Cellular Metabolism: Ingestion, Digestion, Egestion, and Energy Production
Ingestion, digestion and egestion cell
Many nutrients enter cells in its interior, reducing (if applicable) monomers and, sometimes, eliminate waste. By analogy with the digestive processes of an organism, one can speak of ingestion, digestion and egestion phones.
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Ingestion
Ions and small molecules can cross the cell membrane by diffusion or active transport, but the high molecular mass particles must penetrate within the cell by endocytosis.
Some protozoa ingest large objects, such as bacteria, thanks to a variant of endocytosis:
Phagocytosis
But in vertebrates, only certain cells such as neutrophils and macrophages carry out this process to eliminate dying cells or infectious microorganisms, never for nutritional purposes.
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Digestion
In chemical terms, digest is hydrolyzed, ie break specific links by reaction with water. In eukaryotic cells this process occurs in lysosomes, through special proteins known as hydrolases.
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Egestion
Depending on the type of cell, the material could not be digested by hydrolases may be expelled by exocytosis or held indefinitely, in which case the cells are in state of “chronic constipation.”
Forms of energy production
Phototrophs agencies capture a small fraction of solar energy reaching the Earth and the “concentrated” in the form of complex molecules, the rest is reflected or re-emitted as infrared radiation, and dissipates in space. Scattered is the amount greater than the concentrated, so it is not broken the second law of thermodynamics. Examples chlorophyll parenchyma cells of plants and algae cells.
For their part, agencies chemotrophs extract energy stored in chemical bonds of molecules nutritious. Again dissipate a significant fraction of the energy received, and divert a small part for all kinds of cellular work, including the synthesis of complex macromolecules. Chemotrophs cells known as, among which include all animal cells and most protozoa, get free energy from chemical energy, ie, associated molecules, following the earlier analogy, are like partially compressed springs. Chemotrophs cells ingest these molecules and smaller molecules gradually degrade, thereby releasing the energy of these ‘springs compressed.
Ways to obtain electron
The flow of electrons in redox reactions is responsible, directly or indirectly, for all the work carried out by cells. In fact, in the catabolic pathways of electron donors often act as sources of energy. In nature there are many electron donors and agencies according to their nature may be:
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Lithotrophic
Are those agencies that extract electrons from inorganic molecules. For example, plants oxidize water, producing O 2 as a byproduct.
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Organotrophic
They are organisms that, like animals, oxidize organic materials, the electrons in addition to obtaining chemical energy.
Keep in mind that what really free energy is the electron donor for himself, but the chemical reaction which oxidizes. If the giver has a lower affinity for the electron acceptor, these electrons will flow spontaneously from first to second, and release energy in the process. Cells have several mechanisms to harness this energy and make biological work.
Metabolism
The utilization by the sum of all the chemical transformations that occur in cells.
Metabolism is a highly coordinated cellular activity, consisting of series of chemical reactions called metabolic pathways.
A metabolic pathway consists of between 2 and 20 consecutive reactions, organized in such a way that the product of the first reaction becomes the reactant of the second, and so on.
At each stage of the pathway there is a small chemical change, usually the addition, transfer or disposal of an atom or functional group.
The overall result is the conversion of a precursor molecule called the final product through a series of metabolic intermediates or metabolites.
Some metabolic pathways are linear, others are branched (for example, several products are formed from a precursor) and others are cyclical (one component of the path is regenerated during the transformation of precursor into product).
The overall equation of a metabolic pathway is obtained by adding member to member chemical equations that form (ie, writing down all the reactants on the left and all the products on the right), and eliminating the metabolites that appear in equal amounts on both sides of the equation. So the cyclical path of the right figure the equations are:
1.A + X 1 -> B
2.B -> C + Y
3.C + X 2 -> D
4.D -> 2A
The overall equation is X1 + X2 -> Y + A
You can sort the pathways into two categories:
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Catabolism
It is the degradation phase of metabolism: the complex molecules such as polysaccharides or proteins, are converted into simple molecules (ethanol, CO 2, NH 3 …). The catabolic pathways release energy, some of it is recovered, mainly in the form of certain nucleotides such as ATP, NADH and FADH2, and the rest is dissipated as heat. Routes tend to be convergent, ie, from several different precursors are formed the same products.
· Anabolism
This is the stage of biosynthesis: from simple precursors and nutrients are obtained complex molecules (proteins, nucleic acids …). Anabolic pathways require energy provided by molecules such as ATP or NADPH or external energy sources such as light. They are generally divergent paths: from specific metabolites formed many final products.
Enzymes
A common feature of all metabolic reactions is that they tend to run very slowly, even if they are energetically favored, ie, although the reaction products (P) have a lower free energy of the reactants or substrates (S) .
This is because, for the reaction to be completed in either sense (S? P or P? S), it must reachtransition state in which chemical groups are aligned, forming electric charges to be reordered links and carry out other changes that require a high activation energy.
The reaction rate can be increased in two ways:
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Raising the temperature, ie, increasing the average kinetic energy of molecules (the heat). This method increases the fraction of molecules whose energy exceeds the activation, but is impractical, because the cells are essentially isothermal machines, ie they operate at constant temperature.
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Searching alternative paths of the reaction with a lower activation energy
This method relies on molecules known as catalysts that lower the “height” of the transition state and allow him to access many molecules that have little energy. Catalysts increase the rate of reaction without being consumed in the process, without altering the final calculation of free energy of the reaction if a reaction is not spontaneous without catalyst, neither will be with him.
Most catalysts have nature and are known as protein enzymes, but they have also discovered catalytic RNA molecules called ribozymes.
Some enzymes have a classical name, which usually is formed by adding the suffix-ase to the name of the substrate. Thus, urease catalyzes the hydrolysis of urea. So-called systematic name, however, identifies both the substrate and the type of reaction catalyzed. According to this reaction, enzymes are categorized in six classes and their subdivisions, all be numbered in a specific way.
Properties of enzymes
To understand how enzymes reduce the activation energy is necessary to know especially four of its features:
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Center active
Metabolic reactions occur in crevices of the surface of enzymes called active sites. All enzyme has one or more active sites, usually cover no more than three or four amino acids, which are often widely separated in the primary structure of the enzyme. The key point in the action of an enzyme is the binding of substrate (S) to the active site amino acids, thus forming an enzyme-substrate (ES).
After the chemical reaction occur originates enzyme-product complex EP).
Finally, the product P is released, leaving the enzyme ready for a new cycle:
These three stages are reversible S molecules may have to be transformed into P, P molecules that become molecules S and S or P to join the enzyme and released before undergoing any change. The predominance of one reaction or another depend on the final ratio of S and P to make minimum free energy of the system, the enzyme simply accelerates the achievement of that balance.
· Saturation with substrate
ES complex formation was derived as a result of experiments in which they prepared several test tubes with the same amount of free enzyme E and were added progressively increasing amounts of its substrate S. It would then be expected that the initial rate of reaction of each tube (as measured by the amount of product P formed in the first moments) also increased progressively as the balance of the reaction 
would move to the right as it grew the concentration [S].
However, when [S] is very high, all the enzyme molecules rapidly form complex ES, and an additional increase of [S] has no effect on the initial velocity: extra S molecules will have to wait for the release of the product P and the enzymes become available to join them. It has been a top speed, and then says that the enzyme is saturated with its substrate.
· Effectiveness
The reactions catalyzed by enzymes are 10 5-10 17 times faster than the corresponding reactions catalyzed.
· Specifications
The enzymes are very specific in two ways:
o The enzyme acts only on a particular substrate or on a group of them with some common denominator. By contrast, inorganic catalysts can act on many different substances.
Add specificity of action and clear substrate
or only occurs a chemical reaction without side reactions or byproducts. That is, in enzyme reactions is given a yield of 100%. Instead, an artificial catalyst rarely reaches a yield of 90%.
Enzyme kinetics
For a fixed concentration of enzyme, the initial velocity
V 0 of many enzymatic reactions (the amount of product formed in the first minute) hyperbolic varies with the substrate concentration [S]
As increases [S], the V 0 increases. At first increases almost linearly, but when [S] is high, the enzyme is saturated with the substrate, and V 0 will just grow: it has reached the maximum velocity (V max) of the reaction.
The relationship between V 0 and [S] can be expressed by the mathematical equation formulated in 1913 by the German biochemist Leonor Michaelis (1875-1949) and the Canadian Medical Maud Leonora Menten (1879-1960): 
In this equation, K M is a constant characteristic of the enzyme and its substrate, known as the Michaelis constant. For simple reactions, K M can be interpreted as a measure of the affinity of the enzyme to its substrate, low K M values indicate that the ES complex is very close, and rarely dissociates without the substrate to react and form the product.
As can be seen in the equation, when [S] = K M, V 0 = 1? 2 V max.
Mechanism of enzyme action
The enumeration of the properties of enzymes raises several questions: why their effectiveness and specificity are so striking?
If the active site is responsible for enzyme activity, why you need the rest of the molecule?
The answer to these questions has two parts, distinct but complementary:
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Rearrangements of covalent bonds
In many enzymes form transient covalent bonds between amino acid residues of the active site and substrate, which raise the energy level of the latter and approaching the transition state. It is also common proton transfer or functional groups between the enzyme and substrate to stabilize a reaction intermediate that otherwise would decompose rapidly, forming reactants rather than products.
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Interactions noncovalent
The effectiveness of an enzyme is based on the drastic decrease of the activation energy (AG ‡) that catalyzes the reaction. ‡ AG But to reduce a certain amount the system must purchase energy amount. Most of that energy comes from the so-called fixed energy (AG B), which is released to form a large number of weak interactions such as hydrogen or ionic bonds between the substrate and enzyme.
The need for multiple noncovalent bonds explains that an enzyme is much more than their active site: the enzyme should provide functional groups to establish links, broken down by its tertiary structure. It also accounts for their specificity: only the substrates that have a particular structure may interact with functional groups of the enzyme orderly arranged.
In this diagram reflects the changes in energy of a reaction in the absence (blue) and presence (red) of enzyme. The activation energy necessary to achieve a state of transition, represented by ‡, is lower in the second case (AG ‡cat) in the first (AG ‡nocat).
The difference between the two is the energy of AG B setting.
Factors affecting enzyme activity
The enzyme activity can be disrupted by various physical factors such as pH or temperature.
A change in pH can affect the electrical charge of side chains of amino acids to interact with the substrate, so that every enzyme has an optimum pH or pH range where its activity is maximal.
An extreme pH or temperature can denature the protein.
You can also change the enzyme activity by the presence of inhibitors, molecules that slow or stop the reactions and are classified into two categories:
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Irreversible inhibitors
They bind to their activity, usually covalently to a group of essential enzyme that destroys or permanently unusable. They include many drugs and poisons, such as nerve gas.
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Reversible inhibitors
They form non-covalent bonds. They can be:
or competitive inhibitors.
They resemble the substrate and bind to the active site of the enzyme, but do not react. Reduce the affinity of the enzyme for its substrate (K M increases), but do not affect the speed of the reaction simply increasing the concentration of substrate for the enzyme operates normally.
acompetitivos or inhibitors.
Fixing only the ES complex, not the free enzyme E. The enzyme-substrate-inhibitor (ESI) is catalytically inactive, so the speed decreases, but also decreases the KM.
or mixed inhibitors.
They bind to both E and ES, but never to the active site. Inhibitor binding reduces both the affinity of the enzyme for its substrate (ie, increases KM) and the maximum speed of the reaction.
Cofactors and coenzymes
The enzyme activity can be affected not only by physical or chemical factors but also by the presence ofnon-protein substances, usually of low molecular mass, called cofactors.
If the cofactors are essential for enzymatic activity, the complete enzyme is called a holoenzyme, and its protein part (catalytically inactive by itself) that of apoenzyme.
A cofactor may be organic or inorganic nature, some enzymes require both.
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Inorganic cofactors
These metal ions such as Fe 2 +, Cu +, Mg 2 + or Zn 2 +, which is only needed in daily quantities of milligrams or micrograms. Some may act as a bridge group, joining both the substrate and the active site of the enzyme. Others can attract electrons from a substrate (changing, for example, ion Fe 3 + to Fe 2 +) to sell them to another molecule. Finally, some ions such as iron or copper, by itself possess some catalytic activity, which, however, is greatly amplified by the protein.
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Organic or organometallic cofactors
They are known as coenzymes if molecules weakly attached to the apoenzyme, if the union is strong (covalent) are called prosthetic groups.
In general, these molecules act as intermediaries between carriers enzymes that catalyze electron transfer reactions or functional groups. Each class has its particular coenzyme reaction that is consumed by a set of enzymes and is regenerated by a different set.
Many coenzymes are modified water-soluble vitamins, but vitamins are coenzymes substances such as ATP or coenzyme Q also is not water soluble.
Regulation of enzyme activity
All the complex network of metabolic reactions occur in a tiny cell, and each requires a different enzyme reaction. Often, the same metabolite is part of different metabolic pathways, if all running at the same time compete with each other, which would make them inefficient. In addition, the rate of nutrient intake or biosynthesis of macromolecules to be adapted each time to the needs of the cell. Finally, cell differentiation in a multicellular organism requires that each cell type different enzymes work.
For all these reasons, the enzyme activity has to be properly regulated. This regulation occurs at two levels:
Modification of the activity of key enzymes
The regulatory action of metabolism is usually located in the enzymes that catalyze reactions that are at the beginning of a metabolic pathway. There are two main mechanisms:
or allosteric transitions.
The three-dimensional structure of the enzyme undergoes modifications induced by the binding of a molecule, the effector or modulator, at a location other than the active site. Sometimes, the modulator stimulates enzyme activity, and there is talk of apositive modulator or activator, more often, the modulator acts as a mixed inhibitor and is known as a negative modulator.
Often, the positive modulator is the substrate itself, and the negative end product of a metabolic pathway.
or covalent modulation.
It is characteristic of enzymes that can exist in two forms, inactive and active, interconvertible by covalent bonding, for example, phosphoryl groups; this union is catalyzed by enzymes called kinases.
Changing the amount of enzyme
A second level of regulation is to destroy in lysosomes or in structures called proteasomes to the enzymes responsible for producing in excess of a product and in manufacturing in the ribosomes cell enzymes that precisely at the time.
Respiration and fermentation
Traditionally, catabolic processes are grouped into two broad categories, known as respiration and fermentation.
However, there is a formal rating, since many metabolic reactions are common to fermentations and respiration.
Respiration is a chemical process that occurs in all cells, namely the combustion of hydrocarbon compounds, preferably glucose, which can be symbolized by the following overall equation:
On the global equation of respiration of glucose can enter the states of oxidation of the carbon atoms involved, calculated as the number of direct links with the oxygen minus the number of direct links with hydrogen:
The net oxidation state of glucose, as regards the carbon atoms is 0, while that of the six molecules of CO 2 is 6 × (+4) = +24. This means that carbon atoms have been oxidized: its links have transferred a total of 24 electrons, which have gone to other links with more “greed” by these electrons.
The “eagerness” or electron affinity can be quantified by the redox potential, which is nothing more than a voltage, a measure of the potential energy capable of displacing electrons from some links to others. The electrons, having negatively charged molecules tend to move to a more positive redox potential.
A substance that can exist in two forms, oxidized (eg, NAD +) and reduced (NADH) is a redox couple (the couple NAD + / NADH in this case). The tendency of the oxidized form to gain electrons and become reduced is measured by its oxidation-reduction potential or redox potential, which is represented by E and is expressed in millivolts (mV).
If breathing combustion were a mere electrons give a single large jump between glucose and O 2 and this quantum leap responsible for the sudden release of energy as heat and light. This is not the case, as in respiration glucose is broken down into small steps and electrons enzymatically controlled sagging “down” step by step, through coenzymes such as NAD and cytochromes, spaced from each other by small differences in redox potential . Thus, release energy in an amount comparable to that required for the synthesis of ATP.
Consequently, respiration involves the breakdown of organic molecules to carbon atoms that reach the highest state of oxidation, corresponding to CO2, over several steps that release energy in small amounts.
The role of O 2 is intended as a final acceptor of electrons from the C – H of organic nutrient, and incorporate them into bonds O – H of the water. It is called aerobic respiration.
Some bacteria use alternative final acceptor, such as SO4 2 – (reduced to S or H 2 S), Fe 3 + ion (which happens to Fe 2 +), NO 3 – (reduced to NO 2 – and even NH 3) or the CO 2 (which is reduced to CH 4). The type of breathing that carry out these bacteria are called anaerobic respiration.
If the final electron acceptor was not an inorganic substance, such as alternative acceptors 02 or above, but another organic substance from the electron donor molecule itself catabolic process anaerobic and would logically be called fermentation.
Among the most important are the fermentation and lactic alcohol, which meets the following global equations adjusted:
Catabolism reactions include essentially three main routes:
glycolysis, the route of the pentose phosphate and Krebs cycle.
One of the most remarkable discoveries of the first half of the twentieth century was that the respiration and alcoholic fermentation and lactic share reactions to the first of these routes.
Glycolysis
Glycolysis is the most universal metabolic pathway; is detected in virtually all cells, both prokaryotes and eukaryotes. Because of its discoverers, is also often known as the Embden-Meyerhof-Parnas or route EMP.
In glycolysis, a glucose molecule is split into two pyruvate-ionized form of three-carbon compound called pyruvate, through a chain of ten reactions catalyzed by enzymes (from E1 to E10).
By glycolysis, the cell gets high-energy molecules such as NADH and ATP from glucose oxidation. This oxidation affects an aldehyde group (- CHO), in the course of the reactions catalyzed by enzymes central E6 and E7 of the above sequence yields two electrons as a hydride ion H-and accepts an oxide anion O2- , becoming a carboxylate group (- COO-):
The NAD + can then collect the ion: H-and form NADH, while the remaining energy can be used to convert one molecule of ADP into ATP.
To be the reaction of oxidation, the glucose molecule is split into two triose. This is because glucose has a single aldehyde group in the carbon one, if only oxidize the carbon, the resulting molecule would retain almost all of the energy of the original glucose. The breakdown of the hexose provides two oxidizable aldehyde groups, which doubles the performance of the process.
The intermediates of glycolysis (the molecules located between glucose and pyruvate) are covalently attached phosphoryl groups (PO3 -), giving them a negative charge and thus can not cross the cell membrane, which lacks transporters for phosphorylated sugars, or leave the cell. In addition, the binding of phosphoryl groups to the active sites of enzymes fixing supplies energy which helps to lower the activation energy, also increasing the effectiveness of the reactions.
The cleavage and phosphorylation of the hexose produced intermediaries, including six of the 13 necessary metabolic precursors for the synthesis of macromolecules. Indeed, glycolysis is a route amphibolic-that is, involved in catabolic and anabolic processes, “since most of their reactions are reversible and can be used in processes that generate hexoses from small molecules.
In glycolysis can distinguish two phases:
Preparatory 1.Fase
During this phase the hexoses is ‘prepared’ for the key reaction of the route, that is, for the oxidation of aldehyde groups of two triose phosphates through the following steps:
or phosphorylation of glucose
Glucose enters the cell by facilitated diffusion (passive transport) and in doing so the hydroxyl-OH group of carbon 6 receives a phosphate group of ATP turning into glucose 6-phosphate (and may not leave the cell).
o Preparation of the splitting of the hexose
For the hexose molecule is divided into two triose previously phosphorylated in position 3 must be phosphorylated not only at carbon 6, but also in 1.
This requires:
– That glucose 6-phosphate is isomerice to fructose 6-phosphate
– That there is a second phosphorylation, which is spent
another molecule of ATP and forms fructose 1,6-bisphosphate
o Training of two phosphorylated triose
Opens the ring of fructose 1,6-bisphosphate, and then breaks the link between carbons 3 and 4. They originate and glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.
The carbonyl group of the ketone does not rust as easily as the aldehyde, in the absence of a C – H. Therefore, dihydroxyacetone phosphate is isomerized to a second molecule of glyceraldehyde 3-phosphate.
2.Fase benefits
Paradoxically, a route such as glycolysis, intended to produce ATP, start spending it: the first phase will invest two molecules of ATP, which raise the free energy content of intermediaries. The initial investment should be recovered in the second phase, together with the relevant “interests”, hence is known as a phase of benefits to this set of five responses that occurs twice, since a glucose molecule is split into two glyceraldehyde 3-phosphate.
Is a sequence of two events:
o The glyceraldehyde 3-phosphate is oxidized by the enzymatic transfer of a hydride ion (: H -) from the NAD + aldehyde group. The NAD + is thus reduced to NADH, but the aldehyde group is not oxidized directly to a carboxylate group, but the acyl phosphate of 1,3-bisphosphoglycerate.
The acyl phosphate of 1,3-bisphosphoglycerate is converted to the carboxylate group of 3-phosphoglycerate by transferring a phosphoryl the ADP, forming ATP.
oel fosfoester link left in the third carbon of 3-phosphoglycerate has a relatively low energy of hydrolysis. To transfer the phosphoryl group to ADP and ATP restore consumed in the preparatory phase is first necessary to move the link from carbon 3 to carbon 2, making the 3-phosphoglycerate in2-phosphoglycerate.
After this rearrangement the central carbon is oxidized to 2-phosphoglycerate, which is converted to phosphoenolpyruvate, high-energy phosphorylated compound.
Here are the phosphoryl group from this high-energy compound to ADP, thereby forming ATP and pyruvate
You can obtain the global equation of glycolysis by adding member to member reactions that make up and simplifying the common terms on both sides of it. Taking into account that in the preparatory phase will consume two molecules of ATP, but at the stage of profit, which is given in duplicate, there are four, the result is: 
The rate of glycolysis described takes place in the cytosol of most prokaryotes and eukaryotes. The most notable exception relates to plants, where there is also in chloroplasts. Although enzymes that catalyze the reactions of the pathway may differ from one cell to another, the end result is the same in all cases.
Many carbohydrates other than glucose ultimately enter into glycolysis, having been transformed into one of the intermediaries in the path:
· The intracellular reserve polysaccharides such as glycogen are mobilized within the cell by enzymes that extract the remains of glucose, one by one, in the form of glucose 1-phosphate, which is converted into glucose 6-phosphate .
· The ingested carbohydrates in the diet, such as starch, lactose or sucrose, are hydrolyzed by the action of digestive enzymes called hydrolases. The resulting monosaccharide such as fructose, galactose … Cross the intestinal epithelium and, after being transported to cells, are incorporated in glycolysis and are phosphorylated and become, finally, glucose 6-phosphate or fructose 6-phosphate.
Pathways after glycolysis
The products of glycolysis: pyruvate, NADH and some intermediates like glucose 6-phosphate can follow several paths:
1.Ruta of the pentose phosphate or phosphogluconate
In her part of the glucose 6-phosphate produced in glycolysis is ‘deviant’ from the path and oxidized exclusively in the cytosol with the following functions:
oUtilizar five of the six carbons of glucose to synthesize an pentose, ribose 5-phosphate, which is an essential component of the nucleotides and nucleic acids.
oProducir NADPH as a source of electrons needed to synthesize fatty acids, cholesterol and steroid hormones.
oMetabolizar pentoses from the digestion of nucleic acids and turn them into glycolysis intermediates, such as glyceraldehyde 3-phosphate.
2.Camino of pyruvate and NADH in anaerobic
In the process of oxidation of organic compounds are released electrons that reduce NAD + to NADH. Because cells have a limited amount of NAD +, NADH must be recycled to regenerate. If it had reduced O 2 taken electrons from NADH and NAD + to oxidize it, but in anaerobic cells lack oxygen and use the same pyruvate as an electron acceptor (fermentation)
to be reduced to products such as lactate (lactic fermentation ), ethanol (fermented alcohol), propionate or acetone
3.Camino of pyruvate and NADH aerobically
Most eukaryotic cells and a large number of bacteria are aerobic. For these organisms, glycolysis is only the first stage of complete degradation of glucose by respiration, a process in which the pyruvate formed in glycolysis instead of being reduced to lactate or other product of fermentation, is oxidized to form CO2. Consequently, more electrons are released that are covered by acceptors such as NAD +. The regenerates NAD + consumed NADH by transferring electrons along a sequence of conveyors, called respiratory chain, until the O 2. The process releases large amounts of energy, which is used as ATP.
The oxidation of pyruvate takes place through the Krebs cycle in eukaryotic cells occurs in the mitochondrial matrix.
In addition, the carbon “entering” in this cycle as an acetyl group attached to coenzyme A by a thioester bond, the resulting molecule is acetyl-coenzyme A (abbreviated, acetyl-CoA).
Thus, the pyruvate formed in the cytosol must be transported into the mitochondria.
Can diffuse freely across the mitochondrial outer membrane through porins, but to cross the inner membrane requires the involvement of an active transporter, pyruvate translocase, which exchanges pyruvate by OH – ions.
Subsequently, pyruvate is converted into acetyl-CoA by pyruvate dehydrogenase (complex of three enzymes and several coenzymes), a process known as oxidative decarboxylation, whose overall equation is:
The oxidative decarboxylation begins with the removal of carbon 1 of pyruvate as CO2. The carbon 2 then becomes an aldehyde group “activated”, as in glycolysis, is oxidized, yielding electrons to NAD +. The energy released in the oxidation is conserved in the thioester bond of acetyl-CoA.
Krebs cycle
The Krebs cycle is central in the metabolic network of the cell. Not only is the gateway for the aerobic degradation of all the molecules that can become an acetyl group, it is also an important source of metabolic precursor molecules such as amino acids, nitrogen bases or cholesterol.
The name of the cycle is due to its principal discoverer, the Germano-British biochemist Hans Adolf Krebs (1900 -1981) who baptized him as citric acid cycle, as the first molecule that forms on the route. It is an acid that has three carboxyl groups, so that the route was also called acid cycle tricarboxylic.
The Krebs cycle consists of a sequence of eight reactions, organized so that a substrate of the first one, oxaloacetate, is the product of the latter.
At every turn in the same place the following processes:
- Enter two carbon atoms in relatively small as acetyl-CoA and H 2 O dosmoléculas in reactions of condensation and moisture.
Salen, in return, two oxidized carbon atoms as CO 2 and two H + protons.
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We give three pairs of electrons to NAD +, formed after three NADH. Sometimes, instead of NADH NADPH is produced.
• A fourth pair of electrons are less energetic than the previous ones and can not reduce NAD +, but the ubiquinone or coenzyme Q, giving (QH2). It uses an enzyme that uses FAD as a cofactor and is anchored to the inner mitochondrial membrane of eukaryotes or the plasma membrane of prokaryotes, whereas the remaining cycle enzymes are soluble in the mitochondrial matrix or cytosol, respectively.
• A the oxidation is coupled to a phosphorylation process which generates ATP.
Instead, in animal cells can form GTP, although this molecule often yields its phosphoryl group to a molecule of ADP, making ATP.
The overall result of the Krebs cycle is:
And so far, the overall equation of the oxidation of one glucose six of CO 2 by the Krebs cycle is:
Cycle intermediates are used as precursors in various anabolic pathways. For example, succinyl-CoA is an intermediate in the synthesis of hemoglobin and chlorophyll. That is, the Krebs cycle is a path amphibolic.
Intermediaries that are used in anabolic processes have to recover or otherwise, will not close the cycle. This is ensured certain processes known as anaplerotic reactions (literally, “fill”), which convert pyruvate or phosphoenolpyruvate to oxaloacetate or malate.
Lipid and protein catabolism
Acetyl-CoA is a converging point in other catabolic processes, and degradation of carbohydrates.
1.Catabolismo fatty acid
The oxidation of fatty acids occurs mainly in peroxisomes of plants and animal mitochondria.
The process involves three steps:
Or activation
The fatty acids with 12 carbons or less freely enter the mitochondria, and there are activated. But the activation of those with 14 carbons or more is normally on the cytosolic side of the outer mitochondrial membrane. To overcome the relative stability of the C – C in a fatty acid its carboxyl group is activated by thioester bond formation with coenzyme A, generating an acyl-CoA (not acetyl-CoA). In the hydrolysis process produces two high-energy bonds of ATP and a pyrophosphate (PPi), whose immediate hydrolysis of two phosphate (Pi) release large amounts of energy that drives the reaction in the direction of the formation of acyl CoA.
or Transportation.
Activated fatty acids on the cytosolic side of the outer mitochondrial membrane must traverse the inner mitochondrial membrane, for which the acyl-CoA formed transiently binds to carnitine, spreading through the so-called acyl-carnitine transporter in the mitochondrial matrix.
or â? Oxidation.
It is a recurring cycle of four steps. The first three involve the oxidation of carbon to the acyl-CoA, the second carbon after the carboxyl group. The fourth step, the cleavage between carbons á and â, generates a molecule of acetyl-CoA and acyl-CoA with two carbons less.
2.Catabolismo of triglycerides or fat
Fatty acids used as fuel to animal cells can be derived from ingested triacylglycerols, the reserves stored in tissues such as adipose or manufactured in the liver from excess carbohydrates in the diet.
Fats are the main energy reserve of the organism, because its carbon atoms are almost completely reduced in comparison with those of the sugars or amino acids, so that oxidation provides more ATP.
Being insoluble in water are hydrated, and can “pack” more in reserve tissues.
To enter cells, triacylglycerols must be hydrolyzed by enzymes called lipases, resulting glycerol and fatty acids:
triacylglycerol + 3 H 2O? Glycerol + 3 fatty acids
Fatty acids are transported into the cell, where they undergo beta-anodised ion.
For its part, glycerol is phosphorylated by an ATP and glycerol 3-phosphate resulting oxidized NADH and dihydroxyacetone phosphate, which enters the glycolysis.
3.Catabolismo protein
In animals amino acids may also contribute to energy production. The plants, however, never uses amino acids as an energy source.
In humans, amino acid oxidation occurs in three different situations:
o During the normal turnover of cellular proteins
Most of the proteins in the cell has a limited life and ends up being degraded. This recycling can renew and rejuvenate cellular structures Cell and get rid of foreign proteins and denatured or misfolded proteins. These latter short-lived and are degraded in the cytosol, in protein complexes called proteasomes, while the longest-lived proteins end up being digested by lysosomes.
or protein-rich diet
Dietary proteins are degraded to amino acids in the intestinal tract by enzymes called proteases.
If ingested amino acids exceed the body needs for protein synthesis, the excess is catabolized, and that amino acids can not be stored.
or during starvation or diseases like diabetes mellitus
In such situations there is no reserve of carbohydrates or these are not used properly, and is used as fuel cell proteins.
The first step in the degradation of amino acids is the separation of its amino group and carbon skeleton.
Generally the amino group is transferred to a-ketoglutarate, thanks to enzymes called transaminases, and glutamate is formed that reaches the liver mitochondria, where the amino group is released as ammonium ion (NH 4+) which is toxic, and liver of many animals is converted to urea (H 2 N – CO – NH2) through a process known as urea cycle.
Urea enters the bloodstream reaches the kidneys and excreted in urine.
The carbon skeleton is oxidized giving Krebs cycle intermediates, particularly acetyl-CoA, a-ketoglutarate, succinyl CoA, fumarate and oxaloacetate. Some amino acids also are degraded to pyruvate.
Respiratory chain: Electron Transport and Oxidative Phosphorylation
The ATP is formed by the addition of a phosphoryl group, ie by phosphorylation–
The ADP. This process is always coupled to the transfer of a pair of electrons between two substances are separated by a redox potential difference of 300 mV.
In substrate-level phosphorylation the electron donor is a metabolite such as glyceraldehyde 3-phosphate, and is a high energy phosphorylated compound, which transfers a phosphoryl group to ADP. The amount of ATP obtained by this method is small.
Most of the ATP made in cellular respiration comes from the reduction of O 2 with electrons donated by NADH or other coenzymes (FADH2, Quinones …) through a system of membrane transporters called respiratory chain.
The process is known as oxidative and phosphorylation depends on the flow of H + or Na + across membranes.
Respiratory chain is located in the cell membrane of bacteria or in the inner mitochondrial membrane of eukaryotic cells. It consists of electron carriers that act sequentially, most of which are integral membrane proteins with prosthetic groups capable of giving and accepting one or two electrons.
It recognizes four classes of these transporters: flavoproteins (FAD), coenzyme Q or ubiquinone (the only electron carrier that is not part of protein, and moves freely through the phospholipid bilayer of the inner membrane mitochondrial), cytochrome (a, 3, b, r. 1) and iron-sulfur centers.
Except for ubiquinone, which diffuses through the lipid bilayer, and cytochrome c, located in space intermembranal, the electron carriers of the respiratory chain supramolecular complexes formed in the inner mitochondrial membrane. In the mitochondria of animal cells are located four major complexes:
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Complexity I or NADH dehydrogenase.
It’s bigger than a ribosome, and transfers electrons from NADH to ubiquinone. Contains FMN as prosthetic groups and at least six FeS centers.
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Complexity II or succinate dehydrogenase.
Is the enzyme that catalyzes the passage of suucinato to fumarate in the Krebs cycle and gives up electrons to ubiquinone. Has FAD and three FeS centers as prosthetic groups.
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Complexity III or bc1 complex.
The middle name is because this complex contains cytochromes by c1, and a special iron-sulfur center called Rieske Center. Transfers electrons from ubiquinone to cytochrome c.
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Complexity IV or cytochrome oxidase.
Contains cytochromes a3 and copper atoms capable of passing the oxidized state (Cu 2 +) to reduced (Cu +). Transfers electrons from cytochrome c to O 2.
In plant cells there is oriented towards the cytosol dehydrogenase that transfers electrons directly from NADH formed in glycolysis to ubiquinone. This enzyme is absent from animal cells.
This lack creates a problem in animal cells: complex I only collects electrons from NADH if this is found in the mitochondrial matrix and therefore, the NADH generated in glycolysis could not, in principle, be reoxidized by the respiratory chain, as it occurs in the cytosol and the inner mitochondrial membrane is impermeable to NADH. However, there are shuttle systems that carry electrons from cytosolic NADH to the respiratory chain via an indirect route. The most active of them, namedmalate-aspartate shuttle, transfers electrons from NADH cytosol to a molecule of NAD + in the matrix, which is reduced to NADH and then transfers its electrons to complex I. The shuttle glycerol 3-phosphate, characteristic of skeletal muscle and brain, passes electrons directly to ubiquinone, “bypassing” the complex I.
The electrons flow from one carrier to another with a more positive redox potential, and this process releases energy that can be coupled to the synthesis of ATP. This coupling takes place through the mechanism suggested in 1961 by the British biochemist Peter Dennis Mitchell who named his proposal with the name of chemiosmotic hypothesis, a process that occurs in two stages:
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Formation of a proton gradient
Complexes I, III and IV of the respiratory chain act as proton pumps: energy advantage provided by the flow of a pair of electrons to eject from the mitochondria 4, 4 and 2 H +,respectively.
In total, 10 H + pumped per NADH gives up electrons to the respiratory chain, and 6 H + are transferred directly if
ubiquinone. The result is the formation of a gradient in proton concentration on either side of the inner mitochondrial membrane.
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Application of the proton gradient to make ATP
Since the H + carry an electrical charge, they accumulate on one side of the membrane originate both an electrical potential difference relative to the other side as a difference in pH, which represents an accumulation of energy. This energy is released when H + flows passively back to the womb. This return occurs through a complex called the inner membrane ATPase or ATP synthase.
Comparing the number of H + that are pumped by the respiratory chain and the number of H + needed to make ATP, we conclude that for each NADH transfers its electrons to generate 3 ATP. However, it should be borne in mind that the gradient of H + is not only used to make ATP. Many carriers operating in the inner mitochondrial membrane directly obtain their energy from H + gradient, not ATP. This is the case of transporters to be introduced into the mitochondrial matrix molecules of ADP and Pi required for the synthesis of ATP, while leaving out the newly formed ATP. These processes consume additional H +, so that the synthesis of three ATP specify, in reality, the flow of 13 H + (10 to complete a lap of the rotor and 3 for the corresponding ADP and Pi).
Every day we discover more cellular processes as energy source is the hydrolysis of ATP, but the flow of H + for the concentration gradient or, in many cases, the flow of Na + ions. We can then extend the analogy of Lipmann and conclude that all known cells have two energy currencies, a soluble-ATP or, sometimes, the GTP-and a membrane-associated proton gradient and / or sodium ions. The ATP synthase would become a sort of “exchange office”, able to convert one currency into another.