Cellular Respiration

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Cellular Respiration
The term cellular respiration refers to the biochemical pathway by which cells release energy from the chemical bonds of food molecules and provide that energy for the essential processes of life. All living cells must carry out cellular respiration. It can be aerobic respiration in the presence of oxygen or anaerobic respiration. Prokaryotic cells carry out cellular respiration within the cytoplasm or on the inner surfaces of the cells. More emphasis here will be placed on eukaryotic cells where the mitochondria are the site of most of the reactions. The energy currency of these cells is ATP, and one way to view the outcome of cellular respiration is as a production process for ATP.

The graphic below can serve as a reminder of some of the processes involved in cellular respiration. Cellular respiration produces CO2 as a metabolic waste. This CO2 binds with water to form carbonic acid, helping to maintain the blood's pH. Since too much CO2would lower the blood's pH too much, the removal of the excess CO2 must be accomplished on an ongoing basis.

Aerobic Respiration
Aerobic respiration, or cell respiration in the presence of oxygen, uses the end product of glycolysis (pyruvate) in the TCA cycle to produce much more energy currency in the form of ATP than can be obtained from any anaerobic pathway. Aerobic respiration is characteristic of eukaryotic cells when they have sufficient oxygen and most of it takes place in the mitochondria.

Anaerobic Respiration
The first step in cellular respiration in all living cells is glycolysis, which can take place without the presence of molecular oxygen. If oxygen is present in the cell, then the cell can subsequently take advantage of aerobic respiration via the TCA cycle to produce much more usable energy in the form of ATP than any anaerobic pathway. Nevertheless, the anaerobic pathways are important and are the sole source of ATP for many anaerobic bacteria. Eukaryotic cells also resort to anaerobic pathways if their oxygen supply is low. For example, when muscle cells are working very hard and exhaust their oxygen supply, they utilize the anaerobic pathway to lactic acid to continue to provide ATP for cell function. Glycolysis itself yields two ATP molecules, so it is the first step of anaerobic respiration. Pyruvate, the product of glycolysis, can be used in fermentation to produce ethanol and NAD+ or for the production of lactate and NAD+. The production of NAD+ is crucial because glycolysis requires it and would cease when its supply was exhausted, resulting in cell death. A general sketch of the anaerobic steps is shown below. It follows Karp's organization.

Anaerobic respiration (both glycolysis and fermentation) takes place in the fluid portion of the cytoplasm whereas the bulk of the energy yield of aerobic respiration takes place in the mitochondria. Anaerobic respiration leaves a lot of energy in the ethanol or lactate molecules that the cell cannot use and must excrete.

Glucose
Glucose is a carbohydrate, and is the most important simple sugar in human metabolism. Glucose is called a simple sugar or a monosaccharide because it is one of the smallest units which has the characteristics of this class of carbohydrates. Glucose is also sometimes called dextrose. Corn syrup is primarily glucose. Glucose is one of the primary molecules which serve as energy sources for plants and animals. It is found in the sap of plants, and is found in the human bloodstream where it is referred to as "blood sugar". The normal concentration of glucose in the blood is about 0.1%, but it becomes much higher in persons suffering from diabetes.

Glycolysis
Glycolysis, part of cellular respiration, is a series of reactions that constitute the first phase of most carbohydrate catabolism, catabolism meaning the breaking down of larger molecules into smaller ones. The word glycolysis is derived from two Greek words and means the breakdown of something sweet. Glycolysis breaks down glucose and forms pyruvate with the production of two molecules of ATP. The pyruvate end product of glycolysis can be used in either anaerobic respiration if no oxygen is available or in aerobic respiration via the TCA cycle which yields much more usable energy for the cell.

Electron Transport in the Energy Cycle of the Cell

The eukaryotic cell's most efficient path for production of vital ATP is the aerobic respiration that takes place in themitochondria. After glycolysis, thepyruvate product is taken into the mitochondia and is further oxidized in theTCA cycle. This cycle deposits energy in the reduced coenzymes which transfer that energy through what is called the electron transport chain.

The TCA Cycle
The tricarboxylic acid cycle (TCA cycle) is a series of enzyme-catalyzed chemical reactions that form a key part of aerobic respiration in cells. This cycle is also called the Krebs cycle and the citric acid cycle. The greatly simplified cycle below starts with pyruvate, which is the end product of gylcolysis, the first step of all types of cell respiration.

Adenosine Triphosphate
Adenosine triphosphate (ATP) is considered by biologists to be the energy currency of life. It is the high-energy molecule that stores the energy we need to do just about everything we do. It is present in the cytoplasm and nucleoplasm of every cell, and essentially all the physiological mechanisms that require energy for operation obtain it directly from the stored ATP. (Guyton) As food in the cells is gradually oxidized, the released energy is used to re-form the ATP so that the cell always maintains a supply of this essential molecule. Karp quotes an estimate that more than 2 x 10 26 molecules or >160kg of ATP is formed in the human body daily! ATP is remarkable for its ability to enter into many coupled reactions, both those to food to extract energy and with the reactions in other physiological processes to provide energy to them. In animal systems, the ATP is synthesized in the tiny energy factories called mitochondria.

We all need energy to function and we get this energy from the foods we eat. The most efficient way for cells to harvest energy stored in food is through cellular respiration, a catabolic pathway for the production of adenosine triphosphate (ATP). ATP, a high energy molecule, is expended by working cells. Cellular respiration occurs in both eukaryotic and prokaryotic cells. It has three main stages: glycolysis, the citric acid cycle, and electron transport.

Cellular Respiration Glycolysis: Glycolysis literally means "splitting sugars." Glucose, a six carbon sugar, is split into two molecules of a three carbon sugar. In the process, two molecules of ATP, two molecules of pyruvic acid and two "high energy" electron carrying molecules of NADH are produced. Glycolysis can occur with or without oxygen. In the presence of oxygen, glycolysis is the first stage of cellular respiration. Without oxygen, glycolysis allows cells to make small amounts of ATP. This process is called fermentation. The Citric Acid Cycle: The Citric Acid Cycle or Krebs Cycle begins after the two molecules of the three carbon sugar produced in glycolysis are converted to a slightly different compound (acetyl CoA). Through a series of intermediate steps, several compounds capable of storing "high energy" electrons are produced along with two ATP molecules. These compounds, known as nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD), are reduced in the process. These reduced forms carry the "high energy" electrons to the next stage. The Citric Acid Cycle occurs only when oxygen is present but it doesn't use oxygen directly. Electron Transport: Electron Transport requires oxygen directly. The electron transport "chain" is a series of electron carriers in the membrane of the mitochondria in eukaryotic cells. Through a series of reactions, the "high energy" electrons are passed to oxygen. In the process, a gradient is formed, and ultimately ATP is produced. Maximum ATP Yields: In summary, prokaryotic cells can yield a maximum of 38 ATP molecules while eukaryotic cells can yield a maximum of 36. In eukaryotic cells, the NADH molecules produced in glycolysis pass through the mitochondrial membrane, which "costs" two ATP molecules.

Aerobic vs. Anaerobic Respiration
All living things need a continuous supply of energy to keep their cells functioning normally and to stay healthy. Some organisms, called autotrophs, can produce their own energy using sunlight through the process of photosynthesis. Others, like humans, need to eat food in order to produce energy. However, that is not the type of energy cells use to function. Instead they use a molecule called Adenosine triphosphate (ATP) to keep themselves going. The cells, therefore, must have a way to

take the chemical energy stored in food and transform it into the ATP they need to function. The process cells undergo to make this change is called cellular respiration. Two Types of Cellular Respiration Cellular respiration can be aerobic (meaning "with oxygen") or anaerobic ("without oxygen"). Which route the cells take to create the ATP depends solely on whether or not there is enough oxygen present to undergo aerobic respiration. If there is not enough oxygen present for aerobic respiration, then the organism will resort to using anaerobic respiration. Aerobic Respiration In order to maximize the amount of ATP made in the process of cellular respiration, oxygen must be present. As eukaryotic species evolved over time, they became more complex with more organs and body parts. It became necessary for cells to be able to create as much ATP as possible to keep these new adaptations running properly. Early Earth's atmosphere had very little oxygen. It wasn't until after autotrophs became abundant and released large amounts of oxygen as a byproduct of photosynthesis that aerobic respiration could evolve. The oxygen allowed each cell to produce many times more ATP than their ancient ancestors that relied on anaerobic respiration. This process happens in the cell organelle called the mitochondria. Anaerobic Respiration More primitive is the process of anaerobic respiration (also known as fermentation). Anaerobic respiration starts out the same way as aerobic respiration, but it stops part way through the pathway because the oxygen is not available for it to finish the aerobic respiration process. This type of cellular respiration makes many fewer ATP and also releases byproducts of either lactic acid or alcohol. Like aerobic respiration, anaerobic respiration happens in the mitochondria. Lactic acid fermentation is the type of anaerobic respiration humans undergo if there is a shortage of oxygen. For example, long distance runners experience a buildup of lactic acid in their muscles because they are not taking in enough oxygen to keep up with the demand of energy needed for the exercise. The lactic acid can even cause cramping and soreness in the muscles as time goes on. Alcoholic fermentation does not happen in humans. Yeast is a good example of an organism that undergoes alcoholic fermentation. The same process that goes on in the mitochondria during lactic acid fermentation also happens in alcoholic fermentation. The only difference is that the byproduct of alcoholic fermentation is ethyl alcohol. Alcoholic fermentation is important for the beer industry. Beer makers add yeast which will undergo alcoholic fermentation to add alcohol to the brew. Wine fermentation is also similar and provides the alcohol for the wine. Which is Better? Aerobic respiration is much more efficient at making ATP than anaerobic respiration. Without oxygen, the Krebs Cycle and the Electron Transport Chain in cellular respiration get backed up and will not work any

longer. This forces the cell to undergo the much less efficient anaerobic respiration. While aerobic respiration can produce up to 36 ATP, anaerobic respiration can only have a net gain of 2 ATP. Evolution and Respiration The most ancient type of respiration is anaerobic. Since there was little to no oxygen present when the first eukaryotic cells evolved through endosymbiosis, they could only undergo anaerobic respiration. This was not a problem, however, since those first cells were unicellular. Producing only 2 ATP at a time was enough to keep the single cell running. As multicellular eukaryotic organisms began to appear on Earth, the larger and more complex organisms needed to produce more energy. Through natural selection, organisms with more mitochondria that could undergo aerobic respiration survived and reproduced, passing on these favorable adaptations to their offspring. The more ancient versions could no longer keep up with the demand for ATP in the more complex organism and went extinct.

Aerobic respiration[edit]

Aerobic respiration (red arrows) is the main means by which both fungi and plants utilize energy in the form of organic compounds that were previously created through photosynthesis (green arrow).

Aerobic respiration requires oxygen in order to generate ATP. Although carbohydrates, fats, and proteins can all be processed and consumed as reactants, it is the preferred method of pyruvate breakdown in glycolysis and requires that pyruvate enter the mitochondrion in order to be fully oxidized by the Krebs cycle. The product of this process is carbon dioxide and water but the energy transferred is used to break strong bonds in ADP as the third phosphate group is added to form ATP (adenosine triphosphate), by substrate-level phosphorylation, NADH and FADH2 Simplified reaction: C6H12O6 (s) + 6 O2 (g) → 6 CO2 (g) + 6 H2O (l) + heat

ΔG = -2880 kJ per mole of C6H12O6 The negative ΔG indicates that the reaction can occur spontaneously. The reducing potential of NADH and FADH2 is converted to more ATP through an electron transport chain with oxygen as the "terminal electron acceptor". Most of the ATP produced by aerobic cellular respiration is made by oxidative phosphorylation. This works by the energy released in the consumption of pyruvate being used to create a chemiosmotic potential by pumping protons across a membrane. This potential is then used to drive ATP synthase and produce ATP from ADP and a phosphate group. Biology textbooks often state that 38 ATP molecules can be made per oxidised glucose molecule during cellular respiration (2 from glycolysis, 2 from the Krebs cycle, and about 34 from the electron transport [2] system). However, this maximum yield is never quite reached due to losses (leaky membranes) as well as the cost of moving pyruvate and ADP into the mitochondria's matrix and current estimates range [2] around 29 to 30 ATP per glucose. Aerobic metabolism is up to 15 times more efficient than anaerobic metabolism (which yields 2 molecules ATP per 1 molecule glucose). However some anaerobic organisms, such as Methanogen are able to continue with anaerobic respiration, yielding more ATP by using other inorganic molecules (not oxygen) as a final electron acceptors in the electron transport chain. They share the initial pathway of glycolysis but aerobic metabolism continues with the Krebs cycle and oxidative phosphorylation. The post glycolytic reactions take place in the mitochondria in eukaryotic cells, and in the cytoplasm in prokaryotic cells.

Glycolysis[edit]

Out of the cytoplasm it goes into the Krebs cycle where the acetyl CoA. It then mixes with CO2 and makes 2 ATP, NADH, and FADH. From there the NADH and FADH go into the NADH reductase, which produces the enzyme. The NADH pulls the enzyme's electrons to send through the electron transport chain. The electron transport chain pulls H+ ions through the chain. From the electron transport chain the released hydrogen ions make ADP for an end result of 32 ATP. 02 attracts itself to the left over electron to make water. Lastly, ATP leaves through the ATP channel and out of the mitochondria.

Main article: Glycolysis Glycolysis is a metabolic pathway that takes place in the cytosol of cells in all living organisms. This pathway can function with or without the presence of oxygen. Aerobic conditions produce pyruvate and

anaerobic conditions produce lactate. In aerobic conditions, the process converts one molecule of glucose into two molecules of pyruvate (pyruvic acid), generating energy in the form of two net molecules of ATP. Four molecules of ATP per glucose are actually produced; however, two are consumed as part of the preparatory phase. The initial phosphorylation of glucose is required to increase the reactivity (decrease its stability) in order for the molecule to be cleaved into two pyruvate molecules by the enzyme Aldolase. During thepay-off phase of glycolysis, four phosphate groups are transferred to ADP by substrate-level phosphorylation to make four ATP, and two NADH are produced when the pyruvate are oxidized. The overall reaction can be expressed this way: Glucose + 2 NAD + 2 Pi + 2 ADP → 2 pyruvate + 2 NADH + 2 ATP + 2 H + 2 H2O + heat Starting with glucose, 1 ATP is used to donate a phosphate to glucose to produce glucose 6phosphate. Glycogen can change into glucose 6-phosphate as well with the help of glycogen phosphorylase. During Energy metabolism, glucose 6-phosphate turns into fructose 6-phosphate. An additional ATP is used to phosphorylate fructose 6-phosphate into fructose 1,6-disphosphate by the help of phosphofructokinase. Fructose 1,6-diphosphate then splits into two phosphorylated molecules with three carbon chains that later degrades into pyruvate.
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