonded with carbon, binds with a specific electron carrier of the electron transport system that inhibits e- transport system and ATP production.

  • electrons are unable to reach oxygen

Fate of Pyruvate

• pyruvate fate with low oxygen

  1. activity of electron transport chain decreases

     1. Levels of NADH and FADH2 accumulate, Decreased levels of NAD+ and FAD.

  2. cells become more dependent upon glycolysis

     1. requires NAD+ to continue

  3. glycolysis eventually shuts down

     1. due to lack of NAD+

  4. NAD+ must be regenerated for glycolysis to continue

NAD+ Regeneration

• NAD+ regeneration is when a hydrogen transferred from NADH to pyruvate, Pyruvate converted to lactate (lactic acid), Enables glycolysis to continue.

  • Only 2 ATP generated versus 30 with sufficient oxygen, Impacts individuals with decreased ability to deliver oxygen to cells (For example, those with respiratory or cardiovascular disease)

Other Oxidized Fuel Molecules

• Fatty acids enzymatically change two carbons at a time to form acetyl CoA (beta oxidation), Acetyl CoA the enters pathway at citric acid cycle, Can only be oxidized aerobically.

  • can be changed to sugars

• Amino acids have different pathway if protein is used for fuel, Point of entry depends upon specific type, Amine group is a waste product (Converted to urea, Excreted by kidneys)

• anything ending with -ase is an enzyme

What to Know?

• Glucose goes in, enzyme change the structure, break molecule apart into 2 G3P’s, NAD+ →NADH, 2ADP→ 2ATP, 2 pyruvate

• G3P (glyceraldehyde 3-phosphate)