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Old Tuesday, June 09, 2009
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Default Cell Biology Mitochondria Part II



Steps from glycolysis to the electron transport chain

Once inside the cell, glucose is broken down to make ATP in two pathways. The first pathway requires no oxygen and is called anaerobic metabolism. This pathway is called glycolysis and it occurs in the cytoplasm outside the mitochondria. During glycolysis, glucose is broken down into pyruvate. Other foods like fats can also be broken down for use as fuel. Each reaction is designed to produce some hydrogen ions (electrons) that can be used to make energy packets (ATP). However, only 4 ATP molecules can be made by one molecule of glucose run through this pathway. That is why mitochondria and oxygen are so important. We need to continue the breakdown process with the Krebs’s cycle inside the mitochondria in order to get enough ATP to run all the cell functions.







How does the Krebs’s cycle work?

The whole idea behind respiration in the mitochondria is to use the Kreb’s cycle (also called the citric acid cycle) to get as many electrons out of the food we eat as possible. These electrons (in the form of hydrogen ions) are then used to drive pumps that produce ATP. The energy carried by ATP is then used for all kinds of cellular functions like movement, transport, entry and exit of products, division, etc.
To run the Kreb's cycle, you need several important molecules in addition to all the enzymes. First; you need pyruvate, which is made by glycolysis from glucose. Next, you need some carrier molecules for the electrons.
There are two types of these:
  • · One is called nicotinamide adenine dinucleotide (NAD+)
  • · The other is called flavin adenine dinucleotide (FAD+). The third molecule, of course, is oxygen.
Pyruvate is a 3-carbon molecule. After it enters the mitochondria, it is broken down to a 2-carbon molecule by a special enzyme. This releases carbon dioxide. The 2-carbon molecule is called Acetyl CoA and it enters the Kreb’s cycle by joining to a 4-carbon molecule called oxaloacetate. Once the two molecules are joined, they make a 6-carbon molecule called citric acid (2 carbons + 4 carbons = 6 carbons). That is where the Citric acid cycle got its name.... from that first reaction that makes citric acid. Citric acid is then broken down and modified in a stepwise fashion and, as this happens, hydrogen ions and carbon molecules are released. The carbon molecules are used to make more carbon dioxide and the hydrogen ions are picked up by NAD and FAD. Eventually, the process produces the 4-carbon oxaloacetate again. The reason the process is called a cycle, is because it ends up always where it started with oxaloacetate available to combine with more acetyl-coA.

Oxidative phosphorylation

First, some basic definitions. When you take hydrogen ions or electrons away from a molecule, you “oxidize” that molecule. When you give hydrogen ions or electrons to a molecule, you “reduce” that molecule. When you give phosphate molecules to a molecule, you “phosphorylate” that molecule. So, oxidative phosphorylation (very simply) means the process that couples the removal of hydrogen ions from one molecule and giving phosphate molecules to another molecule. As the Kreb’s cycle runs, hydrogen ions (or electrons) are donated to the two carrier molecules in 4 of the steps. Either NAD or FAD picks them up and these carrier molecules become NADH and FADH (because they now are carrying a hydrogen ion).
These electrons are carried chemically to the respiratory or electron transport chain found in the mitochondrial cristae . The NADH and FADH essentially serve as a ferry in the lateral plane of the membrane diffusing from one complex to the next. At each site is a hydrogen (or proton) pumps, which transfers hydrogen from one side of the membrane to the other. This creates a gradient across the inner membrane with a higher concentration of Hydrogen ions in the intercristae space (this is the space between the inner and outer membranes).
The electrons are carried from complex to complex by ubiquinone and cycochrome C.
The third pump in the series catalyzes the transfer of the electrons to oxygen to make water. This chemiosmotic pumping creates an electrochemical proton gradient across the membrane, which is used to drive the “energy-producing machine”the ATP synthase. This molecule is found in small elementary particles that project from the cristae.
As stated above, this process requires oxygen, which is why it is called "aerobic metabolism". The ATP synthase uses the energy of the hydrogen ion (also called proton) gradient to form ATP from ADP and Phosphate. It also produces water from the hydrogen and the oxygen. Thus, each compartment in the mitochondrion is specialized for one phase of these reactions.

This is how oxidation is coupled to phosphorylation:

NAD and FAD remove the electrons that are donated during some of the steps of the Kreb's or Citric acid cycle. Then, they carry the electrons to the electron transport pumps and donate them to the pumps. So, NAD and FAD are “oxidized” because they lose the hydrogen ions to the pumps. The pumps then transport the hydrogens ions to the space between the two membranes where they accumulate in a high enough concentration to fuel the ATP pumps. With sufficient fuel, they “phosphorylate” the ADP. That is how “oxidation” is coupled to “phosphorylation”.
The hydrogens that get pumped back into the matrix by the ATP pump then combine with the oxygen to make water. And that is very important because, without oxygen, they will accumulate and the concentration gradient needed to run the ATP pumps will not allow the pumps to work.


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