Cell Respiration

1. How do cells obtain energy for their functioning?

Cells obtain energy for their metabolic reactions from the breaking of organic molecules with high energetic content. This energy is mostly stored as ATP molecules.

The process of obtaining energy in order to produce ATP molecules is named cellular respiration.

ATP, or adenosine triphosphate, is formed after the binding of one phosphate (phosphorylation) to one ADP (adenosine diphosphate) molecule. This is a process that stores energy into the produced ATP molecule.

When ATP gives energy to the cellular metabolism it loses one of its phosphates and ADP reappears.

ADP can also lose more phosphates and generate AMP (adenosine monophosphate) or even non-phosphorylated adenosine. Adenosine production from ATP is a solution used in tissues that need urgent oxygen supply, for example, in the heart during myocardial infarction (heart attack), since adenosine has a local vasodilator effect thus providing faster vasodilation than other physiological methods.

Cell Respiration Review - Image Diversity: ATP phosphorylation

There are two types of cell respiration: aerobic cell respiration, a reaction with participation of molecular oxygen (O2), and anaerobic cell respiration, without participation of molecular oxygen but with other inorganic molecules as oxidant. There are several varieties of anaerobic cell respiration, the main one is fermentation.

Some cells that usually obtain energy from aerobic cellular respiration can carry out fermentation when oxygen is not available.

There are bacteria and fungi that under absence of oxygen use their anaerobic metabolic capability for energetic supply. Muscle cells carry out fermentation too when oxygen is scarce.

Aerobic organisms are those whose cells do not survive without oxygen since they depend on aerobic cell respiration to obtain energy for ATP production. Anaerobic organisms are those that live or can live under oxygen-lacking environments.

Facultative anaerobic beings, like the fungi Saccharomyces cerevisiae, a brewing yeast, can survive under oxygen-poor environments carrying out fermentation. However when oxygen is available these beings carry out aerobic respiration.

Obligate anaerobic beings are those that cannot survive when oxygen is present. Some fungi, some bacteria (like the agent of botulism Clostridium botulinum, and the agent of tetanus, Clostridium tetani) and some protozoans are examples of obligate anaerobes.

The two main types of fermentation are alcoholic fermentation and lactic fermentation.

In alcoholic fermentation pyruvic acid, an intermediate molecule, is converted into ethanol with liberation of carbon dioxide. The alcoholic fermentation equation is as follows:

C6H12O6 + 2 ADP + P --> 2 C2H5OH + 2 CO2 + 2 ATP

In lactic fermentation pyruvic acid is transformed into lactic acid and there is no production of carbon dioxide. The lactic fermentation equation is:

C6H12O6 + 2 ADP + P --> 2 C3H5OOH + 2 ATP

In fermentation glucose (sugar) is degraded into pyruvic acid (each glucose molecule forms two pyruvic acid molecules). In this process two molecules of ATP are produced.

According to the type of fermentation, pyruvic acid can produce ethanol and carbon dioxide (in alcoholic fermentation) or lactic acid (in lactic fermentation). There are other varieties of fermentation in which pyruvic acid can generate acetic acid (acetic fermentation), propionic acid, isopropanol (an alcohol too), etc. The type of fermentation depends on the species of the involved organisms.

Fermentation has the function of making cakes and breads grow. This is accomplished by liberation of carbon dioxide in alcoholic fermentation as the gas passes through the dough and makes it grow. In lactic fermentation there is no liberation of carbon dioxide and the desired result would not be obtained.

Some bacteria ferment milk lactose by lactic fermentation producing lactic acid. This product is responsible for the acidic flavor of yogurts, curd and milk.

A typical fermentation process due to oxygen scarcity happens in the muscle tissue. Under intense use muscles demand too much energy (ATP) and consume much more oxygen to produce that energy. High consumption leads to oxygen scarcity and the muscle cells begin to make lactic fermentation trying to satisfy their energetic needs. In this situation muscle pain, cramps and fatigue are due to the lactic acid released by fermentation.

In fermentation from one glucose molecule two ATP molecules are produced. In aerobic respiration, a much more productive process, from one glucose molecule 36 ATP molecules are made.

The cell organelles that are specialized in aerobic respiration are the mitochondria.

Cell Respiration Review - Image Diversity: mitocondria

Mitochondria are organelles delimited by two lipid membranes. The inner membrane invaginates to the interior of the organelle forming cristae and delimiting an internal space known as the mitochondrial matrix.

Cell Respiration Review - Image Diversity: mitochondria structure

The three phases of aerobic cell respiration are glycolysis, Krebs cycle and respiratory chain (also known as the electron transport chain).

Glycolysis, the first stage of the aerobic cell respiration, is a process in which glucose is degraded (broken) to form two pyruvic acid molecules along with the formation of two ATP and two NADH.

Glycolysis is a complex reaction implying the formation of several intermediate molecules until pyruvic acid molecules are made. Although two ATP molecules are consumed in the reaction, there is also production of four molecules of ATP, thus a positive balance of two ATP molecules is obtained. Two NADH molecules are also produced. In glycolysis the 6-carbon structure of glucose is broken and two organic chains of three carbons each are made; these chains give birth to two pyruvic acid molecules.

Cell Respiration Review - Image Diversity: glycolysis

Glycolysis happens in the cytosol and not within the mitochondria. Pyruvic acid molecules later enter mitochondria to participate in the next phase of the aerobic cell respiration.

Glycolysis is a process similar to glucose degradation in fermentation. It produces (final balance) two molecules of ATP for each broken glucose.

NAD (nicotinamide adenine dinucleotide) is a hydrogen acceptor necessary as reductant (to receive hydrogen) in some reactions in which it is reduced and converted into NADH2. During glycolysis two NAD molecules retrieve hydrogens liberated after an intermediate reaction thus forming NADH2.

The pyruvic acid molecules made in cytosol by glycolysis enter into the mitochondria.

Within the mitochondria each pyruvic acid molecule is converted into one molecule of acetyl-CoA (acetyl coenzyme A) with liberation of one carbon dioxide. The Krebs cycle (also known as citric acid cycle), the second stage of aerobic respiration, then begins.

Pyruvic acid is 2-oxopropanoic acid. It is thus a molecule made of three linearly bound carbons with one extremity forming the organic acid function (COOH) and the middle carbon binding to an oxygen atom by double bond.

Each glucose molecule “cycles” the Krebs cycle twice because after glycolysis each used glucose has generated two pyruvic acid molecules and each pyruvic acid is converted in a 1:1 proportion into acetyl CoA. Each acetyl CoA then cycles the Krebs cycle once.

Cell Respiration Review - Image Diversity: Krebs cycle

The Krebs cycle is called the final common pathway of the degradation of organic compounds because it is also possible to generate acetyl CoA from the degradation of lipids and proteins. Since acetyl CoA is the substrate that triggers the Krebs cycle, this process is called the final common pathway for being activated by other organic molecules (lipids and proteins) and not only by glucose.

The organism uses energetic reserves of fat and proteins to cycle the Krebs cycle when undergoing malnutrition or when there is no glucose available for the cells.

After each round of the Krebs cycle two carbon dioxide molecules, eight protons (hydrogen ions) captured by NAD and FAD (a hydrogen acceptor too) and one ATP molecule are produced.

During the Krebs cycle acetyl CoA is degraded. At the end the utile energy is incorporated into hydrogens transported by FADH2 and NADH2 molecules.

Each round of the Krebs cycle liberates two carbon dioxide molecules.

At the end of the cycle all carbon atoms from the original glucose molecule degraded in glycolysis are already liberated incorporated into carbon dioxide molecules. That occurs because for each glucose two pyruvic acid molecules were made by glycolysis. Each of these two pyruvic acids then is converted into acetyl CoA with liberation of one carbon dioxide molecule (two in total). Since each of the two produced acetyl CoA cycles the Krebs cycle once, from the initial glucose two rounds of the Krebs cycle is generated and so four other carbon dioxide molecules are made.

All of the six carbons of the glucose molecule are then incorporated into six carbon dioxide molecules (two made during acetyl CoA formation and four during the two cycles of the Krebs cycle).

Respiratory chain, or the electron transport chain, is performed by protein systems located in the inner membrane of the mitochondria. Energized electrons of hydrogen atoms transported by NADH2 and FADH2 are the products of the preceding phases used in the respiratory chain.

Cell Respiration Review - Image Diversity: respiratory chain

Cytochromes are proteins of the internal mitochondrial membrane that are specialized in electron transfer and participate in the respiratory chain. Energized electrons liberated by the hydrogen donors NADH2 and FADH2 (then reconverted into NAD and FAD) pass through a sequence of cytochromes losing energy in each passage. The energy is then used in the synthesis of ATP.

FADH2 and NADH2 oxidate into FAD and NAD and liberate hydrogen ions and highly energized electrons in the beginning of the respiratory chain.

The energy lost by electrons that pass through the cytochromes is used to pump protons (hydrogen ions) out of the inner mitochondrial membrane (to the region between the inner and the outer membranes of the mitochondrion). Hydrogen concentration gradient between the inner and the outer spaces delimited by the inner membrane forces protons (hydrogen ions) to return to the mitochondrial matrix (the region inside the inner membrane) however that return is only possible if hydrogen ions pass through an enzymatic complex called ATP synthetase embedded in the inner membrane. In that passage the ATP synthetase phosphorylates ADP and then ATP molecules are produced.

Hydrogen liberated in the mitochondrion then combines with oxygen to form water. As a reaction that depends on oxygen this type of ATP synthesis is called oxidative phosphorylation.

Oxygen enters the aerobic respiration in its final phase, the respiratory chain. It is of fundamental importance because it is responsible for the maintenance of the hydrogen concentration gradient between the spaces separated by the inner mitochondrial membrane. This gradient promotes the functioning of the ATP synthetase and thus the phosphorylation of ADP to form ATP. In the space inside the inner membrane oxygen binds to free hydrogens to form water and this hydrogen consumption keeps the hydrogen gradient and the proton traffic through the ATP synthetase.

The entire aerobic respiration process has the intent to make the ATP synthetase work. Aerobic beings, for example, we humans, need to breathe oxygen to maintain that hydrogen concentration gradient and keep the ATP synthetase working.

Cell Respiration Review - Image Diversity: ATP synthetase

Cyanide is a poison that inhibits the last cytochrome of the respiratory chain, interrupting the ATP formation and thus leading the cell to death.

Anoxia is a situation in which there is no available oxygen in the cell. Whitout oxygen the respiratory chain stops, there is no ATP production, the cell does not obtain energy and dies.

Anoxia can be caused, for example, by pulmonary insufficiency (drowning, extensive pulmonary injuries, etc.), by obstructions, halts and deficiencies in tissue circulation (atherosclerosis of the coronary arteries that irrigate the myocardium, tourniquets, heart arrest), by hemolysis (lysis of red blood cell) or hemoglobin diseases (anemias, fetal erythroblastosis), etc.

After aerobic respiration 38 ATP molecules are made with the consumption of one glucose molecule (but two of these ATP are consumed by glycolysis). The net gain of the process is then 36 ATP molecules per glucose molecule.

The general equation of the aerobic respiration is:

C6H12O6 + 6 O2 + 36 ADP + 36 P --> 6 CO2 + 6 H2O + 36 ATP

Molecular oxygen (O2) consumption has direct relation to the cell metabolic rate in aerobic cells and so to the metabolic rate of the organisms. Cells having higher metabolic activity demand more energy and such energy comes from ATP molecules. As there is need for ATP production, the intensity of aerobic cell respiration is also higher and then more oxygen is consumed.

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