Glycolysis, Krebs Cycle, and other Energy-Releasing Pathways

All organisms produce ATP by releasing energy stored in glucose and other sugars.

• Plants make ATP during photosynthesis.
• All other organisms, including plants, must produce ATP by breaking down molecules such as glucose

Aerobic respiration - the process by which a cell uses O₂ to "burn" molecules and release energy

The reaction: C₆H₁₂O₆ + 6O₂ >> 6CO₂ + 6H₂O

Note: this reaction is the opposite of photosynthesis

This reaction takes place over the course of three major reaction pathways

• Glycolysis
• The Krebs Cycle
• Electron Transport Phosphorylation (chemiosmosis)

Glycolysis (glyco = sugar; lysis = breaking)

• Goal: break glucose down to form two pyruvates
• Who: all life on earth performs glyclolysis
• Where: the cytoplasm
• Glycolysis produces 4 ATP's and 2 NADH, but uses 2 ATP's in the process for a net of 2 ATP and 2 NADH

NOTE: this process does not require O₂ and does not yield much energy

• Glucose (6C) is broken down into 2 PGAL's (Phosphoglyceraldehyde - 3Carbon molecules)
• This requires two ATP's

• 2 PGAL's (3C) are converted to 2 pyruvates
• This creates 4 ATP's and 2 NADH's
• The net ATP production of Glycolysis is 2 ATP's

Oxidation of Pyruvate and the Krebs Cycle (citric acid cycle, TCA cycle)

• Goal: take pyruvate and put it into the Krebs cycle, producing NADH and FADH₂
• Where: the mitochondria
• There are two steps
  • The Conversion of Pyruvate to Acetyl CoA
  • The Krebs Cycle proper
• The Krebs cycle and the conversion of pyruvate to Acetyl CoA produce 2 ATP's, 8 NADH's, and 2FADH₂'s per glucose molecule

• 2 NADH's are generated (1 per pyruvate)
• 2 CO₂ are released (1 per pyruvate)

• 6 NADH's are generated (3 per Acetyl CoA that enters)
• 2 FADH₂ is generated (1 per Acetyl CoA that enters)
• 2 ATP are generated (1 per Acetyl CoA that enters)
• 4 CO₂'s are released (2 per Acetyl CoA that enters)

  

   

• Therefore, the total numbers of molecules generated in the oxidation of pyruvate and the Krebs Cycle is:
  • 8 NADH
  • 2 FADH₂
  • 2 ATP
  • 6 CO₂

• Goal: to break down NADH and FADH₂, pumping H⁺ into the outer compartment of the mitochondria
• Where: the mitochondria
• In this reaction, the ETS creates a gradient which is used to produce ATP, quite like in the chloroplast
• Electron Transport Phosphorylation typically produces 32 ATP's
• ATP is generated as H+ moves down its concentration gradient through a special enzyme called ATP synthase

• Glycolysis: 2 ATP
• Krebs Cycle: 2 ATP
• Electron Transport Phosphorylation: 32 ATP
  • Each NADH produced in Glycolysis is worth 2 ATP (2 x 2 = 4) - the NADH is worth 3 ATP, but it costs an ATP to transport the NADH into the mitochondria, so there is a net gain of 2 ATP for each NADH produced in gylcolysis
  • Each NADH produced in the conversion of pyruvate to acetyl COA and Krebs Cycle is worth 3 ATP (8 x 3 = 24)
  • Each FADH₂ is worth 2 ATP (2 x 2 = 4)
  • 4 + 24 + 4 = 32
• Net Energy Production: 36 ATP!

Anaerobic Respiration

• Goal: to reduce pyruvate, thus generating NAD⁺
• Where: the cytoplasm
• Why: in the absence of oxygen, it is the only way to generate NAD⁺

• Alcohol Fermentation - occurs in yeasts in many bacteria
  • The product of fermentation, alcohol, is toxic to the organism

• Lactic Acid Fermentation - occurs in humans and other mammals
  • The product of Lactic Acid fermentation, lactic acid, is toxic to mammals
  • This is the "burn" felt when undergoing strenuous activity

• The only goal of fermentation reactions is to convert NADH to NAD⁺ (to use in glycolysis).
• No energy is gained
• Note differences - anaerobic respiration - 2 ATP's produced (from glycolysis), aerobic respiration - 36 ATP's produced (from glycolysis, Krebs cycle, and Oxidative Phosphorylation)
• Thus, the evolution of an oxygen-rich atmosphere, which facilitated the evolution of aerobic respiration, was crucial in the diversification of life

Photosynthesis: 6 CO₂ + 6 H₂O >> C₆H₁₂O₆ + 6 O₂

Respiration: C₆H₁₂O₆ + 6 O₂ >> 6 CO₂ + 6 H₂O

Notice that these reactions are opposites - this is important since the earth is a closed system

All life has a set amount of natural materials to work with, so it is important that they all be cycled through effectively and evenly

Energy Yields:

• Glucose: 686 kcal/mol
• ATP: 7.5 kcal/mol
• 7.5 x 36 = 270 kcal/mol for all ATP's produced
• 270 / 686 = 39% energy recovered from aerobic respiration

Related Catabolic Processes - Beta Oxidation

• Fats consist of a glycerol backbone with two or three fatty acids connected to it
• The body absorbs fats and then breaks off the fatty acids from the glycerol
• Glycerol is converted to glyceraldehyde phosphate, an intermediate of glycolysis
• The fatty acids are broken down into two-carbon units which are then converted to acetyl CoA.
  • An eight-carbon fatty acid can produce 4 acetyl CoA's
  • Each acetyl CoA is worth 12 ATP's (3 NADP, 1 FADH₂, 1 ATP)
  • Therefore, this short fatty acid is worth 48 ATP's, a fat with three chains of this length would be worth 144 ATP's!
  • This is why fats are such a good source of energy, and are hard to lose if you want to lose weight

A comparison between Plants and Animals

• Animal cells and Plant cells contain mitochondria!
  • However, animal cells contain many more mitochondria than plant cells
• Animal cells get most of their ATP from mitochondria
• Plant cells get most of their ATP from the chloroplast
  • The ATP generated from the mitochondria is only used when the plant cannot generate ATP directly from the light-dependent reactions

Other Uses for Molecules used in Glycolysis and the Krebs Cycle

• Not all of the molecules that enter Glycolysis and the Krebs Cycle are used for energy
• Some are used to synthesize fats, nucleotides, amino acids, and other biologically important molecules.

Regulation of Glycolysis and the Krebs Cycle

• Step 3 of Glycolysis - The conversion of Fructose 6-phosphate to Fructose 1,6-bisphosphate
  • Enzyme catalyzing this reaction =  Phosphofructokinase
  • "Committing Step"  - Fructose 6-phosphate can be used by the cell for lots of things, but fructose 1,6-bisphosphate has limited  use except in glycolysis
  • Phosphofructokinase inhibited by high levels of ATP
    • ATP is also a substrate - odd, eh? 
    • Enzyme has two ATP binding sites, one in the active site and one in an allosteric site
    • Low to mid levels of ATP cause ATP to bind to the active site
    • High levels of ATP also enable ATP to bind to allosteric site, causing a conformation change and shutting down the enzyme
• Conversion of Pyruvate to Acetyl CoA
  • Enzyme involved in catalyzing this reaction = pyruvate dehydrogenase
  • High levels of ATP slow down this reaction by phosporylating the enzyme, changing its shape and shutting it down
    • High levels of NADH and Acetyl CoA also inhibit this enzyme
  • NAD+, CoA, or AMP (an indicator of low ATP) can speed up the reaction