Cellular respiration

Cellular respiration describes the metabolic reactions and processes that take place in a cell or across the cell membrane to get biochemical energy from fuel molecules and then release of the cells' waste products. Energy can be released by the oxidation of multiple fuel molecules and is stored as "high-energy" carriers. The reactions involved in respiration are catabolic reactions in metabolism. The movement of a pair of electrons down the electron transport chain produces enough energy to form 32 to 34 ATP molecules from ADP.

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.

Aerobic 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.

Simplified reaction: C₆H₁₂O_{6 (aq)} + 6O_{2 (g)} → 6CO_{2 (g)} + 6H₂O _(l) ΔH_c -2880 kJ

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. Biology textbooks often state that between 36-38 ATP molecules can be made per oxidised glucose molecule during cellular respiration (2 from glycolysis, 2 from the Krebs cycle, and about 32-34 from the electron transport system). Generally, 38 ATP molecules are formed from aerobic respiration. 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 mitochondrial matrix.

Aerobic metabolism is 19 times 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

Main article: 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 ATP. Four molecules of ATP per glucose are actually produced; however, 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. The overall reaction can be expressed this way:

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

Oxidative decarboxylation of pyruvate

Main article: Pyruvate decarboxylation

The pyruvate is oxidized to acetyl-CoA and CO₂ by the Pyruvate dehydrogenase complex, a cluster of enzymes—multiple copies of each of three enzymes—located in the mitochondria of eukaryotic cells and in the cytosol of prokaryotes. In the process one molecule of NADH is formed per pyruvate oxidized.

Citric Acid cycle

Main article: Citric acid cycle

This is also called the Krebs cycle or the tricarboxylic acid cycle. When oxygen is present, acetyl-CoA is produced from pyruvate. If oxygen is not present the cell undergoes fermentation of the pyruvate molecule. If acetyl-CoA is produced the molecule then enters the citric acid cycle (Krebs 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

Main articles: Oxidative phosphorylation, Electron transport chain, Electrochemical gradient, and ATP synthase

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
	2 NADH	4 (6)	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. If the malate shuttle is used to move NADH into the mitochondria this might count as 3Small TextSmall TextSmall TextSmall TextSmall TextSmall Text ATP per NADH.
Oxidative decarboxylation of pyruvate	2 NADH	6	Oxidative phosphorylation
Krebs cycle		2	Substrate-level phosphorylation
	6 NADH	18	Oxidative phosphorylation
	2 FADH2	4	Oxidative phosphorylation
Total yield		36 (38) 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 36-38 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 synthesis) 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 and the likely maximum is closer to 28-30 ATP molecules. In practice the efficiency may be even lower due to the inner membrane of the mitochondria being slightly leaky to protons. 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

Without 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. The ATP generated in this process is made by substrate phosphorylation, which is phosphorylation that does not involve oxygen.

Anaerobic respiration is less efficient at using the energy from glucose since 2 ATP are produced during anaerobic respiration per glucose, compared to the 30 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 (petrol) solutions. Glycolytic ATP, however, is created more quickly. For prokaryotes to continue a rapid growth rate when they are shifted from an aerobic environment to an anaerobic environment, they must increase the rate of the glycolytic reactions. 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.

Efficiency of aerobic and anaerobic respiration

Aerobic respiration During aerobic respiration 38 molecules of ATP are produced for every molecule of glucose that is oxidised. C₆H₁₂O_{6 (aq)} + 6O_{2 (g)} → 6CO_{2 (g)} + 6H₂O _(l) + 38 ATP The energy released by the complete oxidation of glucose is 2880KJ per mole. The energy contained in 1 mole of ATP is 30.6KJ. Therefore the energy contained in 38 moles of ATP is 30.6×38=1162.8 kJ. Therefore efficiency of transfer of energy in aerobic respiration is=1162.8/2880=40.4%.

Anaerobic respiration (1) Yeast (alcoholic fermentation). During alcoholic fermentation, two molecules of ATP are produced. for every molecule of glucose used.

glucose → 2ethanol + 2CO2 (g) +2 ATP

The total energy released by the conversion of glucose to ethanol is 210kj per mole. The energy contained in 2 molecules of ATP is 2×30.6=61.2kJ.Therefore efficiency of transfer of energy during alcoholic fermentation is 61.2/210=29.1%.

(2) Muscle (lactate fermentation). During lactate fermentation, 2 molecules of ATP are produced for every molecule of glucose used.

glucose → 2 lactate + 2ATP

The total energy released by conversion of glucose to lactate is 150kj per mole. Therefore efficiency of transfer of energy in lactic acid fermentation is 61.2/150=40.8%. The amount of energy captured as ATP during aerobic respiration is 19 times as much as for anaerobic respiration.From this point of view Aerobic respiration is more efficient than anaerobic respiration.This is because a great deal of energy remains locked within lactate and ethanol.

Extract from 'Biological Science' by D.J. Taylor, N.P.O Green and G.W. Stout, Cambridge University Press, ISBN 0 521 639239

See also

• Tetrazolium chloride: cellular respiration indicator

External links

• Chart of Important Metabolic Products
• A detailed description of respiration vs. fermentation
• Kimball's online resource to cellular respiration
• Cellular Respiration and Fermentation at Clermont College