Cellular respiration

SWAZZLE RULES!?! Cellular respiration is a process that describes the metabolic reactions and processes that take place in a cell to obtain chemical energy from fuel molecules. Energy is released by the oxidation of fuel molecules and is stored as "high-energy" carriers. The reactions involved in respiration are catabolic reactions in metabolism.

Fuel molecules commonly used by cells in respiration include glucose, amino acids and fatty acids, and a common oxidizing agent (electron acceptor) is molecular oxygen (O₂). There are organisms, however, that can respire using other organic molecules as electron acceptors instead of oxygen. Organisms that use oxygen as a final electron acceptor in respiration are described as aerobic, while those that do not are referred to as anaerobic.

The energy released in respiration is used to synthesize molecules that act as a chemical storage of this energy. One of the most widely used compounds in a cell is adenosine triphosphate (ATP) and its stored chemical energy can be used for many processes requiring energy, including biosynthesis, locomotion or transportation of molecules across cell membranes. Because of its ubiquitous nature, ATP is also known as the "universal energy currency", since the amount of it in a cell indicates how much energy is available for energy-consuming processes. This concept is taught in 10th grade Biology.

Aerobic respiration

Flowchart of cellular respiration

Aerobic respiration requires oxygen in order to generate energy(ATP). It is the preferred method of pyruvate breakdown from glycolysis and requires that pyruvate enter the mitochondrion to be fully oxidized by the Krebs cycle. The product of this process is energy in the form of ATP (Adenosine Triphosphate), by substrate-level phosphorylation, NADH and FADH2. The reducing potential of NADH and FADH2 is converted to more ATP via an electron transport chain with oxygen as the "terminal electron acceptor". Most of the ATP produced by cellular respiration is by oxidative phosphorylation, ATP molecules are made due to the chemiosmotic potential driving ATP synthase. Respiration is the process by which cells obtain energy when oxygen is present in the cell.

Theoretically, 36 ATP molecules can be made per glucose during cellular respiration, however, such conditions are generally not realized due to such losses as the cost of moving pyruvate into mitochondria. Aerobic metabolism is more efficient than anaerobic metabolism (which yields 2 mol ATP per 1 mol glucose). 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

Glycolysis is a metabolic pathway that is found in the cytoplasm of cells in all living organisms and does not require oxygen. The process converts one molecule of glucose into two molecules of pyruvate, and makes energy in the form of two net molecules of [[Adenosine triphosphate|ATP]]. Four molecules of ATP per glucose are actually produced but two are consumed for the preparatory phase. The initial phosphorylation of glucose is required to destabilize the molecule for cleavage into two triose sugars. During the pay-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 triose sugars are oxidized. Glycolysis takes place in the cytoplasm of the cell. The overall reaction can be expressed this way:

Glucose + 2 ATP + 2 NAD⁺ + 2 P_i + 4 ADP → 2 pyruvate + 2 ADP + 2 NADH + 4 ATP + 2 H₂O + 4 H⁺

Oxidative decarboxylation of pyruvate

Produces acetyl-CoA from pyruvate inside the mitochondrial matrix. This oxidation reaction also releases carbon dioxide as a product. In the process one molecule of NADH is formed per pyruvate oxidized.

Krebs cycle/Citric Acid cycle

When oxygen is present, acetyl-CoA enters the citric acid cycle inside the mitochondrial matrix, and gets oxidized to CO2 while at the same time reducing NAD to NADH. NADH can be used by the electron transport chain to create further ATP as part of oxidative phosphorylation. To fully oxidize the equivalent of one glucose molecule two acetyl-CoA must be metabolized by the Krebs cycle. Two waste products, H₂O and CO₂ are created during this cycle.

Oxidative phosphorylation

In eukaryotes, oxidative phosphorylation occurs in the mitochondrial cristae. It comprises the electron transport chain that establishes a proton gradient (chemiosmotic potential) across the inner membrane by oxidizing the NADH produced from the Krebs cycle. ATP is synthesised by the ATP synthase enzyme when the chemiosmotic gradient is used to drive the phosphorylation of ADP.

Theoretical yields

The yields in the table below are for one glucose molecule being fully oxidized into carbon dioxide. It is assumed that all the reduced coenzymes are oxidized by the electron transport chain and used for oxidative phosphorylation.

Step	coenzyme yield	ATP yield	Source of ATP
Glycolysis preparatory phase		-2	Phosphorylation of glucose and fructose 6-phosphate uses two ATP from the cytoplasm.
Glycolysis pay-off phase		4	Substrate-level phosphorylation
Glycolysis pay-off phase	2 NADH	4	Oxidative phosphorylation. Only 2 ATP per NADH since the coenzyme must feed into the electron transport chain from the cytoplasm rather than the mitochondrial matrix.
Oxidative decarboxylation	2 NADH	6	Oxidative phosphorylation
Krebs cycle		2	Substrate-level phosphorylation
	6 NADH	18	Oxidative phosphorylation
	2 FADH₂	4	Oxidative phosphorylation
Total yield		36 ATP	From the complete oxidation of one glucose molecule to carbon dioxide and oxidation of all the reduced coenzymes.

Although there is a theoretical yield of 36 ATP molecules per glucose during cellular respiration, such conditions are generally not realized due to losses such as the cost of moving pyruvate (from glycolysis), phosphate and ADP (substrates for ATP syhthesis) into the mitochondria. All are actively transported using carriers that utilise the stored energy in the proton electrochemical gradient.

The pyruvate carrier is a symporter and the driving force for moving pyruvate into the mitochondria is the movement of protons from the intermembrane space to the matrix.
The phosphate carrier is an antiporter and the driving force for moving phosphate ions into the mitochondria is the movement of hydroxyls ions from the matrix to the intermembrane space.
The adenine nucleotide carrier is an antiporter and exchanges ADP and ATP across the inner membrane. The driving force is due to the ATP (-4) having a more negative charge than the ADP (-3) and thus it dissipates some of the electrical component of the proton electrochemical gradient.

The outcome of these transport processes using the proton electrochemical gradient is that more than 3 H⁺ are needed to make 1 ATP. Obviously this reduces the theoretical efficiency of the whole process. Other factors may also dissipate the proton gradient creating an apparently leaky mitochondria. An uncoupling protein known as thermogenin is expressed in some cell types and is a channel that can transport protons. When this protein is active in the inner membrane it short circuits the coupling between the electron transport chain and ATP synthesis. The potential energy from the proton gradient is not used to make ATP but generates heat. This is particularly important in a baby's brown fat, for thermogenesis, and hibernating animals.

Anaerobic respiration

Main article: Anaerobic Respiration

In the absence of oxygen, pyruvate is not metabolized by cellular respiration but undergoes a process of fermentation. The pyruvate is not transported into the mitochondrion, but remains in the cytoplasm, where it is converted to waste products that may be removed from the cell. This serves the purpose of oxidizing the hydrogen carriers so that they can perform glycolysis again and removing the excess pyruvate. This waste product varies depending on the organism. In skeletal muscles, the waste product is lactic acid. This type of fermentation is called lactic acid fermentation. In yeast, the waste products are ethanol and carbon dioxide. This type of fermentation is known as alcoholic or ethanol fermentation.

Anaerobic respiration is less efficient at using the energy from glucose since 2 ATP are produced during anaerobic respiration per glucose, compared to the 36 ATP per glucose produced by aerobic respiration. This is because the waste products of anaerobic respiration still contain plenty of energy. Ethanol, for example, can be used in gasoline solutions. Glycolytic ATP, however, is created more quickly. Thus, during short bursts of strenuous activity, muscle cells use anaerobic respiration to supplement the ATP production from the slower aerobic respiration, so anaerobic respiration may be used by a cell even before the oxygen levels are depleted, as is the case in sports that do not require athletes to pace themselves, such as sprinting.

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