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Theory of Intelligent Design, the best explanation of Origins » Molecular biology of the cell » Metabolism » The Citric acid cycle, or Krebs (TCA) cycle

The Citric acid cycle, or Krebs (TCA) cycle

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1 The Citric acid cycle, or Krebs (TCA) cycle on Sat Jan 25, 2014 9:46 am


The Citric acid cycle, or Krebs (TCA) cycle

The universal importance of the TCA cycle, which results in low carbon isotopic fractionation, indicates it may have evolved especially early making it perhaps the most likely carbon fixation pathway for the last common ancestor (LCA). 1

THE CELL Evolution of the First Organism, Joseph Panno, Ph.D.
Glycolysis, the Krebs cycle, and the respiratory chain are all run and assembled by protein enzymes. These metabolic pathways are used by all prokaryotes that are alive today. The glycolytic pathway and the Krebs cycle are located in the protoplasm, while the respiratory chain is located in the cell membrane.

prokaryotes developed two aerobic systems for extracting energy from food molecules: the Krebs cycle, which stores most of the energy as electrons, and the electron transport chain, which uses the energy to make ATP. In eukaryotes, both processes occur in an organelle called the mitochondrion. Consequently, these organelles are responsible for providing the cell with the ATP it needs to power all its biochemical reactions (although a small amount of ATP is provided by glycolysis, which is carried out in the cell’s cytoplasm).

Some cells obtain energy (ATP) by fermentation, breaking down glucose in the absence of oxygen. For most eukaryotic cells and many bacteria, which live under aerobic conditionsand oxidize their organic fuels to carbon dioxide and water, glycolysis is but the first stage in the complete oxidation of glucose. Rather than being reduced to lactate, ethanol, or some other fermentation product, the pyruvate produced by glycolysis is further oxidized to H2O and CO2. This aerobic phase of catabolism is called respiration. In the broader physiological or macroscopic sense, respiration refers to a multicellular organism’s uptake of O2 and release of CO2. Biochemists and cell biologists, however, use the term in a narrower sense to refer to the molecular processes by which cells consume O2 and produce CO2—processes more precisely termed cellular respiration.

Catabolism of proteins, fats, and carbohydrates in the three stages of cellular respiration.
Stage 1: oxidation of fatty acids, glucose, and some amino acids yields acetyl-CoA.
Stage 2: oxidation of acetyl groups in the citric acid cycle includes four steps in which electrons are abstracted.
Stage 3: electrons carried by NADH and FADH2 are funneled into a chain of mitochondrial (or, in bacteria, plasma membrane–bound) electron carriers—the respiratory chain—ultimately reducing O2 to H2O. This electron flow drives the production of ATP.

In the first, organic fuel molecules—glucose, fatty acids, and some amino acids—are oxidized to yield two-carbon fragments in the form of the acetyl group of acetyl-coenzyme A (acetyl-CoA). In the second stage, the acetyl groups are fed into the citric acid cycle, which enzymatically oxidizes them to CO2; the energy released is conserved in the reduced electron carriers NADH and FADH2. In the third stage of respiration, these reduced coenzymes are themselves oxidized, giving up protons (H) and electrons.

The electrons are transferred to O2—the final electron acceptor—via a chain of electron-carrying molecules known as the respiratory chain. In the course of electron transfer, the large amount of energy released is conserved in the form of ATP, by a process called oxidative phosphorylation . Respiration is more complex than glycolysis and is believed to have emerged much later, after the appearance of cyanobacteria. The metabolic activities of cyanobacteria account for the rise of oxygen levels in the earth’s atmosphere, a dramatic turning point in evolutionary history. We consider first the conversion of pyruvate to acetyl groups, then the entry of those groups into the citric acid cycle, also called the tricarboxylic acid (TCA) cycle or the Krebs cycle. We next examine the cycle reactions and the enzymes that catalyze them. Because intermediates of the citric acid cycle are also siphoned off as biosynthetic precursors, we go on to consider some ways in which these intermediates are replenished. The citric acid cycle is a hub in metabolism, with degradative pathways leading in and anabolic pathways leading out, and it is closely regulated in coordination with other pathways.

Production of Acetyl-CoA (Activated Acetate)

In aerobic organisms, glucose and other sugars, fatty acids, and most amino acids are ultimately oxidized to CO2 and H2O via the citric acid cycle and the respiratory chain. Before entering the citric acid cycle, the carbon skeletons of sugars and fatty acids are degraded to the acetyl group of acetyl-CoA, the form in which the cycle accepts most of its fuel input. Many amino acid carbons also enter the cycle this way, although several amino acids are degraded to other cycle intermediates. Here we focus on how pyruvate, derived from glucose and other sugars by glycolysis, is oxidized to acetyl-CoA and CO2 by the pyruvate dehydrogenase (PDH) complex, a cluster of enzymes—multiple copies of each of three enzymes— located in the mitochondria of eukaryotic cells and in the cytosol of bacteria. A careful examination of this enzyme complex is rewarding in several respects. The PDH complex is a classic, much-studied example of a multienzyme complex in which a series of chemical intermediates remain bound to the enzyme molecules as a substrate is transformed into the final product. Five cofactors, four derived from vitamins, participate in the reaction mechanism. The regulation of this enzyme complex also illustrates how a combination of covalent modification and allosteric regulation results in precisely regulated flux through a metabolic step. Finally, the PDH complex is the prototype for two other important enzyme complexes: -ketoglutarate dehydrogenase, of the citric acid cycle, and the branched-chain -keto acid dehydrogenase,
of the oxidative pathways of several amino acids. The remarkable similarity in the protein structure, cofactor requirements, and reaction mechanisms of these three complexes doubtless reflects a common evolutionary origin designer  Smile.

Pyruvate Is Oxidized to Acetyl-CoA and CO2

The overall reaction catalyzed by the pyruvate dehydrogenase complex is an oxidative decarboxylation, an irreversible oxidation process in which the carboxyl group is removed from pyruvate as a molecule of CO2 and the two remaining carbons become the acetyl group of acetyl-CoA. The NADH formed in this reaction gives up a hydride ion (:H) to the respiratory chain , which carries the two electrons to oxygen or, in anaerobic microorganisms, to an alternative electron acceptor such as nitrate or sulfate. The transfer of electrons from NADH to oxygen ultimately generates 2.5 molecules of ATP per pair of electrons. The irreversibility of the PDH complex reaction has been demonstrated by isotopic labeling experiments: the complex cannot reattach radioactively labeled CO2 to acetyl-CoA to yield carboxyl-labeled pyruvate.

The Pyruvate Dehydrogenase Complex Requires Five Coenzymes

The combined dehydrogenation and decarboxylation of pyruvate to the acetyl group of acetyl-CoA requires the sequential action of three different enzymes and five different coenzymes or prosthetic groups—thiamine pyrophosphate (TPP), flavin adenine dinucleotide (FAD), coenzyme A (CoA, sometimes denoted CoA-SH, to emphasize the role of the —SH group), nicotinamide adenine dinucleotide (NAD), and lipoate. Four different vitamins required in human nutrition are vital components of this system: thiamine (in TPP), riboflavin (in FAD), niacin (in NAD), and pantothenate (in CoA). We have already described the roles of FAD and NAD as electron carriers, and we have encountered TPP as the coenzyme of pyruvate decarboxylase


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Citrate Cycle 1

The citrate cycle (Krebs cycle, tricarboxylic acid cycle) plays the central role in metabolism both of eukarya and most prokarya . It is the major site of oxidation of carbon chains from carbohydrates, fatty acids (both entering via acetyl-CoA) and many amino acids to CO2 and water. It supplies NADH as essential substrate for the oxidative phosphorylation in the respiratory chain and thus has a major role in energy metabolism. It also provides intermediates for the synthesis of amino acids and porphyrins . The cycle operates only under aerobic conditions, since it requires the quick reconstitution of NAD+ from NADH by the respiratory chain .In green sulfur bacteria (Chlorobiaceae), some other bacteria and archaea, the ‘reductive citrate cycle’ is operative, which yields acetylCoA by autotrophic CO2 fixation under anaerobic conditions. It resembles the citrate cycle running backwards and substitutes the Calvin cycle. Reduced ferredoxin serves as the main reductant for CO2 fixation. It is speculated that inorganic catalysis of analogous reactions might have played a role in the origin of life on earth.

The citric acid cycle — also known as the tricarboxylic acid cycle (TCA cycle), or the Krebs cycle,[1][2][3] — is a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetate derived from carbohydrates, fats and proteins into carbon dioxide and chemical energy in the form of adenosine triphosphate (ATP). In addition, the cycle provides precursors of certain amino acids as well as the reducing agent NADH that is used in numerous other biochemical reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest established components of cellular metabolism
and may have originated abiogenically. ( i very much doubt so )

The paper: The Puzzle of the Krebs Citric Acid Cycle: Assembling the Pieces of Chemically Feasible Reactions, and Opportunism in the Design of Metabolic Pathways During Evolution
Writers: Enrique Mele´ndez-Hevia, Thomas G. Waddell,2 Marta Cascante , J Mol Evol (1996) 43:293-303

    Of the phosphomalate pathway, which they had eliminated, they write: “…IT COULD BE ARGUED, however, that the feeder P-malate COULD HAVE PLAYED SOME ROLE in earlier metabolism; and thus it IT COULD HAVE BEEN AVAILABLE. It is, in fact, HIGHLY UNLIKELY that some ancient metabolic pathway involving such a compound has vanished without trace (although the original pathway has been lost, such an intermediate COULD HAVE BEEN to other purposes); however, it CANNOT BE STRICTLY DISCARDED and thus, although UNLIKELY, phosphomalate and the [alternative] Krebs cycle structure…MIGHT BE FOUND IN SOME paleospecies as a case of paleometabolism.”Melendez et al conclude: “The Krebs cycle has been frequently quoted as a key problem in the WHAT ALREADY EXISTS.  The most novel resuevolution of living cells, hard to explain by Darwin’s natural selection: How could natural selection explain the building of a complicated structure in toto, when the intermediate stages have no obvious fitness functionality? ……….. In the Krebs cycle problem the intermediary stages were also useful, but for different purposes, and, therefore, its complete DESIGN (Design?) was a very clear case of opportunism. ………..the KREBS CYCLE WAS BUILT through the process that Jacob (1977) called ‘evolution by molecular tinkering,’ stating that EVOLUTION DOES NOT PRODUCE NOVELTIES FROM SCRATCH (Oh? Then how did the first models get there??): IT WORKS ON WHAT ALREADY EXISTS.  The most novel of our analysis is seeing how, with minimal new material, evolution CREATED (I thought evolutionauts weren’t creationists?)  the most important pathway of metabolism, achieving the BEST CHEMICALLY POSSIBLE DESIGN. IN THIS CASE, A CHEMICAL ENGINEER WHO WAS LOOKING FOR THE BEST DESIGN OF THE PROCESS COULD NOT HAVE FOUND A BETTER DESIGN THAN THE CYCLE WHICH WORKS IN LIVING CELLS”

(Astounding. This guy just disproved his own theory. The one he is trying to prove! Is he really a closet intelligent design scientist?)

The citric acid cycle would satisfy this definition of irreducible complexity: it has multiple parts (enzymes); these parts are inter-related, insofar as they constitute a chemical cycle; and finally, if you remove any of the parts, you break the cycle, so the system’s basic function is detroyed.


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The citric acid cycle is a cycle of eight interacting enzymes that catalyze the oxidation of a 2-carbon molecule (an acetyl group) to CO2. The pathway won't work if you remove any one of the enzymes. Thus, it seems on the surface to be an example of an irreducibly complex system. 

However, we have a very good understanding of how the citric acid cycle evolved from simpler pathways. Most species of bacteria don't have a citric acid cycle. Instead they have two separate pathways, reductive and oxidative, that are similar to the left and right halves of the citric acid cycle respectively. We can easily construct a plausible scenario that joins the two branches to create a cycle. Does this mean that we have a good example of the evolution of an irreducibly complex system, thus blowing ID out of the water? 

Of course it does. But the IDiots will never admit it. Instead, they note that such a pathway involves precursors that don't have the same function as the complete citricacid cycle; therefore, the citric acid cycle wasn't really irreducibly complex. In order to be irreducibly complex, sensu Behe, it has to be impossible for it to arise by evolution. 

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Citric acid cycle

[ltr]The citric acid cycle (also known as the tricarboxylic acid cycle, TCA cycle, and as the Krebs cycle) is a series of chemical reactions of central importance in all living cells that utilize oxygen to generate useful energy by cellular respiration. Essentially, the cycle involves converting the potential energy of a variety of nutrients into the readily available energy of adenosine triphosphate (ATP). This cycle is the "power plant" that energizes all metabolism and thus, life itself.
In aerobic organisms, the citric acid cycle is a metabolic pathway that forms part of the breakdown of carbohydrates, fats and proteinsinto carbon dioxide and water in order to generate energy. It is one of three metabolic pathways that are involved in fuel molecule catabolism and adenosine triphosphate production, the other two being glycolysis and oxidative phosphorylation. Glycolysis and oxidative phosphorylation are also tied to the citric acid cycle.
The citric acid cycle also provides precursors for many compounds, such as certain amino acids, and some of its reactions are important in cells performing fermentation reactions in the absence of oxygen.
This key metabolic cycle was established very early in the unfolding plan of creation as the molecules involved, and the set of enzymesthat run the cycle, are essentially the same in all bacteria, fungi, plants, and animals. The implication is that the cycle was well established well before the last universal ancestor of all life. The current consensus is that this cycle predated the advent of free oxygen where it was "run in reverse" (energy was put into the cycle) to assemble important molecules.
The citric acid cycle is the focus of attention of both those advocating design by a supreme being and those opposing such design. Biochemist Michael Behe, in his 1996 book Darwin's Black Box, made the claim that Darwinian evolution cannot account for the biochemical complexity of the living cell, which thus must be the products of intelligent design. The essence of the argument is that aspects of cellular machinery (bacterial flagellum, blood clotting, cellular transport and immune systems, and metabolic pathways, etc.) are irreducibly complex, so that removal of any one part causes the system to break down. Thus, it is inconceivable how this could develop through natural selection. Those opposing Behe's thesis point to an paper by Melendez-Hevia, et al. (1996) purporting to present a feasible scenario for the evolution of the citric acid cycle from simpler biochemical systems.
The citric acid cycle is also known as the Krebs Cycle in honor of Sir Hans Adolf Krebs (1900 - 1981), who proposed the key elements of this pathway in 1937, and was awarded the Nobel Prize in Medicine for its discovery in 1953.[/ltr]
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In essence, the citric acid cycle plays a central role in the manipulation of small carbon-oxygen-hydrogen molecules. This cycle plays two key roles in metabolism.
Running in one direction, the cycle constructs many basic molecules on which the rest of metabolism is based. A metabolic process that builds larger molecules is called anabolism. Running in the opposite direction, the cycle combines small molecules with oxygen and captures the liberated energy to run all of metabolism, breaking down molecules into smaller units in the process. A metabolic process to break down molecules into smaller units is called catabolism. The citric acid cycle is considered an amphibolic pathway because it participates in both catabolism and anabolism.
In practice, a cell runs billions of such cycles simultaneously, most in the energy-generating direction. Bacterial prokaryotes run the cycle both ways in their cytoplasm. In eukaryote cells, such as in humans, this energy-generating cellular respiration is constrained to within the mitochondria, the bacteria-like powerhouses of the cell.
In oxygen-using aerobic organisms, the citric acid cycle is the second step in the breakdown of carbohydrates, fats, and proteins into carbon dioxide and water in order to generate energy. In essence, the citric acid cycle has food molecules fed into it by a preprocessing pathway. A basic food molecule, such as glucose, is first broken down, without oxygen, by a series of steps, into smaller molecules. Some energy is captured as a few ATP molecules during this preprocessing stage. In the absence of oxygen, no more energy can be extracted, and the waste is converted into molecules such as ethanol (alcohol) or lactic acid (involved in the cramp of a muscle cell). In aerobic organisms, the citric acid cycle and subsequent oxidative phosphorylation process generates a large number of ATP molecules.
In carbohydrate catabolism (the breakdown of sugars), the citric acid cycle follows glycolysis, which breaks down glucose (a six-carbon-molecule) into pyruvate (a three-carbon molecule). In eukaryotes, pyruvate moves into the mitochondria. It is converted into acetyl-CoA (acetyl coenzyme A) and enters the citric acid cycle.
In protein catabolism, proteins are broken down by protease enzymes into their constituent amino acids. These amino acids are brought into the cells and can be a source of energy by being funnelled into the citric acid cycle.
In fat catabolism, triglycerides are hydrolyzed to break them into fatty acids and glycerol. In the liver, the glycerol can be converted into glucose via dihydroxyacetone phosphate and glyceraldehyde-3-phosphate by way of gluconeogenesis (carbohydrate catabolism of the glucose can then take place, as above). In many tissues, especially heart tissue, fatty acids are broken down through a process known as beta oxidation, which results in acetyl-CoA that can be used in the citric acid cycle. Sometimes beta oxidation can yield propionyl CoA, which can result in further glucose production by gluconeogenesis in liver.
The citric acid cycle is always followed by oxidative phosphorylation. This process extracts the energy from NADH and FADH2, recreating NAD+ and FAD, so that the cycle can continue. The citric acid cycle itself does not use oxygen, but oxidative phosphorylation does.
The total energy gained from the complete breakdown of one molecule of glucose by glycolysis, the citric acid cycle, and oxidative phosphorylation equals about 36 ATP molecules.
The cycle continues, thousands of times a second. One turn of the cycle turns the glucose fragment into carbon dioxide and water, just as if it had burnt in a flame.

Location of cycle and inputs and outputs

The citric acid cycle takes place within the mitochondrial matrix in eukaryotes, and within the cytoplasm in prokaryotes. There are eight stages in the citric acid cycle.

The reactions of TCAC as they happen in a human cell.
The color scheme is as follows: enzymes, coenzymes, substrate names, metal ions, inorganic molecules, inhibition,stimulation .
* - FAD/FADH2 is covalently attached to SDH
Fuel molecule catabolism (including glycolysis) produces acetyl-CoA, a two-carbon acetyl group bound to coenzyme A. Acetyl-CoA is the main input to the citric acid cycle. Citrate is both the first and the last product of the cycle, and is regenerated by the condensation of oxaloacetate and acetyl-CoA.
A different enzyme catalyzes each of the eight stages in the citric acid cycle, meaning there are eight different enzymes used in the cycle.[/ltr]
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Two carbons are oxidized to CO2, and the energy from these reactions is stored in guanosine triphosphate (GTP), NADH and FADH2. NADH and FADH2 are coenzymes (molecules that enable or enhance enzymes) that store energy and are utilized in oxidative phosphorylation.[/size]
A simplified view of the process: The process begins with pyruvate, producing one CO2, then one CoA. It begins with the six carbon sugar, glucose. It produces 2 CO2 and consumes 3 NAD+ producing 3NADH and 3H+. It consumes 3 H2O and consumes one FAD, producing one FADH+.


Many of the enzymes in the TCA cycle are regulated by negative feedback from ATP when the energy charge of the cell is high. Such enzymes include the pyruvate dehydrogenase complex that synthesises the acetyl-CoA needed for the first reaction of the TCA cycle. Also the enzymes citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, which regulate the first three steps of the TCA cycle, are inhibited by high concentrations of ATP. This regulation ensures that the TCA cycle will not oxidise excessive amount of pyruvate and acetyl-CoA when ATP in the cell is plentiful. This type of negative regulation by ATP is by an allosteric mechanism. (Allosteric refers to the regulation of an enzyme or protein as a result of the binding of a molecule at a site other than the active site.)
Several enzymes are also negatively regulated when the level of reducing equivalents in a cell are high (high ratio of NADH/NAD+). This mechanism for regulation is due to substrate inhibition by NADH of the enzymes that use NAD+ as a substrate. This includes both the entry point enzymes pyruvate dehydrogenase and citrate synthase.


  • Behe, M. J. 1996. Darwin's Black Box. New York: The Free Press.
  • Melendez-Hevia, E., Waddell, T. G., and Cascante, M. 1996. The puzzle of the citric acid cycle. Journal of Molecular Evolution43:293-303.

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5 incomplete reductive TCA cycle on Sun Aug 30, 2015 10:21 pm


incomplete reductive TCA cycle 1

General Background
The complete, oxidative tricarboxylic acid (TCA) cycle plays a central role in the energy metabolism of aerobic organisms. In most autotrophic bacteria and anaerobic archaea, the TCA cycle operates in a reductive, biosynthetic direction (see MetaCyc pathways TCA cycle I (prokaryotic) and reductive TCA cycle I). Some anaerobic archaea such as Thermoproteus tenax, contain an oxidative TCA cycle that uses elemental sulfur or thiosulfate as terminal electron acceptor [Selig94] and reviewed in [Romano96]. Incomplete oxidative or reductive TCA cycles have also been identified in some organisms, including obligate autotrophs and methanotrophs. Although the gene encolding α-ketoglutarate dehydrogenase is absent, or not expressed, these incomplete cycles can still convert pyruvate to necessary biosynthetic intermediates in response to anaerobic, or microaerophilic growth conditions (reviewed in [Wood04]).
Methanogens (anaerobic archaea) lack the ability to perform a complete oxidative or reductive TCA cycle, and biosynthetic intermediates are proposed to be synthesized by incomplete cycles (in [Goodchild04]). Most methanogens use the incomplete reductive TCA cycle for biosynthesis of intermediates (in [Ekiel85]). An incomplete reductive TCA cycle has been shown in the methanogen Methanospirillum hungatei using 13C labeling and NMR, although no enzyme assays were provided [Ekiel83]. It has also been shown in Methanothermobacter thermautotrophicus by radiolabeled succinate incorporation studies [Fuchs78].

About This Pathway
Enzymes of an incomplete reductive TCA cycle have been experimentally demonstrated in the autotrophic methanogen Methanococcus maripaludis [Shieh87] and the pathway is shown here. Acetyl-CoA entering this pathway may be biosynthesized by the acetyl-CoA pathway of autotrophic carbon dioxide fixation (see reductive acetyl coenzyme A pathway) [Ladapo90, Shieh88], or it may be biosynthesized from acetate when this facultative autotroph is grown on acetate (see acetate conversion to acetyl-CoA) [Shieh87]. Acetyl-CoA is converted to pyruvate by pyruvate synthase, and pyruvate is converted to the necessary biosynthetic intermediates oxaloacetate, succinyl-CoA, and 2-oxoglutarate. The later is a precursor of L-glutamate, as indicated by the pathway link.
The acetogenic methanogens Methanosarcina barkeri and Methanosaeta concilii have been shown to contain incomplete oxidative TCA cycles involved in acetate assimilation (in [Weimer79, Smith85, Ekiel85]). Evidence for an incomplete oxidative TCA cycle for amino acid biosynthesis in the cold-adapted (psychrophilic) archaeon Methanococcoides burtonii has been obtained by proteomic analysis, but no enzyme activity assays were provided [Goodchild04].
It should be noted, however, that if current genome-based predictions are verified experimentally, some organisms, such as Methanothermobacter thermautotrophicus, with incomplete TCA cycles might eventually be shown to contain complete cycles. In these cases, other gene products would provide the missing enzyme activity ([Makarova03], and reviewed in [Huynen99]).

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7 Glycolysis and the citric acid cycle on Fri Jan 15, 2016 12:16 pm


Glycolysis and the Citric Acid Cycle: The Control of Proteins and Pathways

Automobiles have incredible engines, cooling systems, drive trains, and so forth, but all of this must be controlled. The accelerator, gears and brakes are essential in automobile design. This is even more true in biology where regulation and control at all levels is crucial and incredibly complex, particularly since so much of the control is performed automatically. At the cellular level, the cell’s machines—the proteins—are controlled at several levels. As one leadingtextbook describes:
A living cell contains thousands of enzymes, many of which operate at the same time and in the same small volume of the cytosol. By their catalytic action, these enzymes generate a complex web of metabolic pathways, each composed of chains of chemical reactions in which the product of one enzyme becomes the substrate of the next. In this maze of pathways, there are many branch points where different enzymes compete for the same substrate. The system is so complex that elaborate controls are required to regulate when and how rapidly each reaction occurs.

Regulation occurs at many levels. At one level, the cell controls how many molecules of each enzyme it makes by regulating the expression of the gene that encodes that enzyme. The cell also controls enzymatic activities by confining sets of enzymes to particular subcellular compartments, enclosed by distinct membranes. The rate of protein destruction by targeted proteolysis represents yet another important regulatory mechanism. But the most rapid and general process that adjusts reaction rates operates through a direct, reversible change in the activity of an enzyme in response to specific molecules that it encounters.

So the cell controls its proteins by controlling how many it creates and destroys, and by confining them to certain compartments. But most directly it controls them directly, as one controls an automobile with the accelerator and brake.

Glycolysis and the citric acid cycle

A great example of all this is the nearly universal glycolysis pathway and citric acid cycle which team up to process food intake. In the glycolysis pathway about a dozen protein enzymes break down the six-carbon sugar known as glucose into two three-carbon molecules. Like a factory production line, each enzyme catalyzes a specific reaction, using the product of the upstream enzyme, and passing the result to the downstream enzyme. If just one of the enzymes is not present or otherwise not functioning then the entire process doesn’t work.

In addition to breaking down glucose, glycolysis also produces energy-carrying molecules called ATP. These are in constant demand in the cell as they are used wherever energy is needed. Like most pathways, glycolysis is interconnected with other pathways within the cell. The molecular products of glycolysis are used elsewhere and so the rate at which the glycolysis pathway proceeds is important. Too fast and its products won’t be useful, too slow and other pathways have to slow down.

Glycolysis is regulated in a number of ways. The first enzyme in the glycolysis pathway is regulated by its own product. This enzyme alters glucose to form an intermediate product, but if the rest of the pathway is not keeping up then the intermediate product will build up, and this will cause the enzyme to shut down temporarily. The enzyme is designed to be controlled by the presence of its product.

Two other enzymes in the pathway have even more sophisticated regulation. They are sensitive to a number of different molecules which either increase or decrease the enzyme activity. For example, these enzymes are partly controlled by the energy level of the cell. This makes sense since glycolysis helps supply energy to the cell. A good indicator of the cell’s energy level is the relative concentrations of ATP and spent ATP. High levels of ATP indicate a strong energy supply. Hence the enzyme activity is inhibited (and therefore the glycolysis pathway is slowed) when ATP is abundant. But high levels of spent ATP counteract this effect.

How do these molecules control enzyme activity? The molecules are tiny compared to the big enzymes they control. Just as a small key is used to start up and turn off a big truck, so too these small molecules have big effects on their target enzyme. And just as the truck has an ignition lock that can be turned only by the right key, so too the enzyme has several docking sites that are just right for a particular small molecule, such as ATP.

Not only does ATP fit just right into its docking site, but it perturbs the enzyme structure in just the right way so as to diminish the enzyme activity. There is another docking site that only a spent ATP will fit into. And if this occurs then the enzyme structure is again perturbed just right so as to encourage activity and reverse the ATP docking effect.

Glycolysis and the rest of the cell

Glycolysis and the citric acid cycle do not merely create energy for the cell. Just as an oil refinery also produces a range of petroleum products, glycolysis and the citric acid cycle, in addition to producing energy, spin off a series of essential biochemical components needed by the cell. This figure illustrates how these pathways produce nucleotides, lipids, amino acids, cholesterol and other molecules.

In fact glycolysis and the citric acid cycle exist within a complex web of chemical pathways within the cell. These many pathways interaction with each other in many ways, as shown in this wire chart (glycolysis and the citric acid cycle are shown in red).

Sometimes a three dimensional view, that can be rotated, helps to understand the interactions between these many pathways.

This design is complex at many levels. At the molecular level, there is the precise control of the protein enzymes. At the pathway level, there is the interaction between the enzymes. And at the cellular level there is interactions between the different pathways. And all of this has nothing in common with evolution’s naïve, religiously-driven, dogma that biology must be one big fluke. As one evolutionist admitted (one of the textbook authors):
We have always underestimated cells. Undoubtedly we still do today. But at least we are no longer as naive as we were when I was a graduate student in the 1960s. Then, most of us viewed cells as containing a giant set of second-order reactions: molecules A and B were thought to diffuse freely, randomly colliding with each other to produce molecule AB—and likewise for the many other molecules that interact with each other inside a cell. This seemed reasonable because, as we had learned from studying physical chemistry, motions at the scale of molecules are incredibly rapid. … But, as it turns out, we can walk and we can talk because the chemistry that makes life possible is much more elaborate and sophisticated than anything we students had ever considered. Proteins make up most of the dry mass of a cell. But instead of a cell dominated by randomly colliding individual protein molecules, we now know that nearly every major process in a cell is carried out by assemblies of 10 or more protein molecules. And, as it carries out its biological functions, each of these protein assemblies interacts with several other large complexes of proteins. Indeed, the entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each of which is composed of a set of large protein machines. […]

Why do we call the large protein assemblies that underlie cell function protein machines? Precisely because, like the machines invented by humans to deal efficiently with the macroscopic world, these protein assemblies contain highly coordinated moving parts. Within each protein assembly, intermolecular collisions are not only restricted to a small set of possibilities, but reaction C depends on reaction B, which in turn depends on reaction A—just as it would in a machine of our common experience. […]

We have also come to realize that protein assemblies can be enormously complex. … As the example of the spliceosome should make clear, the cartoons thus far used to depict protein machines vastly underestimate the sophistication of many of these remarkable devices. [Bruce Alberts, “The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists,” Cell 92 (1998): 291-294.]

But the dogma remains. Evolutionists insist that evolution must be a fact and they use dozens of religious arguments to make their case. In the next moment they turn around and insist it is all about science. The result is pathetic science, such as the journal paper that tried to explain the citric acid cycle as “evolutionary opportunism.” Religion drives science, and it matters.

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