Cellular Respiration

Cellular respiration breaks glucose molecules down and forms CO2 and water. The goal of cellular respiration is to trap the energy released by breaking down the glucose.

Cellular respiration occurs in four stages:
  1. Glycolysis - 10 steps in cytoplasm
  2. Pyruvate Oxidation - 1 step in mitochondrion matrix
  3. Krebs cycle - 8 steps in mitochondrion matrix
  4. Electron transport chain (oxidative phosphorylation) - multi-step in inner mitochondrion membrane
Throughout these four stages, energy is "removed" in one of two ways:
1) Substrate-level phophorylation: ATP is formed using enzymes
Used in: glycolysis, Krebs cycle
2) Oxidative phosphorylation: ATP is formed using redox reactions
Used in: e- transport chain (ETC)

STAGE 1 - Glycolysis

glucose +2 ATP 覧> 2 PGAL 覧> 2 pyruvate + 4 ATP

- occurs in cytoplasm;
- anaerobic (doesn't use oxygen);
- starts with glucose (6 carbon);
- the glucose is split into two 3 carbon pyruvate molecules;
- uses 2 ATP, produces 4 ATP and 2 NADH in the process.

Here are the 10 steps, in plain English. Follow the diagram:

GLUCOSE - 6 carbon:
1) In the cytoplasm, 1 ATP loses a phosphate and becomes ADP; the lost phosphate bonds to the glucose molecule
2) The altered glucose molecule is rearranged using isomerase, an enzyme
3) In the cytoplasm, another ATP becomes ADP and the phosphate bonds to the altered glucose molecule. By adding this phosphate, the glucose molecule is now symmetrical.
4) The altered glucose molecule is cut into two pieces called DHAP and PGAL. These two pieces are identical except for their shape.
5) Since it's the PGAL that is the right shape, DHAP is rearranged by isomerase until it has the same shape as PGAL. We now have two PGAL molecules.

PGAL (x2) - 3 carbon: (note: since there are two PGAL molecules, the following steps happen twice, once to each PGAL)
6) PGAL gains a phosphate but loses two hydrogen atoms. These hydrogen atoms bond to a NAD+ molecule in the cytoplasm, making it NADH. The NADH formed is used later in cellular respiration.
7) Now PGAL loses a phosphate; the phosphate bonds to an ADP molecule and forms ATP.
8, 9, 10) PGAL is rearranged and it loses H2O and a phosphate. The phosphate bonds to another ADP and forms ATP. The altered PGAL still has 3 carbons and is called pyruvate.

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STAGE 2 - Pyruvate Oxidation

pyruvate + CoA 覧> acetyl CoA

- occurs in matrix;
- uses the 2 pyruvate molecules from glycolysis and alters them;
- produces 2 acetyl-CoA molecules, 2 NADH and 2CO2; the CO2 is expelled.

Pyruvate oxidation happens twice for every glucose molecule because there were two pyruvate molecules produced in glycolysis. However, from now on we will follow the path of only 1 pyruvate.

There are only three steps to pyruvate oxidation:

PYRUVATE - 2 carbon:
1) CO2 is removed
2) 2 hydrogen atoms are removed from the pyruvate and they bond to NAD+ to form NADH
3) A coenzyme (CoA) is attached to the altered pyruvate. The new molecule is called acetyl-CoA and is used in the Krebs cycle, stage 3 if ATP levels are low; if ATP levels are high, acetyl-CoA is stored as fat

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STAGE 3: The Krebs Cycle

acetyl CoA + oxaloacetate 覧> 1 ATP + 3 NADH + FADH2 + 2CO2

- occurs in matrix;
- starts with acetyl-CoA + oxaloacetate, and ends with oxaloacetate; cycle repeats;
- 1 ATP, 3 NADH, FADH2 are produced;
- all the original glucose carbons are expelled as CO2.

There are 8 steps to the Krebs cycle:

ACETYL-CoA - 2 carbon:
1) Acetyl CoA reacts with oxaloacetate (4 carbon) to produce citric acid, because a 6 carbon molecule is needed to continue the Krebs cycle.
2) H2O is removed, the molecule is rearranged, and then H2O is replaced
3, 4) The molecule loses 2 CO2 molecules, and 4 hydrogen atoms. The hydrogen atoms are used to form 2 NADH molecules. Since 2 carbons were removed, the molecule now only has 4 carbons.
5) The molecule loses the CoA group (the coenzyme it picked up in stage 2), and ATP is formed.
6, 7, 8) The molecule loses 4 hydrogen atoms. These atoms are used to form FADH2 and NADH.

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STAGE 4: Electron transport chain
(oxidative phosphorylation)

NADH + FADH2 覧> e- + 2H+ 覧> ATP
This happens many times...)

- occurs in inner mitochondrion membrane;
- this is the stage where the most energy is produced;
- aerobic!!! without O2 the chain would get backlogged and stop working;
- electrons are passed down a chain of compounds called cytochromes, and energy is released. This energy is used to pump H+ ions into the intermembrane space;
- oxygen atoms remove the electrons when the electrons reach the final cytochrome;
- the H+ ions in the intermembrane space move back into the matrix by passing through an ATP synthase molecule. This creates ATP.

Here's how it works:

In the inner mitochondrion membrane there are many compounds called cytochromes. These compounds have the ability to attract electrons, but each specific compound has a different electronegativity. This means that cytochromes can only attract electrons at a certain energy level: some attract electrons that are at a high energy level, while others can only attract electrons that are at a low energy level.
The cytochromes are arranged in order of increasing electronegativity to form chains. The process begins when the first cytochrome gains 2 high-energy electrons. Once the electrons are within the first cytochrome, the energy level of the electrons is lowered, and the free energy is used to pump two H+ ions into the intermembrane space of the mitochondrion (see mitochondrion).
Now that the electrons are at a lower energy level, the second cytochrome is able to attract them. This lowers the energy of the electrons again, and releases free energy to pump two more H+ ions into the intermembrane space. The electrons are passed along the chain like this until they reach the last cytochrome. Here the low-energy electrons are removed by an oxygen atom.

The electrons used in the ETC are from electron carriers in the matrix: NADH and FADH2. The electrons that the two carriers carry are at slightly different energy levels, and so they enter the ETC at different points. The electrons of NADH enter at the first cytochrome, and so they are able to pump 3 pairs (6) H+ through, while the less energetic electrons of FADH2 enter at a later point in the chain and only pump 2 pairs (4) H+ ions through.

After a while, the concentration of H+ ions in the intermembrane space is much greater than the concentration in the matrix. Naturally, the H+ ions in the intermembrane space have a tendency to move to the less concentrated space in the matrix (THE SECOND LAW OF THERMODYNAMICS!), but to do that they must pass through an ATP synthase molecule. As the H+ ions pass through the ATP synthase, into the matrix, they lose energy. This free energy is enough to combine ADP + phosphate to produce ATP. Finally we have energy which the cell can use!

Because there was so much NADH and FADH2 produced in the first 3 stages of cellular respiration, the ETC chain produces a lot of ATP.

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SO.......... What's happened to the 6 carbons of the original glucose?

Glycolysis--------------------Pyruvate oxidation--------------------------------Krebs cycle
CCCCCC ----------------> CCC + CCC --------------------------> CC + CC + CO2 + CO2 -----------------> 4 CO2
glucose--------------------2 pyruvate-------------------------2 acetyl-CoA-----expelled---------------------expelled

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