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ElShamah - Reason & Science: Defending ID and the Christian Worldview

Otangelo Grasso: This is my library, where I collect information and present arguments developed by myself that lead, in my view, to the Christian faith, creationism, and Intelligent Design as the best explanation for the origin of the physical world.

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ATP: The Energy Currency for the Cell

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1ATP: The  Energy  Currency for the Cell  Empty ATP: The Energy Currency for the Cell Tue Aug 04, 2015 9:04 pm



ATP: The  Energy  Currency for the Cell 1


ATP energy used by the human body requires the hydrolysis of 200–300 moles ATP daily. One  ATP synthase protein produces 600 ATP per second. Each ATP molecule is recycled 2000–3000 times a day. A single cell uses about 15 million ATP molecules per second, recycling all ATP molecules every 20–30 s. The human body produces about 70 kilos of this molecule daily! If you stop making it you couldn’t survive more than 14 hours.

Energy is to biology what money is to economics, the means by which organisms purchase goods and services, and since most of the latter are chemical in nature (e.g., biosynthesis), energy must be supplied in chemical form. A number of small molecules can serve as energy donors for biochemical reactions, and one of these functions as the universal energy currency: adenosine triphosphate, ATP, which is a member of the core set of cellular metabolites. ATP participates chemically in most of the processes that it promotes. The adenosine group serves as a handle that binds to proteins that process ATP, the three phosphoryl groups are the working end of the molecule. The terminal phosphoryl group (sometimes the last two) is split off in the course of energy transfer to give the diphosphate (or the monophosphate, respectively). It is irresistible, albeit inaccurate, to envisage metabolic energy being conserved, or stored, in the “high-energy bonds” that connect the phosphoryl groups. To set the record straight, it is the marked tendency of ATP to give up its phosphoryl groups, either to water or to other molecules, that makes it a suitable vehicle for the transfer of chemical energy. For many purposes, we can assume that biological energetics consists of the processes that generate ATP (and other “energy-rich” metabolites), and those that consume these metabolites. As in economics, the linkage between supply and demand is intensely dynamic. The great highways of energetics, respiration and photosynthesis, keep the ATP/ADP ratio high, far away from equilibrium, and that, in turn, allows ATP to serve as an energy donor, displacing from equilibrium those reactions in which it participates. All biosynthetic processes, and also those that entail movement or transport, are energized either by ATP or by one of the more specialized energy carriers, and the latter are linked to the ATP/ADP couple, as it were by a system of exchange rates. How, then, do organisms make the ATP they require? The two major pathways that generate and regenerate ATP are called oxidative phosphorylation and photophosphorylation—driven by respiration and by light absorption, respectively. Both depend on the operation of chains  of catalytic proteins embedded in a membrane: the inner membrane of mitochondria, the thylakoid membrane of chloroplasts or the plasma membrane of certain bacteria. Just how ATP is produced remained mysterious for many years, until it was discovered that the process is at bottom electrical. Both the respiratory chain, a bucket-brigade of proteins that mediate the oxidation of substrates by oxygen, and the analogous photosynthetic cascade, generate a current of protons across the membrane in which these proteins are inserted. These currents power ATP synthesis, and also serve directly as the source of energy for certain work functions. We can thus think of ATP and the proton current (more precisely, the proton potential) as alternative and interconvertible energy currencies. Some functions are paid for in the one currency, others in its mate. 4

What came first, ATP or the enzymes that use ATP, to make ATP ?

ATP drives proteins that make AMP. ATP drives enzymes that make ADP. ATP drives enzymes that make ATP. ATP drives proteins that make AMP. ATP drives enzymes that make ADP. ATP drives enzymes that make ATP.  ====>>> endless loop.

The Adenine triphosphate (ATP) molecule as energy source is required to drive the enzymes/protein machines that make the adenine nucleic base and adenosine monophosphate AMP, used in DNA, one of the four genetic nucleotides "letters" to write the Genetic Code, and then, using these nucleotides as starting material, further molecular machines attach other two phosphates and produce adenine triphosphates (ATP) - he very own molecule which is used as energy source to drive the whole process.. What came first: the enzymes to make ATP, or ATP to make the enzymes that make ATP?

chemist Wilhelm Huck, professor at Radboud University Nijmegen
A working cell is more than the sum of its parts. "A functioning cell must be entirely correct at once, in all its complexity

The cell is irreducibly complex

ATP: The  Energy  Currency for the Cell  Gfdfew11

A critically important macromolecule—arguably “second in importance only to DNA”—is ATP. ATP  serves as the primary energy currency of the cell (Trefil, 1992, p.93).  ATP is the “most widely distributed high-energy compound within the human body” (Ritter, 1996, p. 301). This ubiquitous molecule is “used to build complex molecules, contract muscles, generate electricity in nerves. All fuel sources of Nature, all foodstuffs of living things, produce ATP, which in turn powers virtually every activity of the cell and organism. Imagine the metabolic confusion if this were not so: Each of the diverse foodstuffs would generate different energy currencies and each of the great variety of cellular functions would have to trade in its unique currency” (Kornberg, 1989, p. 62).
The Structure of ATP
ATP contains the purine base adenine and the sugar ribose which together form the nucleoside adenosine. The basic building blocks used to construct ATP are carbon, hydrogen, nitrogen, oxygen, and phosphorus which are assembled in a complex that contains the number of subatomic parts equivalent to over 500 hydrogen atoms. One phosphate ester bond and two phosphate anhydride bonds hold the three phosphates (PO4) and the ribose together. The construction also contains a b-N glycoside bond holding the ribose and the adenine together.
ATP: The  Energy  Currency for the Cell  7MNPIGS
Adenosine-5'-triphosphate (ATP). 
Color indicates the locations of the dissociable protons of ATP

ATP contains two pyrophosphoryl or phosphoric acid anhydride linkages, as shown below:
ATP: The  Energy  Currency for the Cell  FrjaNM8
ATP  (adenosine-5'-triphosphate)
The triphosphate chain of ATP  contains two pyrophosphate linkages, both of which release large amounts of energy upon hydrolysis.

The two-dimensional stick model of the adenosine phosphate family of molecules, showing the atom and bond arrangement. Phosphates are well-known high-energy molecules, meaning that comparatively high levels of energy are released when the phosphate groups are removed. Actually, the high energy content is not the result of simply the phosphate bond but the total interaction of all the atoms within the ATP molecule.

Adenine would never accumulate in any kind of "prebiotic soup. 2

ATP is an abbreviation for adenosine triphosphate, a complex molecule that contains the nucleoside adenosine and a tail consisting of three phosphates.

ATP: The  Energy  Currency for the Cell  1_cell11
ATP: The  Energy  Currency for the Cell  5nRMkAn
As far as known, all organisms from the simplest bacteria to humans use ATP as their primary energy currency. The energy level it carries is just the right amount for most biological reactions. Nutrients contain energy in low-energy covalent bonds which are not very useful to do most of kinds of work in the cells.

These low energy bonds must be translated to high energy bonds, and this is a role of ATP. A steady supply of ATP is so critical that a poison which attacks any of the proteins used in ATP production kills the organism in minutes. Certain cyanide compounds, for example, are poisonous because they bind to the copper atom in cytochrome oxidase. This binding blocks the electron transport system in the mitochondria where ATP manufacture occurs (Goodsell, 1996, p.74).  
ATP: The  Energy  Currency for the Cell  UiWHAHs
How ATP Transfers Energy
Energy is usually liberated from the ATP molecule to do work in the cell by a reaction that removes one of the phosphate-oxygen groups, leaving adenosine diphosphate (ADP). When the ATP converts to ADP, the ATP is said to be spent. Then the ADP is usually immediately recycled in the mitochondria where it is recharged and comes out again as ATP. In the words of Trefil (1992, p. 93) “hooking and unhooking that last phosphate [on ATP] is what keeps the whole world operating.”

The enormous amount of activity that occurs inside each of the approximately one hundred trillion human cells is shown by the fact that at any instant each cell contains about one billion ATP molecules. This amount is sufficient for that cell’s needs for only a few minutes and must be rapidly recycled. Given a hundred trillion cells in the average male, about 10^23 or one sextillion ATP molecules normally exist in the body. For each ATP “the terminal phosphate is added and removed 3 times each minute” (Kornberg, 1989, p. 65).

The total human body content of ATP is only about 50 grams, which must be constantly recycled every day. The ultimate source of energy for constructing ATP is food; ATP is simply the carrier and regulation-storage unit of energy. The average daily intake of 2,500 food calories translates into a turnover of a whopping 180 kg (400 lbs) of ATP (Kornberg, 1989, p. 65).

The Function of ATP
ATP is uniquely situated between the very-highenergy phosphates synthesized in the breakdown of fuel molecules and the numerous lower-energy acceptor molecules that are phosphorylated in the course of further metabolic
reactions. ADP can accept both phosphates and energy from the higher-energy phosphates, and the ATP thus formed can donate both phosphates and energy to the lower-energy molecules of metabolism. The ATP/ADP pair is an intermediately placed acceptor/donor system among high-energy phosphates. In this context, ATP functions as a very versatile but intermediate energy-shuttle device that interacts with many different energy-coupling enzymes of metabolism. 
The ATP is used for many cell functions including transport work moving substances across cell membranes. It is also used for mechanical work, supplying the energy needed for muscle contraction. It supplies energy not only to heart muscle (for blood circulation) and skeletal muscle (such as for gross body movement), but also to the chromosomes and flagella to enable them to carry out their many functions. A major role of ATP is in chemical work, supplying the needed energy to synthesize the multi-thousands of types of macromolecules that the cell needs to exist.

ATP is also used as an on-off switch both to control chemical reactions and to send messages. The shape of the protein chains that produce the building blocks and other structures used in life is mostly determined by weak chemical bonds that are easily broken and remade. These chains can shorten, lengthen, and change shape in response to the input or withdrawal of energy. The changes in the chains alter the shape of the protein and can also alter its function or cause it to become either active or inactive.

The ATP molecule can bond to one part of a protein molecule, causing another part of the same molecule to slide or move slightly which causes it to change its conformation, inactivating the molecule. Subsequent removal of ATP causes the protein to return to its original shape, and thus it is again functional. The cycle can be repeated until the molecule is recycled, effectively serving as an on and off switch (Hoagland and Dodson, 1995, p.104). Both adding a phosphorus (phosphorylation) and removing a phosphorus from a protein (dephosphorylation) can serve as either an on or an off switch.

How is ATP Produced?

ATP is manufactured as a result of several cell processes including fermentation, respiration and photosynthesis. Most commonly the cells use ADP as a precursor molecule and then add a phosphorus to it. In eukaryotes this can occur either in the soluble portion of the cytoplasm (cytosol) or in special energy-producing structures called mitochondria. Charging ADP to form ATP in the mitochondria is called chemiosmotic phosphorylation. This process occurs in specially constructed chambers located in the mitochondrion’s inner membranes.

An outline of the ATP-synthase macromolecule showing its subunits and nanomachine traits. ATP-synthase converts ADP into ATP, a process called charging. Shown behind ATP-synthase is the membrane in which the ATP-synthase is mounted. For the ATP that is charged in the mitochondria, ATP-synthase is located in the inner membrane.
The mitochondrion itself functions to produce an electrical chemical gradient—somewhat like a battery—by accumulating hydrogen ions in the space between the inner and outer membrane. This energy comes from the estimated 10,000 enzyme chains in the membranous sacks on the mitochondrial walls. Most of the food energy for most organisms is produced by the electron transport chain. Cellular oxidation in the Krebs cycle causes an electron build-up that is used to push H+ ions outward across the inner mitochondrial membrane (Hickman et al., 1997, p. 71).

As the charge builds up, it provides an electrical potential that releases its energy by causing a flow of hydrogen ions across the inner membrane into the inner chamber. The energy causes an enzyme to be attached to ADP which catalyzes the addition of a third phosphorus to form ATP. Plants can also produce ATP in this manner in their mitochondria but plants can also produce ATP by using the energy of sunlight in chloroplasts as discussed later. In the case of eukaryotic animals the energy comes from food which is converted to pyruvate and then to acetyl coenzyme A (acetyl CoA). Acetyl CoA then enters the Krebs cycle which releases energy that results in the conversion of ADP back into ATP.

How does this potential difference serve to reattach the phosphates on ADP molecules? The more protons there are in an area, the more they repel each other. When the repulsion reaches a certain level, the hydrogens ions are forced out of a revolving-door-like structure mounted on the inner mitochondria membrane called ATP synthase complexes. This enzyme functions to reattach the phosphates to the ADP molecules, again forming ATP.

The ATP synthase revolving door resembles a molecular water wheel that harnesses the flow of hydrogen ions in order to build ATP molecules. Each revolution of the wheel requires the energy of about nine hydrogen ions returning into the mitochondrial inner chamber (Goodsell, 1996, p.74). Located on the ATP synthase are three active sites, each of which converts ADP to ATP with every turn of the wheel. Under maximum conditions, the ATP synthase wheel turns at a rate of up to 200 revolutions per second, producing 600 ATPs during that second.

ATP is used in conjunction with enzymes to cause certain molecules to bond together. The correct molecule first docks in the active site of the enzyme along with an ATP molecule. The enzyme then catalyzes the transfer of one of the ATP phosphates to the molecule, thereby transferring to that molecule the energy stored in the ATP molecule. Next a second molecule docks nearby at a second active site on the enzyme. The phosphate is then transferred to it, providing the energy needed to bond the two molecules now attached to the enzyme. Once they are bonded, the new molecule is released. This operation is similar to using a mechanical jig to properly position two pieces of metal which are then welded together. Once welded, they are released as a unit and the process then can begin again.
One of the greatest misconceptions in biology – the so-called energy-rich bond – caused a lot of confusion, until Peter Mitchell (Mitchell, 1966, 1968) showed that oxidative ATP synthesis in mitochondria, chloroplasts and bacteria occurs by reversing an electrochemical gradient. ATP does not drive ion pumps and anabolic reactions because it has an energy-rich bond. It does not have such a bond. ATP drives endergonic reactions because the cell maintains the ATP/ADP + phosphate reaction well on the side of ATP, far from equilibrium (Nichol, 2006). all cells maintain the reaction MgATP → MgADP + phosphate well on the side of MgATP. It is the thermodynamic drive towards equilibrium which is the driving force of all cell events, not any mythical energy in the third phosphate bond of ATP.

A Double Energy Packet

Although ATP contains the amount of energy necessary for most reactions, at times more energy is required. The solution is for ATP to release two phosphates instead of one, producing an adenosine monophosphate (AMP) plus a chain of two phosphates called a pyrophosphate. How adenosine monophosphate is built up into ATP again illustrates the precision and the complexity of the cell energy system. The enzymes used in glycolysis, the citric acid cycle, and the electron transport system, are all so precise that they will replace only a single phosphate. They cannot add two new phosphates to an AMP molecule to form ATP.

The solution is an intricate enzyme called adenylate kinase which transfers a single phosphate from an ATP to the AMP, producing two ADP molecules. The two ADP molecules can then enter the normal Krebs cycle designed to convert ADP into ATP. Adenylate kinase requires an atom of magnesium—and this is one of the reasons why sufficient dietary magnesium is important.

Adenylate kinase is a highly organized but compact enzyme with its active site located deep within the molecule. The deep active site is required because the reactions it catalyzes are sensitive to water. If water molecules lodged between the ATP and the AMP, then the phosphate might break ATP into ADP and a free phosphate instead of transferring a phosphate from ATP to AMP to form ADP.

ATP: The  Energy  Currency for the Cell  TL01B1P

To prevent this, adenylate kinase is designed so that the active site is at the end of a channel deep in the structure which closes around AMP and ATP, shielding the reaction from water. Many other enzymes that use ATP rely on this system to shelter their active site to prevent inappropriate reactions from occurring. This system ensures that the only waste that occurs is the normal wear, tear, repair, and replacement of the cell’s organelles.

Pyrophosphates and pyrophosphoric acid, both inorganic forms of phosphorus, must also be broken down so they can be recycled. This phosphate breakdown is accomplished by the inorganic enzyme pyrophosphatase which splits the pyrophosphate to form two free phosphates that can be used to charge ATP (Goodsell, 1996, p.79). This system is so amazingly efficient that it produces virtually no waste, which is astounding considering its enormously detailed structure. Goodsell (1996, p. 79) adds that “our energy-producing machinery is designed for the production of ATP: quickly, efficiently, and in large quantity.”  

The main energy carrier the body uses is ATP, but other energized nucleotides are also utilized such as thymine, guanine, uracil, and cytosine for making RNA and DNA. The Krebs cycle charges only ADP, but the energy contained in ATP can be transferred to one of the other nucleosides by means of an enzyme called nucleoside diphosphate kinase. This enzyme transfers the phosphate from a nucleoside triphosphate, commonly ATP, to a nucleoside diphosphate such as guanosine diphosphate (GDP) to form guanosine triphosphate (GTP).

The nucleoside diphosphate kinase works by one of its six active sites binding nucleoside triphosphate and releasing the phosphate which is bonded to a histidine. Then the nucleoside triphosphate, which is now a diphosphate, is released, and a different nucleoside diphosphate binds to the same site—and as a result the phosphate that is bonded to the enzyme is transferred, forming a new triphosphate. Scores of other enzymes exist in order for ATP to transfer its energy to the various places where it is needed. Each enzyme must be specifically designed to carry out its unique function, and most of these enzymes are critical for health and life.

The body does contain some flexibility, and sometimes life is possible when one of these enzymes is defective—but the person is often handicapped. Also, back-up mechanisms sometimes exist so that the body can achieve the same goals through an alternative biochemical route. These few simple examples eloquently illustrate the concept of over-design built into the body. They also prove the enormous complexity of the body and its biochemistry.

The Contrast between Prokaryotic and Eukaryotic ATP Production

An enormous gap exists between prokaryote (bacteria and cyanobacteria) cells and eukaryote (protists, plants and animals) type of cells:

...prokaryotes and eukaryotes are profoundly different from each other and clearly represent a marked dichotomy in the evolution of life. . . The organizational complexity of the eukaryotes is so much greater than that of the prokaryotes that it is difficult to visualize how a eukaryote could have arisen from any known prokaryote (Hickman et al., 1997, p. 39).

Some of the differences are that prokaryotes lack organelles, a cytoskeleton, and most of the other structures present in eukaryotic cells. Consequently, the functions of most organelles and other ultrastructure cell parts must be performed in bacteria by the cell membrane and its infoldings called mesosomes.

The Four Major Methods of Producing ATP

A crucial difference between prokaryotes and eukaryotes is the means they use to produce ATP. All life produces ATP by three basic chemical methods only:

oxidative phosphorylation
substrate-level phosphorylation

 In prokaryotes ATP is produced both in the cell wall and in the cytosol by glycolysis. In eukaryotes most ATP is produced in chloroplasts (for plants), or in mitochondria (for both plants and animals). No means of producing ATP exists that is intermediate between these four basic methods and no transitional forms have ever been found that bridge the gap between these four different forms of ATP production. The machinery required to manufacture ATP is so intricate that viruses are not able to make their own ATP. They require cells to manufacture it and viruses have no source of energy apart from cells.

In prokaryotes the cell membrane takes care of not only the cell’s energy-conversion needs, but also nutrient processing, synthesizing of structural macromolecules, and secretion of the many enzymes needed for life (Talaro and Talaro, 1993, p. 77). The cell membrane must for this reason be compared with the entire eukaryote cell ultrastructure which performs these many functions. No simple means of producing ATP is known and prokaryotes are not by any means simple. They contain over 5,000 different kinds of molecules and can use sunlight, organic compounds such as carbohydrates, and inorganic compounds as sources of energy to manufacture ATP.

Another example of the cell membrane in prokaryotes assuming a function of the eukaryotic cell ultrastructure is as follows: Their DNA is physically attached to the bacterial cell membrane and DNA replication may be initiated by changes in the membrane. These membrane changes are in turn related to the bacterium’s growth. Further, the mesosome appears to guide the duplicated chromatin bodies into the two daughter cells during cell division (Talaro and Talaro, 1993).

In eukaryotes the mitochondria produce most of the cell’s ATP (anaerobic glycolysis also produces some) and in plants the chloroplasts can also service this function. The mitochondria produce ATP in their internal membrane system called the cristae. Since bacteria lack mitochondria, as well as an internal membrane system, they must produce ATP in their cell membrane which they do by two basic steps. The bacterial cell membrane contains a unique structure designed to produce ATP and no comparable structure has been found in any eukaryotic cell (Jensen, Wright, and Robinson, 1997).

In bacteria, the ATPase and the electron transport chain are located inside the cytoplasmic membrane between the hydrophobic tails of the phospholipid membrane inner and outer walls. Breakdown of sugar and other food causes the positively charged protons on the outside of the membrane to accumulate to a much higher concentration than they are on the membrane inside. This creates an excess positive charge on the outside of the membrane and a relatively negative charge on the inside.

The result of this charge difference is a dissociation of H2O molecules into H+ and OH– ions. The H+ ions that are produced are then transported outside of the cell and the OH– ions remain on the inside. This results in a potential energy gradient similar to that produced by charging a flashlight battery. The force the potential energy gradient produces is called a proton motive force that can accomplish a variety of cell tasks including converting ADP into ATP.

In some bacteria such as Halobacterium this system is modified by use of bacteriorhodopsin, a protein similar to the sensory pigment rhodopsin used in the vertebrate retina (Lim, 1998, p. 166). Illumination causes the pigment to absorb light energy, temporarily changing rhodopsin from a trans to a cis form. The trans to cis conversion causes deprotonation and the transfer of protons across the plasma membrane to the periplasm.

The proton gradient that results is used to drive ATP synthesis by use of the ATPase complex. This modification allows bacteria to live in low oxygen but rich light regions. This anaerobic ATP manufacturing system, which is unique to prokaryotes, uses a chemical compound other than oxygen as a terminal electron acceptor (Lim, 1998, p. 168). The location of the ATP producing system is only one of many major contrasts that exist between bacterial cell membranes and mitochondria.


Chloroplasts are double membraned ATP-producing organelles found only in plants. Inside their outer membrane is a set of thin membranes organized into flattened sacs stacked up like coins called thylakoids (Greek thylac or sack, and oid meaning like). The disks contain chlorophyll pigments that absorb solar energy which is the ultimate source of energy for all the plant’s needs including manufacturing carbohydrates from carbon dioxide and water (Mader, 1996, p. 75). The chloroplasts first convert the solar energy into ATP stored energy, which is then used to manufacture storage carbohydrates which can be converted back into ATP when energy is needed.

The chloroplasts also possess an electron transport system for producing ATP. The electrons that enter the system are taken from water. During photosynthesis, carbon dioxide is reduced to a carbohydrate by energy obtained from ATP (Mader, 1996, p. 12). Photosynthesizing bacteria (cyanobacteria) use yet another system. Cyanobacteria do not manufacture chloroplasts but use chlorophyll bound to cytoplasmic thylakoids. Once again plausible transitional forms have never been found that can link this form of ATP production to the chloroplast photosynthesis system.

The two most common evolutionary theories of the origin of the mitochondria-chloroplast ATP production system are 1) endosymbiosis of mitochondria and chloroplasts from the bacterial membrane system and 2) the gradual evolution of the prokaryote cell membrane system of ATP production into the mitochondria and chloroplast systems. Believers in endosymbiosis teach that mitochondria were once free-living bacteria, and that “early in evolution ancestral eukaryotic cells simply ate their future partners” (Vogel, 1998, p. 1633). Both the gradual conversion and endosymbiosis theory require many transitional forms, each new one which must provide the animal with a competitive advantage compared with the unaltered animals.

The many contrasts between the prokaryotic and eukaryotic means of producing ATP, some of which were noted above, are strong evidence against the endosymbiosis theory. No intermediates to bridge these two systems has ever been found and arguments put forth in the theory’s support are all highly speculative. These and other problems have recently become more evident as a result of recent major challenges to the standard endosymbiosis theory. The standard theory has recently been under attack from several fronts, and some researchers are now arguing for a new theory:

Scientists pondering how the first complex cell came together say the new idea could solve some nagging problems with the prevailing theory... “[the new theory is]... elegantly argued,” says Michael Gray of Dalhouisie University in Halifax, Nova Scotia, but “there are an awful lot of things the hypothesis doesn’t account for.” In the standard picture of eukaryote evolution, the mitochondrion was a lucky accident. First, the ancestral cell—probably an archaebacterium, recent genetic analyses suggest—acquired the ability to engulf and digest complex molecules. It began preying on its microbial companions. At some point, however, this predatory cell didn’t fully digest its prey, and an even more successful cell resulted when an intended meal took up permanent residence and became the mitochondrion. For years, scientists had thought they had examples of the direct descendants of those primitive eukaryotes: certain protists that lack mitochondria. But recent analysis of the genes in those organisms suggests that they, too, once carried mitochondria but lost them later (Science, 12 September 1997, p. 1604). These findings hint that eukaryotes might somehow have acquired their mitochondria before they had evolved the ability to engulf and digest other cells (Vogel, 1998, p. 1633).

In this brief review we have examined only one cell macromolecule, ATP, and the intricate mechanisms which produce it. We have also looked at the detailed supporting mechanism which allows the ATP molecule to function. ATP is only one of hundreds of thousands of essential molecules, each one that has a story. As each of those stories is told, they will stand as a tribute to both the genius and the enormously complex design of the natural world. All the books in the largest library in the world may not be able to contain the information needed to understand and construct the estimated 100,000 complex macromolecule machines used in humans. Much progress has been made in understanding the structure and function of organic macromolecules and some of the simpler ones are now being manufactured by pharmaceutical firms.

Now that scientists understand how some of these highly organized molecules function and why they are required for life, their origin must be explained. We know only four basic methods of producing ATP: in bacterial cell walls, in the cytoplasm by photosynthesis, in chloroplasts, and in mitochondria. No transitional forms exist to bridge these four methods by evolution. According to the concept of irreducible complexity, these ATP producing machines must have been manufactured as functioning units and they could not have evolved by Darwinism mechanisms. Anything less than an entire ATP molecule will not function and a manufacturing plant which is less than complete cannot produce a functioning ATP. Some believe that the field of biochemistry which has achieved this understanding has already falsified the Darwinian world view (Behe, 1996).

1) http://www.trueorigin.org/atp.php
2) http://reasonandscience.heavenforum.org/t2028-origin-of-the-dna-double-helix#3435
3. Biochemistry, 6th ed. Garrett, page 62
4. Franklin M. Harold in The Way of the Cell, page 57 (Oxford: Oxford University Press, c. 2001, 205.)

Last edited by Admin on Wed Sep 16, 2020 5:07 pm; edited 6 times in total




Life is an all or nothing business

The purine base adenine is one of the four life-essential nucleobases used in DNA, the information storage molecule of the Cell, besides serving as the base for adenine triphosphate, ATP, the energy storage molecule of life.  While it is widely known how important DNA is to store information, less known is how complex the metabolic pathways are to synthesize the four nucleotides and bases used in DNA to form the genetic code.

Its formation derives from a complex pathway using atoms from the amino acids glycine, aspartic acid,  the coenzyme tetrahydrofolate, formate,  the amide group of glutamine, and Bicarbonate HCO-3. In order to recruit these starting materials, they need to be available through the metabolic network which must be fully set up, like the Krebs cycle and Glycolysis.  Adenine is synthesized in a complex biosynthesis pathway requiring at least 14 enzymes. 

Some of these enzymes are multifunctional enzymes. They do not only regulate the overall production rate, but the intermediate products of these multifunctional enzymes are not readily released to the medium but are channeled to the succeeding enzymatic activities of the pathway. Channeling increases the overall rate of these multistep processes and protects intermediates from degradation by other cellular enzymes.

Another smart feat is the fact that it is energetically costly to produce nucleotides from scratch. In order to economize, nucleotides are reconverted through various salvage pathways for re-use. 

Adenine is attached to a ribose sugar forming the nucleobase Adenosine, made up of three parts, the nucleobase, the ribose sugar, and one monophosphate group. 

In order to drive the energy demanding reactions of the enzymes to make adenosine monophosphate AMP, another well-known molecule is required, ATP.  ATP is the " energy currency " of most cellular reactions and contains the very own purine base adenine described above, and the sugar ribose which together forms the nucleoside adenosine. The difference to adenosine monophosphate is that ATP uses three phosphate groups linked by what is known as phosphoanhydride bonds. The breakup of these bonds during cell activity is what generates the energy used in all life forms. For this reason, ATP is a critically important macromolecule—arguably “second in importance only to DNA". In order to get three phosphate groups required in ATP, a second phosphate group has first to be attached to Adenosine monophosphate AMP through a remarkable enzyme, named  Adenylate-Kinase. 

Adenylate-Kinase converts one AMP with the use of ATP into two nucleoside diphosphate forms. The further step, oxidative phosphorylation,  is primarily responsible for the conversion of nucleoside diphosphate ADP into triphosphate forms, ATP through ATP synthase turbines in mitochondria, and photosynthesis. 

The job of Adenylate-Kinase is not only to add one phosphate group to produce Adenosine diphosphate,  but also constantly monitors phosphate nucleotide levels inside the cell, and plays an important role in cellular energy homeostasis. By continually monitoring and altering the levels of ATP and the other adenyl phosphates (ADP and AMP levels) adenylate kinase is an important regulator of energy expenditure at the cellular level. As energy levels change under different metabolic stresses adenylate kinase is then able to generate AMP; which itself acts as a signaling molecule in further signaling cascades. An article in Nature magazine reports its importance:

Adenylate Kinase (AK) is a signal transducing protein that regulates cellular energy homeostasis balancing between different conformations. An alteration of its activity can lead to severe pathologies such as heart failure, cancer and neurodegenerative diseases. Cellular homeostasis is preserved through finely regulated molecular mechanisms, some of them involving macromolecules called metabolic monitors. In particular, these systems control the cellular energy state by generating signaling molecules that counteract energy unbalancing through the stimulation of specific molecular targets. One of these metabolic monitors is adenylate kinase (AK). This enzyme coordinates different signaling pathways, ensuring adequate response to a broad range of functional, environmental and stress stimuli. In such a way, AK plays a key role in the cell and its dysfunction is connected to the onset of several diseases, such metabolic disorders, and cancer. 

It takes a fully setup metabolic network to supply the basic materials and literally an armada of complex enzymes to make adenosine monophosphate AMP, the starting point to make ATP, the energy molecule of the Cell. But it takes ATP along the whole process to make AMP, then Adenylate kinase to make ADP, and in the end, ATP synthase turbines to make ATP. What came first? The metabolic network? the nucleobases? The enzymes to make the nucleobases? ATP to supply energy to the enzymes to make AMP? This is truly a circle without a beginning and no end. A stepwise, gradual process based on prebiotic chemical evolution to produce all this described above is impossible. I think we are once again justified to say, life is an either all or nothing process. 


3ATP: The  Energy  Currency for the Cell  Empty Bioenergetics and Life's Origins Fri Jul 06, 2018 3:40 pm



Bioenergetics and Life's Origins

Since ATP plays a key role in the vital activities of all organisms, analysis of abiogenesis pathways for this compound becomes an important issue within the context of the problem of the origin of life. Abiogenic emergence of ATP (and the adenylic system in general) could be crucial both for the functioning of primitive organisms and the energy supply for the emergence of such organisms.  The discussion of a direct genetic relationship between the abiogenic model and biological mechanisms does not seem justified.

Abiotic formation of nucleosides in a chemical reaction of the bases with sugar molecules turned out to be quite problematic. The yield of purine nucleosides in such reactions was low, while pyrimidine nucleosides were not formed at all. The absence of a realistic mechanism for the specific synthesis of ribose under abiogenous conditions constituted an additional problem, arising both from the low specificity of the formose reaction (which is usually considered an abiotic pathway of sugar formation) and instability of the “desirable” configurations of carbohydrate molecules under the conditions of a model experiment. This complication has not been completely circumvented even today, despite the recent progress in the search for conditions that provide for specific synthesis of various sugars, including ribose. 5

In fact, the gap of prebiotic proposals of the origin of ATP, and the enzyme based synthesis employd by biological Cells is enormous. I would say, not bridgeable.

The complex enzymes required for both the creation and break down of ATP are unlikely to have existed on Earth during the period when life first developed. This led scientists to look for a more basic chemical with similar properties to ATP, but that does not require enzymes to transfer energy. 2 The scientists simulated the impact of  a meteorite with the hot, volcanically-active, early Earth by placing samples of the Sikhote-Alin meteorite, an iron meteorite which fell in Siberia in 1947, in acid taken from the Hveradalur geothermal area in Iceland. The rock was left to react with the acidic fluid in test tubes incubated by the surrounding hot spring for four days, followed by a further 30 days at room temperature. In their analysis of the resulting solution the scientists found the compound pyrophosphite, a molecular 'cousin' of pyrophosphate -- the part of ATP responsible for energy transfer. The scientists believe this compound could have acted as an earlier form of ATP in what they have dubbed 'chemical life'.2

The emergence of phosphate-based biochemistry has been a long-recognised problem in the field of abiogenesis (Gulick, 1955). Phosphorus (P) in the fully oxidised +5 oxidation state, as in contemporary biochemistry, has both limited solubility in water in the presence of many common metal ions . 3

Schreibersite on the early earth: Scenarios for prebiotic phosphorylation
15 June 2016
The formation of phosphorylated biomolecules such as nucleotides remains one of the larger challenges in origins of life research. Ultimately such molecules are necessary for the production of nucleic acids, and thus key to generating self-replicating molecules. These molecules are also necessary for metabolic processes as they form key molecules such as ATP and Coenzyme A. Given the commonplace nature of phosphorus in biology, it would seem that prebiotic chemistry also included phosphorylated molecules. However, the process of phosphorylation under plausible geochemical conditions has been claimed to be stymied by insoluble phosphate minerals that are poorly reactive towards alcohols. Pasek and Lauretta (2005) proposed that the meteoritic mineral schreibersite, (Fe,Ni)3P could have been a viable source of phosphorus on the early earth. This argument was based on the ubiquity
of phosphide minerals in meteorites, especially massive iron meteorites, and the generation of soluble and reactive phosphorus phases from the reaction of water with this mineral. These soluble phosphorus compounds include phosphate, pyrophosphate, phosphite, and hypophosphate typically, and these compounds are formed by free radical reactions. 4

Modeling of Abiotic ATP Synthesis in the Context of Problems of Early Biosphere Evolution
May 13, 2014
—The pathway of adenosine triphosphate (ATP) synthesis in living organisms consists of two autonomous stages; this must be taken into account during the design and analysis of chemical models of the abiogenesis of this key participant of metabolic processes. The first stage is construction of an adenine heterocycle linked to a ribose5phosphate molecule to yield AMP, while the following stage is the attachment of phosphoryl residues to the nucleotide molecule by macroergic phosphoanhydride bonds. Involvement of the same set of precursor molecules in both de novo biosynthesis of AMP and abiogenesis of this nucleotide is a very important issue for the analysis of metabolic pathways. Photochemical matrix systems that convert light energy into macroergic bond energy are functional prototypes of photosynthetic phosphorylation; they are of special interest for the construction of abiotic phosphorylation models. Interaction of substrates with a purely mineral matrix (montmorillonite particles) under UV irradiation resulted in the formation of ATP from ADP and orthophosphate. Micro and nanostructures that formed upon the interaction of the mineral component (sodium polysilicate) with an abiogenic organic pigment (a flavin conjugate with a random amino acid polymer) exhibited phosphorylating activity as well when irradiated with visible light. The properties of AMP and ATP abiosynthesis models investigated are in good accordance with the current views on the environmental conditions of the ancient Earth; evident structural differences exist between these models and the biosynthetic systems in modern organisms. 5

Molecules of adenosine triphosphate (ATP) are central to the process of biological energy conversion at the cellular level. ATP belongs to the structural class of ribonucleoside triphosphates. These molecules are coenzymes, i.e., low molecular weight organic cofactors involved in various reactions catalyzed by enzymes; as well, they serve as chemically activated forms of nucleotides during the synthesis of polymeric RNA chains. In other words, cell metabolism is
impossible in the absence of nucleoside triphosphates because transcription and translation processes, as well as the synthesis of genetic material in the case of RNA viruses, are blocked.

However, ATP occupies a special place even in this unique group of compounds, because it was selected for the role of universal energy currency, that is, for coupling catabolic and anabolic reactions in the cell, in the course of evolution. ATP is one of the primary chemical products (along with reduced nicotine amide coenzyme) in photon energy conversion during photosynthesis. Aerobic and anaerobic oxidation of organic substrates, which are initially produced during photosynthesis, is the source of energy for ATP production in heterotrophic organisms. Energy accumulated in ATP molecules is used for the biosynthesis of various compounds in the cell; it provides for the
transmembrane transport of substances and for mechanochemical processes, including the motility of organisms.

Thermal Energy Storage in Pyrophosphate Bonds

Most chemical energy in cells today circulates in the cytoplasm as ATP. Although cells use ATP to drive synthetic reactions, ATP is not a primary energy source, but rather is an energy transfer molecule that picks up energy from an energy source and then delivers it to energy-requiring reactions. This constant resynthesis (cycling) of ATP inside the cell is revealed by estimates showing that to synthesize 1 g of cell mass requires the energy of about 20–100 g of ATP (Stouthamer 1977). The chemical energy content of ATP is present in the pyrophosphate bonds that link the second and third phosphate groups of ATP. These are anhydride bonds, and their chemical energy is released by energetically downhill group transfer reactions of the phosphate group to other molecules, an activating process called phosphorylation. The second molecule gains chemical energy and can in turn undergo reactions that otherwise will not occur. Classic examples include the formation of aminoacyl-tRNA in protein synthesis, or acetyl-CoA in fatty-acid synthesis.

The question is whether pyrophosphate bond energy could have been a significant source of chemical energy in the reactions leading to the origin of life. In fact, phosphate is such an integral part of all contemporary life that phosphorylation reactions must have been incorporated in primitive metabolic pathways. Baltscheffsky (1996) has argued that this is plausible, in part because pyrophosphate and polyphosphates are readily produced simply by heating inorganic phosphate under anhydrous conditions, a process known to occur under natural conditions. Pyrophosphate-containing minerals, canaphite and wooldridgeite, have been discovered in quarries, albeit in minute quantities and in the form of microscopic crystals. Furthermore, Baltscheffsky found that the coupling membranes of a photosynthetic bacterial species—Rhodospirrilum rubrum—synthesize pyrophosphate instead of ATP. The R. rubrum use the pyrophosphate as an energy source, much as other organisms use ATP.

Despite the ease of capturing thermal dehydration energy as pyrophosphate bonds, a plausible pathway for incorporating it as an energy source in early life has not yet been established. This is well worth further study

Compare the proposed explanation of prebiotic source of energy for metabolism in early cells, with the complexity required by biological Cells, and then we have to ask about how that transition from such a simplistic explanation to the origin of metabolic networks could have occurred. The gap is huge. 

Recent work on the meteorite mineral schreibersite and its analogue Fe3P and the generation of condensed phosphates by Fenton chemistry show a great potential for prebiotic P chemistry but the next question is the plausible formation of a large variety of organophosphates from such sources 5

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828274/
2. https://www.sciencedaily.com/releases/2013/04/130404122234.htm
3. http://sci-hub.tw/https://www.sciencedirect.com/science/article/pii/S0016703713000161?via%3Dihub
4. http://sci-hub.tw/https://www.sciencedirect.com/science/article/pii/S1674987116300640
5. http://sci-hub.tw/https://link.springer.com/article/10.1134/S0016702914130084




Why is ATP the preferred choice for energy carriers?

In the RNA world we already had ATP, GTP, CTP and UTP to make RNA . Why was ATP chosen over the other bases ?

Why did evolution favor ATP and not GTP, TTP or CTP as the powerhouse of the cell for many reactions?  GTP is used in some cases - but only few. TTP and CTP even more rarely.
What gave ATP the advantage so that it became the dominant energy storage house of the cell? 

Why does nature use (in most cases) ATP to couple energy into reactions? Why not GTP or CTP?
(Actually, GTP is used for some processes, but I don't know any reactions that use CTP)
The amount of energy they provide upon hydrolysis into ADP/GDP/CDP and Pyrophosphate is the same.

ATP and GTP - both molecules have extremely similar structures and are quite chemically similar. One is Guanosine Triphosphate, the other is Adenosine Triphosphate. And as you know if you've studied nucleotide structure, Guanosine and Adenosine are quite similar, having only a very minor difference or two between them.

The functional difference between GTP and ATP is that ATP is the main energy currency for cells. ATP is used to carry energy for almost all energy-requiring chemical reactions in almost all cells. GTP can occasionally be used to carry energy, but it is more often used as a signaling molecule, as in G-linked proteins

The answers:

No one is really sure why cells chose to use ATP instead of GTP as their main energy currency. There doesn't seem to be a chemical difference between the two that makes ATP better. I guess it was just useful for cells to use one of these molecules as an energy carrier and another as a signaling molecule, so that they wouldn't get their energy and signaling pathways mixed up, or something. You wouldn't want to be consuming GTP for energy when it's supposed to be sending an important signal after all, would you?

Lastly, The simpler model is to have TWO separate energy molecules:
ONE as a powerhouse (ATP) and
SECOND as a sensor (GTP) and
other minor ones like cAMP/cGMP and ddTTP and such.
This model gives better modulatory control over pathways, rather than have to intermingle and make it extremely confusing chemistry to figure out when ATP would be a sensor versus a powerhouse. 1

There is no reason why ATP is used in the Cell for energy supply,  and GTP for signaling. The naturalists narrative is that:  
" After all with the trial and error, some sort of evolutionary consensus came about which at the end resulted in ATP for energetics and GTP for signaling. ".  

"The behavior of the molecules, a little bit of chance, enough time, and the result is incredibly molecular organization in this catastrophic environment. Very complex structural and functional relationship networks. I think ATP had started a step ahead in this area."

Or maybe, it wasnt chance after all, but a intelligent designer, which choose to organize thins in order to work in an orderly fashion ?

1. https://www.researchgate.net/post/Why_did_evolution_favor_ATP_and_not_GTP_TTP_or_CTP


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