170-450: The citric acid cycle —also known as the Krebs cycle , Szent–Györgyi–Krebs cycle , or TCA cycle ( tricarboxylic acid cycle )—is a series of biochemical reactions to release the energy stored in nutrients through the oxidation of acetyl-CoA derived from carbohydrates , fats , proteins , and alcohol . The chemical energy released is available in the form of ATP . The Krebs cycle
340-482: A cell . The general concept of a chemical reaction has been extended to reactions between entities smaller than atoms, including nuclear reactions , radioactive decays and reactions between elementary particles , as described by quantum field theory . Chemical reactions such as combustion in fire, fermentation and the reduction of ores to metals were known since antiquity. Initial theories of transformation of materials were developed by Greek philosophers, such as
510-470: A double displacement reaction , the anions and cations of two compounds switch places and form two entirely different compounds. These reactions are in the general form: AB + CD ⟶ AD + CB {\displaystyle {\ce {AB + CD->AD + CB}}} For example, when barium chloride (BaCl 2 ) and magnesium sulfate (MgSO 4 ) react, the SO 4 anion switches places with
680-434: A first-order reaction , which could be the disintegration of a substance A, is given by: Its integration yields: Here k is the first-order rate constant, having dimension 1/time, [A]( t ) is the concentration at a time t and [A] 0 is the initial concentration. The rate of a first-order reaction depends only on the concentration and the properties of the involved substance, and the reaction itself can be described with
850-466: A futile cycle . Although fat is a common way of storing energy, in vertebrates such as humans the fatty acids in these stores cannot be converted to glucose through gluconeogenesis as these organisms cannot convert acetyl-CoA into pyruvate ; plants do, but animals do not, have the necessary enzymatic machinery. As a result, after long-term starvation, vertebrates need to produce ketone bodies from fatty acids to replace glucose in tissues such as
1020-736: A single displacement reaction , a single uncombined element replaces another in a compound; in other words, one element trades places with another element in a compound These reactions come in the general form of: A + BC ⟶ AC + B {\displaystyle {\ce {A + BC->AC + B}}} One example of a single displacement reaction is when magnesium replaces hydrogen in water to make solid magnesium hydroxide and hydrogen gas: Mg + 2 H 2 O ⟶ Mg ( OH ) 2 ↓ + H 2 ↑ {\displaystyle {\ce {Mg + 2H2O->Mg(OH)2 (v) + H2 (^)}}} In
1190-623: A "vital force" and distinguished from inorganic materials. This separation was ended however by the synthesis of urea from inorganic precursors by Friedrich Wöhler in 1828. Other chemists who brought major contributions to organic chemistry include Alexander William Williamson with his synthesis of ethers and Christopher Kelk Ingold , who, among many discoveries, established the mechanisms of substitution reactions . The general characteristics of chemical reactions are: Chemical equations are used to graphically illustrate chemical reactions. They consist of chemical or structural formulas of
1360-440: A DNA template from its viral RNA genome. RNA in ribozymes such as spliceosomes and ribosomes is similar to enzymes as it can catalyze chemical reactions. Individual nucleosides are made by attaching a nucleobase to a ribose sugar. These bases are heterocyclic rings containing nitrogen, classified as purines or pyrimidines . Nucleotides also act as coenzymes in metabolic-group-transfer reactions. Metabolism involves
1530-536: A characteristic half-life . More than one time constant is needed when describing reactions of higher order. The temperature dependence of the rate constant usually follows the Arrhenius equation : where E a is the activation energy and k B is the Boltzmann constant . One of the simplest models of reaction rate is the collision theory . More realistic models are tailored to a specific problem and include
1700-500: A chemical reaction are called reactants or reagents . Chemical reactions are usually characterized by a chemical change , and they yield one or more products , which usually have properties different from the reactants. Reactions often consist of a sequence of individual sub-steps, the so-called elementary reactions , and the information on the precise course of action is part of the reaction mechanism . Chemical reactions are described with chemical equations , which symbolically present
1870-423: A constant set of conditions within cells, a condition called homeostasis . Metabolic regulation also allows organisms to respond to signals and interact actively with their environments. Two closely linked concepts are important for understanding how metabolic pathways are controlled. Firstly, the regulation of an enzyme in a pathway is how its activity is increased and decreased in response to signals. Secondly,
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#17327826538972040-429: A cycle of reactions that add the acyl group, reduce it to an alcohol, dehydrate it to an alkene group and then reduce it again to an alkane group. The enzymes of fatty acid biosynthesis are divided into two groups: in animals and fungi, all these fatty acid synthase reactions are carried out by a single multifunctional type I protein, while in plant plastids and bacteria separate type II enzymes perform each step in
2210-446: A ferredoxin-dependent 2-oxoglutarate synthase ( EC 1.2.7.3 ). Other organisms, including obligately autotrophic and methanotrophic bacteria and archaea, bypass succinyl-CoA entirely, and convert 2-oxoglutarate to succinate via succinate semialdehyde , using EC 4.1.1.71 , 2-oxoglutarate decarboxylase, and EC 1.2.1.79 , succinate-semialdehyde dehydrogenase. In cancer , there are substantial metabolic derangements that occur to ensure
2380-399: A few molecules, usually one or two, because of the low probability for several molecules to meet at a certain time. The most important elementary reactions are unimolecular and bimolecular reactions. Only one molecule is involved in a unimolecular reaction; it is transformed by isomerization or a dissociation into one or more other molecules. Such reactions require the addition of energy in
2550-405: A fire-like element called "phlogiston", which was contained within combustible bodies and released during combustion . This proved to be false in 1785 by Antoine Lavoisier who found the correct explanation of the combustion as a reaction with oxygen from the air. Joseph Louis Gay-Lussac recognized in 1808 that gases always react in a certain relationship with each other. Based on this idea and
2720-458: A hydrogen acceptor. Hundreds of separate types of dehydrogenases remove electrons from their substrates and reduce NAD into NADH. This reduced form of the coenzyme is then a substrate for any of the reductases in the cell that need to transfer hydrogen atoms to their substrates. Nicotinamide adenine dinucleotide exists in two related forms in the cell, NADH and NADPH. The NAD /NADH form is more important in catabolic reactions, while NADP /NADPH
2890-499: A known physiologic role in mammalian cells; of note, in cancer, 2-hydroxyglutarate is likely a terminal metabolite as isotope labelling experiments of colorectal cancer cell lines show that its conversion back to alpha-ketoglutarate is too low to measure. In cancer, 2-hydroxyglutarate serves as a competitive inhibitor for a number of enzymes that facilitate reactions via alpha-ketoglutarate in alpha-ketoglutarate-dependent dioxygenases . This mutation results in several important changes to
3060-558: A large group of compounds that contain fatty acids and glycerol ; a glycerol molecule attached to three fatty acids by ester linkages is called a triacylglyceride . Several variations of the basic structure exist, including backbones such as sphingosine in sphingomyelin , and hydrophilic groups such as phosphate in phospholipids . Steroids such as sterol are another major class of lipids. Carbohydrates are aldehydes or ketones , with many hydroxyl groups attached, that can exist as straight chains or rings. Carbohydrates are
3230-404: A larger increase in the entropy of their environments. The metabolism of a cell achieves this by coupling the spontaneous processes of catabolism to the non-spontaneous processes of anabolism. In thermodynamic terms, metabolism maintains order by creating disorder. As the environments of most organisms are constantly changing, the reactions of metabolism must be finely regulated to maintain
3400-472: A membrane. Pumping protons out of the mitochondria creates a proton concentration difference across the membrane and generates an electrochemical gradient . This force drives protons back into the mitochondrion through the base of an enzyme called ATP synthase . The flow of protons makes the stalk subunit rotate, causing the active site of the synthase domain to change shape and phosphorylate adenosine diphosphate —turning it into ATP. Chemolithotrophy
3570-438: A neutral radical . In the second case, both electrons of the chemical bond remain with one of the products, resulting in charged ions . Dissociation plays an important role in triggering chain reactions , such as hydrogen–oxygen or polymerization reactions. For bimolecular reactions, two molecules collide and react with each other. Their merger is called chemical synthesis or an addition reaction . Another possibility
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#17327826538973740-469: A process known as beta oxidation , which results in the production of mitochondrial acetyl-CoA , which can be used in the citric acid cycle. Beta oxidation of fatty acids with an odd number of methylene bridges produces propionyl-CoA , which is then converted into succinyl-CoA and fed into the citric acid cycle as an anaplerotic intermediate. The total energy gained from the complete breakdown of one (six-carbon) molecule of glucose by glycolysis ,
3910-591: A set of xenobiotic-metabolizing enzymes. In humans, these include cytochrome P450 oxidases , UDP-glucuronosyltransferases , and glutathione S -transferases . This system of enzymes acts in three stages to firstly oxidize the xenobiotic (phase I) and then conjugate water-soluble groups onto the molecule (phase II). The modified water-soluble xenobiotic can then be pumped out of cells and in multicellular organisms may be further metabolized before being excreted (phase III). In ecology , these reactions are particularly important in microbial biodegradation of pollutants and
4080-459: A short ancestral pathway, the duplication and then divergence of entire pathways as well as the recruitment of pre-existing enzymes and their assembly into a novel reaction pathway. The relative importance of these mechanisms is unclear, but genomic studies have shown that enzymes in a pathway are likely to have a shared ancestry, suggesting that many pathways have evolved in a step-by-step fashion with novel functions created from pre-existing steps in
4250-530: A source of energy, while switching between carbon fixation and the fermentation of organic compounds. In many organisms, the capture of solar energy is similar in principle to oxidative phosphorylation, as it involves the storage of energy as a proton concentration gradient. This proton motive force then drives ATP synthesis. The electrons needed to drive this electron transport chain come from light-gathering proteins called photosynthetic reaction centres . Reaction centers are classified into two types depending on
4420-413: A vast array of chemical reactions, but most fall under a few basic types of reactions that involve the transfer of functional groups of atoms and their bonds within molecules. This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions. These group-transfer intermediates are called coenzymes . Each class of group-transfer reactions
4590-419: Is oxidative stress . Here, processes including oxidative phosphorylation and the formation of disulfide bonds during protein folding produce reactive oxygen species such as hydrogen peroxide . These damaging oxidants are removed by antioxidant metabolites such as glutathione and enzymes such as catalases and peroxidases . Living organisms must obey the laws of thermodynamics , which describe
4760-450: Is 38 (assuming 3 molar equivalents of ATP per equivalent NADH and 2 ATP per FADH 2 ). In eukaryotes, two equivalents of NADH and two equivalents of ATP are generated in glycolysis , which takes place in the cytoplasm . If transported using the glycerol phosphate shuttle rather than the malate–aspartate shuttle , transport of two of these equivalents of NADH into the mitochondria effectively consumes two equivalents of ATP, thus reducing
4930-571: Is a type of metabolism found in prokaryotes where energy is obtained from the oxidation of inorganic compounds . These organisms can use hydrogen , reduced sulfur compounds (such as sulfide , hydrogen sulfide and thiosulfate ), ferrous iron (Fe(II)) or ammonia as sources of reducing power and they gain energy from the oxidation of these compounds. These microbial processes are important in global biogeochemical cycles such as acetogenesis , nitrification and denitrification and are critical for soil fertility . The energy in sunlight
5100-493: Is an accumulation of citrate and a decrease in substrate for the enzyme. Regulation by calcium . Calcium is also used as a regulator in the citric acid cycle. Calcium levels in the mitochondrial matrix can reach up to the tens of micromolar levels during cellular activation. It activates pyruvate dehydrogenase phosphatase which in turn activates the pyruvate dehydrogenase complex . Calcium also activates isocitrate dehydrogenase and α-ketoglutarate dehydrogenase . This increases
5270-401: Is an organic compound needed in small quantities that cannot be made in cells. In human nutrition , most vitamins function as coenzymes after modification; for example, all water-soluble vitamins are phosphorylated or are coupled to nucleotides when they are used in cells. Nicotinamide adenine dinucleotide (NAD ), a derivative of vitamin B 3 ( niacin ), is an important coenzyme that acts as
Citric acid cycle - Misplaced Pages Continue
5440-444: Is another way to identify a synthesis reaction. One example of a synthesis reaction is the combination of iron and sulfur to form iron(II) sulfide : 8 Fe + S 8 ⟶ 8 FeS {\displaystyle {\ce {8Fe + S8->8FeS}}} Another example is simple hydrogen gas combined with simple oxygen gas to produce a more complex substance, such as water. A decomposition reaction
5610-429: Is branded as a "cycle", it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized. The name of this metabolic pathway is derived from the citric acid (a tricarboxylic acid , often called citrate, as the ionized form predominates at biological pH) that is consumed and then regenerated by this sequence of reactions to complete
5780-446: Is called gluconeogenesis . Gluconeogenesis converts pyruvate to glucose-6-phosphate through a series of intermediates, many of which are shared with glycolysis . However, this pathway is not simply glycolysis run in reverse, as several steps are catalyzed by non-glycolytic enzymes. This is important as it allows the formation and breakdown of glucose to be regulated separately, and prevents both pathways from running simultaneously in
5950-409: Is captured by plants , cyanobacteria , purple bacteria , green sulfur bacteria and some protists . This process is often coupled to the conversion of carbon dioxide into organic compounds, as part of photosynthesis, which is discussed below. The energy capture and carbon fixation systems can, however, operate separately in prokaryotes, as purple bacteria and green sulfur bacteria can use sunlight as
6120-405: Is carried out by a particular coenzyme, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. These coenzymes are therefore continuously made, consumed and then recycled. One central coenzyme is adenosine triphosphate (ATP), the energy currency of cells. This nucleotide is used to transfer chemical energy between different chemical reactions. There
6290-645: Is carried out by the enzyme RuBisCO as part of the Calvin–Benson cycle . Three types of photosynthesis occur in plants, C3 carbon fixation , C4 carbon fixation and CAM photosynthesis . These differ by the route that carbon dioxide takes to the Calvin cycle, with C3 plants fixing CO 2 directly, while C4 and CAM photosynthesis incorporate the CO 2 into other compounds first, as adaptations to deal with intense sunlight and dry conditions. In photosynthetic prokaryotes
6460-627: Is catalyzed in eukaryotes by the NAD-dependent EC 1.1.1.41 , while prokaryotes employ the NADP-dependent EC 1.1.1.42 . Similarly, the conversion of ( S )-malate to oxaloacetate is catalyzed in eukaryotes by the NAD-dependent EC 1.1.1.37 , while most prokaryotes utilize a quinone-dependent enzyme, EC 1.1.5.4 . A step with significant variability is the conversion of succinyl-CoA to succinate. Most organisms utilize EC 6.2.1.5 , succinate–CoA ligase (ADP-forming) (despite its name,
6630-485: Is composed of a phosphate attached to a ribose or deoxyribose sugar group which is attached to a nitrogenous base . Nucleic acids are critical for the storage and use of genetic information, and its interpretation through the processes of transcription and protein biosynthesis . This information is protected by DNA repair mechanisms and propagated through DNA replication . Many viruses have an RNA genome , such as HIV , which uses reverse transcription to create
6800-559: Is endothermic at low temperatures, becoming less so with increasing temperature. Δ H ° is zero at 1855 K , and the reaction becomes exothermic above that temperature. Changes in temperature can also reverse the direction tendency of a reaction. For example, the water gas shift reaction is favored by low temperatures, but its reverse is favored by high temperatures. The shift in reaction direction tendency occurs at 1100 K . Reactions can also be characterized by their internal energy change, which takes into account changes in
6970-409: Is hydrated to malate. Lastly, beta-hydroxyacyl-CoA is oxidized to beta-ketoacyl-CoA while NAD+ is reduced to NADH, which follows the same process as the oxidation of malate to oxaloacetate . In the liver, the carboxylation of cytosolic pyruvate into intra-mitochondrial oxaloacetate is an early step in the gluconeogenic pathway which converts lactate and de-aminated alanine into glucose, under
Citric acid cycle - Misplaced Pages Continue
7140-477: Is its primary structure . Just as the letters of the alphabet can be combined to form an almost endless variety of words, amino acids can be linked in varying sequences to form a huge variety of proteins. Proteins are made from amino acids that have been activated by attachment to a transfer RNA molecule through an ester bond. This aminoacyl-tRNA precursor is produced in an ATP -dependent reaction carried out by an aminoacyl tRNA synthetase . This aminoacyl-tRNA
7310-635: Is likely due to their efficacy . In various diseases, such as type II diabetes , metabolic syndrome , and cancer , normal metabolism is disrupted. The metabolism of cancer cells is also different from the metabolism of normal cells, and these differences can be used to find targets for therapeutic intervention in cancer. Most of the structures that make up animals, plants and microbes are made from four basic classes of molecules : amino acids , carbohydrates , nucleic acid and lipids (often called fats ). As these molecules are vital for life, metabolic reactions either focus on making these molecules during
7480-462: Is more thermal energy available to reach the activation energy necessary for breaking bonds between atoms. A reaction may be classified as redox in which oxidation and reduction occur or non-redox in which there is no oxidation and reduction occurring. Most simple redox reactions may be classified as a combination, decomposition, or single displacement reaction. Different chemical reactions are used during chemical synthesis in order to obtain
7650-448: Is necessary to promote degradation of the latter (as under conditions of low oxygen there will not be adequate substrate for hydroxylation). This results in a pseudohypoxic phenotype in the cancer cell that promotes angiogenesis , metabolic reprogramming, cell growth , and migration . Allosteric regulation by metabolites . The regulation of the citric acid cycle is largely determined by product inhibition and substrate availability. If
7820-563: Is needed, or back to glucose in the Cori cycle . An alternative route for glucose breakdown is the pentose phosphate pathway , which produces less energy but supports anabolism (biomolecule synthesis). This pathway reduces the coenzyme NADP to NADPH and produces pentose compounds such as ribose 5-phosphate for synthesis of many biomolecules such as nucleotides and aromatic amino acids . Fats are catabolized by hydrolysis to free fatty acids and glycerol. The glycerol enters glycolysis and
7990-411: Is no known allosteric mechanism that can account for large changes in reaction rate from an allosteric effector whose concentration changes less than 10%. Citrate is used for feedback inhibition, as it inhibits phosphofructokinase , an enzyme involved in glycolysis that catalyses formation of fructose 1,6-bisphosphate , a precursor of pyruvate. This prevents a constant high rate of flux when there
8160-478: Is only a small amount of ATP in cells, but as it is continuously regenerated, the human body can use about its own weight in ATP per day. ATP acts as a bridge between catabolism and anabolism . Catabolism breaks down molecules, and anabolism puts them together. Catabolic reactions generate ATP, and anabolic reactions consume it. It also serves as a carrier of phosphate groups in phosphorylation reactions. A vitamin
8330-411: Is produced in response to rises in blood glucose levels . Binding of the hormone to insulin receptors on cells then activates a cascade of protein kinases that cause the cells to take up glucose and convert it into storage molecules such as fatty acids and glycogen . The metabolism of glycogen is controlled by activity of phosphorylase , the enzyme that breaks down glycogen, and glycogen synthase ,
8500-427: Is released. Typical examples of exothermic reactions are combustion , precipitation and crystallization , in which ordered solids are formed from disordered gaseous or liquid phases. In contrast, in endothermic reactions, heat is consumed from the environment. This can occur by increasing the entropy of the system, often through the formation of gaseous or dissolved reaction products, which have higher entropy. Since
8670-546: Is scarce, or when cells undergo metabolic stress. Lipids are the most diverse group of biochemicals. Their main structural uses are as part of internal and external biological membranes , such as the cell membrane . Their chemical energy can also be used. Lipids contain a long, non-polar hydrocarbon chain with a small polar region containing oxygen. Lipids are usually defined as hydrophobic or amphipathic biological molecules but will dissolve in organic solvents such as ethanol , benzene or chloroform . The fats are
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#17327826538978840-457: Is synthesized constitutively, and hydroxylation of at least one of two critical proline residues mediates their interaction with the von Hippel Lindau E3 ubiquitin ligase complex, which targets them for rapid degradation. This reaction is catalysed by prolyl 4-hydroxylases . Fumarate and succinate have been identified as potent inhibitors of prolyl hydroxylases, thus leading to the stabilisation of HIF. Several catabolic pathways converge on
9010-537: Is that only a portion of one molecule is transferred to the other molecule. This type of reaction occurs, for example, in redox and acid-base reactions. In redox reactions, the transferred particle is an electron, whereas in acid-base reactions it is a proton. This type of reaction is also called metathesis . for example Most chemical reactions are reversible; that is, they can and do run in both directions. The forward and reverse reactions are competing with each other and differ in reaction rates . These rates depend on
9180-617: Is the measure of the amount of energy consumed by all of these chemical reactions. A striking feature of metabolism is the similarity of the basic metabolic pathways among vastly different species. For example, the set of carboxylic acids that are best known as the intermediates in the citric acid cycle are present in all known organisms, being found in species as diverse as the unicellular bacterium Escherichia coli and huge multicellular organisms like elephants . These similarities in metabolic pathways are likely due to their early appearance in evolutionary history , and their retention
9350-529: Is the set of life -sustaining chemical reactions in organisms . The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks of proteins , lipids , nucleic acids , and some carbohydrates ; and the elimination of metabolic wastes . These enzyme -catalyzed reactions allow organisms to grow and reproduce, maintain their structures , and respond to their environments. The word metabolism can also refer to
9520-430: Is the starting point for the citric acid cycle. Acetyl-CoA may also be obtained from the oxidation of fatty acids . Below is a schematic outline of the cycle: There are ten basic steps in the citric acid cycle, as outlined below. The cycle is continuously supplied with new carbon in the form of acetyl-CoA , entering at step 0 in the table. Two carbon atoms are oxidized to CO 2 , the energy from these reactions
9690-422: Is the synthesis of carbohydrates from sunlight and carbon dioxide (CO 2 ). In plants, cyanobacteria and algae, oxygenic photosynthesis splits water, with oxygen produced as a waste product. This process uses the ATP and NADPH produced by the photosynthetic reaction centres , as described above, to convert CO 2 into glycerate 3-phosphate , which can then be converted into glucose. This carbon-fixation reaction
9860-536: Is then decarboxylated to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase , which is the rate limiting step in the conversion of nearly all the gluconeogenic precursors (such as the glucogenic amino acids and lactate) into glucose by the liver and kidney . Because the citric acid cycle is involved in both catabolic and anabolic processes, it is known as an amphibolic pathway. Evan M.W.Duo Click on genes, proteins and metabolites below to link to respective articles. The metabolic role of lactate
10030-495: Is then a substrate for the ribosome , which joins the amino acid onto the elongating protein chain, using the sequence information in a messenger RNA . Nucleotides are made from amino acids, carbon dioxide and formic acid in pathways that require large amounts of metabolic energy. Consequently, most organisms have efficient systems to salvage preformed nucleotides. Purines are synthesized as nucleosides (bases attached to ribose ). Both adenine and guanine are made from
10200-455: Is transferred to other metabolic processes through GTP (or ATP), and as electrons in NADH and QH 2 . The NADH generated in the citric acid cycle may later be oxidized (donate its electrons) to drive ATP synthesis in a type of process called oxidative phosphorylation . FADH 2 is covalently attached to succinate dehydrogenase , an enzyme which functions both in the citric acid cycle and
10370-423: Is transformed through a series of steps into another chemical, each step being facilitated by a specific enzyme . Enzymes are crucial to metabolism because they allow organisms to drive desirable reactions that require energy and will not occur by themselves, by coupling them to spontaneous reactions that release energy. Enzymes act as catalysts —they allow a reaction to proceed more rapidly—and they also allow
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#173278265389710540-450: Is used by organisms that respire (as opposed to organisms that ferment ) to generate energy, either by anaerobic respiration or aerobic respiration . In addition, the cycle provides precursors of certain amino acids , as well as the reducing agent NADH , that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism . Even though it
10710-429: Is used in anabolic reactions. Inorganic elements play critical roles in metabolism; some are abundant (e.g. sodium and potassium ) while others function at minute concentrations. About 99% of a human's body weight is made up of the elements carbon , nitrogen , calcium , sodium , chlorine , potassium , hydrogen , phosphorus , oxygen and sulfur . Organic compounds (proteins, lipids and carbohydrates) contain
10880-413: Is used in retro reactions. The elementary reaction is the smallest division into which a chemical reaction can be decomposed, it has no intermediate products. Most experimentally observed reactions are built up from many elementary reactions that occur in parallel or sequentially. The actual sequence of the individual elementary reactions is known as reaction mechanism . An elementary reaction involves
11050-505: Is well recognized as a fuel for tissues , mitochondrial cytopathies such as DPH Cytopathy, and the scientific field of oncology ( tumors ). In the classical Cori cycle , muscles produce lactate which is then taken up by the liver for gluconeogenesis . New studies suggest that lactate can be used as a source of carbon for the TCA cycle. It is believed that components of the citric acid cycle were derived from anaerobic bacteria , and that
11220-532: Is when a more complex substance breaks down into its more simple parts. It is thus the opposite of a synthesis reaction and can be written as AB ⟶ A + B {\displaystyle {\ce {AB->A + B}}} One example of a decomposition reaction is the electrolysis of water to make oxygen and hydrogen gas: 2 H 2 O ⟶ 2 H 2 + O 2 {\displaystyle {\ce {2H2O->2H2 + O2}}} In
11390-549: The Four-Element Theory of Empedocles stating that any substance is composed of the four basic elements – fire, water, air and earth. In the Middle Ages , chemical transformations were studied by alchemists . They attempted, in particular, to convert lead into gold , for which purpose they used reactions of lead and lead-copper alloys with sulfur . The artificial production of chemical substances already
11560-1417: The Gibbs free energy of the reaction. They require input of energy to proceed in the forward direction. Examples include: In a combustion reaction, an element or compound reacts with an oxidant, usually oxygen , often producing energy in the form of heat or light . Combustion reactions frequently involve a hydrocarbon . For instance, the combustion of 1 mole (114 g) of octane in oxygen C 8 H 18 ( l ) + 25 2 O 2 ( g ) ⟶ 8 CO 2 + 9 H 2 O ( l ) {\displaystyle {\ce {C8H18(l) + 25/2 O2(g)->8CO2 + 9H2O(l)}}} releases 5500 kJ. A combustion reaction can also result from carbon , magnesium or sulfur reacting with oxygen. 2 Mg ( s ) + O 2 ⟶ 2 MgO ( s ) {\displaystyle {\ce {2Mg(s) + O2->2MgO(s)}}} S ( s ) + O 2 ( g ) ⟶ SO 2 ( g ) {\displaystyle {\ce {S(s) + O2(g)->SO2(g)}}} Metabolism Metabolism ( / m ə ˈ t æ b ə l ɪ z ə m / , from Greek : μεταβολή metabolē , "change")
11730-497: The Le Chatelier's principle . For example, an increase in pressure due to decreasing volume causes the reaction to shift to the side with fewer moles of gas. The reaction yield stabilizes at equilibrium but can be increased by removing the product from the reaction mixture or changed by increasing the temperature or pressure. A change in the concentrations of the reactants does not affect the equilibrium constant but does affect
11900-532: The University of Sheffield , for which the former received the Nobel Prize for Physiology or Medicine in 1953, and for whom the cycle is sometimes named the "Krebs cycle". The citric acid cycle is a metabolic pathway that connects carbohydrate , fat , and protein metabolism . The reactions of the cycle are carried out by eight enzymes that completely oxidize acetate (a two carbon molecule), in
12070-667: The alpha keto-acids formed from the citric acid cycle intermediates have to acquire their amino groups from glutamate in a transamination reaction, in which pyridoxal phosphate is a cofactor. In this reaction the glutamate is converted into alpha-ketoglutarate , which is a citric acid cycle intermediate. The intermediates that can provide the carbon skeletons for amino acid synthesis are oxaloacetate which forms aspartate and asparagine ; and alpha-ketoglutarate which forms glutamine , proline , and arginine . Of these amino acids, aspartate and glutamine are used, together with carbon and nitrogen atoms from other sources, to form
12240-426: The bioremediation of contaminated land and oil spills. Many of these microbial reactions are shared with multicellular organisms, but due to the incredible diversity of types of microbes these organisms are able to deal with a far wider range of xenobiotics than multicellular organisms, and can degrade even persistent organic pollutants such as organochloride compounds. A related problem for aerobic organisms
12410-503: The chloroplast . These protons move back through the membrane as they drive the ATP synthase, as before. The electrons then flow through photosystem I and can then be used to reduce the coenzyme NADP . This coenzyme can enter the Calvin cycle or be recycled for further ATP generation. Anabolism is the set of constructive metabolic processes where the energy released by catabolism is used to synthesize complex molecules. In general,
12580-458: The contact process in the 1880s, and the Haber process was developed in 1909–1910 for ammonia synthesis. From the 16th century, researchers including Jan Baptist van Helmont , Robert Boyle , and Isaac Newton tried to establish theories of experimentally observed chemical transformations. The phlogiston theory was proposed in 1667 by Johann Joachim Becher . It postulated the existence of
12750-467: The control exerted by this enzyme is the effect that these changes in its activity have on the overall rate of the pathway (the flux through the pathway). For example, an enzyme may show large changes in activity (i.e. it is highly regulated) but if these changes have little effect on the flux of a metabolic pathway, then this enzyme is not involved in the control of the pathway. There are multiple levels of metabolic regulation. In intrinsic regulation,
12920-441: The cytoskeleton , a system of scaffolding that maintains the cell shape. Proteins are also important in cell signaling , immune responses , cell adhesion , active transport across membranes, and the cell cycle . Amino acids also contribute to cellular energy metabolism by providing a carbon source for entry into the citric acid cycle ( tricarboxylic acid cycle ), especially when a primary source of energy, such as glucose ,
13090-406: The last universal common ancestor . This universal ancestral cell was prokaryotic and probably a methanogen that had extensive amino acid, nucleotide, carbohydrate and lipid metabolism. The retention of these ancient pathways during later evolution may be the result of these reactions having been an optimal solution to their particular metabolic problems, with pathways such as glycolysis and
13260-550: The mevalonate pathway produces these compounds from acetyl-CoA, while in plants and bacteria the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates. One important reaction that uses these activated isoprene donors is sterol biosynthesis . Here, the isoprene units are joined to make squalene and then folded up and formed into a set of rings to make lanosterol . Lanosterol can then be converted into other sterols such as cholesterol and ergosterol . Organisms vary in their ability to synthesize
13430-561: The oxidation of isocitrate to oxalosuccinate , which then spontaneously decarboxylates to alpha-ketoglutarate , as discussed above; in this case an additional reduction step occurs after the formation of alpha-ketoglutarate via NADPH to yield 2-hydroxyglutarate), and hence IDH is considered an oncogene . Under physiological conditions, 2-hydroxyglutarate is a minor product of several metabolic pathways as an error but readily converted to alpha-ketoglutarate via hydroxyglutarate dehydrogenase enzymes ( L2HGDH and D2HGDH ) but does not have
13600-545: The pentose phosphate pathway in the cytoplasm. The depletion of NADPH results in increased oxidative stress within the cell as it is a required cofactor in the production of GSH , and this oxidative stress can result in DNA damage. There are also changes on the genetic and epigenetic level through the function of histone lysine demethylases (KDMs) and ten-eleven translocation (TET) enzymes; ordinarily TETs hydroxylate 5-methylcytosines to prime them for demethylation. However, in
13770-496: The purines that are used as the bases in DNA and RNA , as well as in ATP , AMP , GTP , NAD , FAD and CoA . The pyrimidines are partly assembled from aspartate (derived from oxaloacetate ). The pyrimidines, thymine , cytosine and uracil , form the complementary bases to the purine bases in DNA and RNA, and are also components of CTP , UMP , UDP and UTP . The majority of
13940-426: The regulation of the rate of a metabolic reaction, for example in response to changes in the cell's environment or to signals from other cells. The metabolic system of a particular organism determines which substances it will find nutritious and which poisonous . For example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals. The basal metabolic rate of an organism
14110-471: The stoichiometry , the number of atoms of each species should be the same on both sides of the equation. This is achieved by scaling the number of involved molecules (A, B, C and D in a schematic example below) by the appropriate integers a, b, c and d . More elaborate reactions are represented by reaction schemes, which in addition to starting materials and products show important intermediates or transition states . Also, some relatively minor additions to
14280-407: The stomach and pancreas , and in salivary glands . The amino acids or sugars released by these extracellular enzymes are then pumped into cells by active transport proteins. Carbohydrate catabolism is the breakdown of carbohydrates into smaller units. Carbohydrates are usually taken into cells after they have been digested into monosaccharides such as glucose and fructose . Once inside,
14450-562: The transition state theory , the calculation of the potential energy surface , the Marcus theory and the Rice–Ramsperger–Kassel–Marcus (RRKM) theory . In a synthesis reaction, two or more simple substances combine to form a more complex substance. These reactions are in the general form: A + B ⟶ AB {\displaystyle {\ce {A + B->AB}}} Two or more reactants yielding one product
14620-486: The 17th century, Johann Rudolph Glauber produced hydrochloric acid and sodium sulfate by reacting sulfuric acid and sodium chloride . With the development of the lead chamber process in 1746 and the Leblanc process , allowing large-scale production of sulfuric acid and sodium carbonate , respectively, chemical reactions became implemented into the industry. Further optimization of sulfuric acid technology resulted in
14790-428: The 20 common amino acids. Most bacteria and plants can synthesize all twenty, but mammals can only synthesize eleven nonessential amino acids, so nine essential amino acids must be obtained from food. Some simple parasites , such as the bacteria Mycoplasma pneumoniae , lack all amino acid synthesis and take their amino acids directly from their hosts. All amino acids are synthesized from intermediates in glycolysis,
14960-555: The 2Cl anion, giving the compounds BaSO 4 and MgCl 2 . Another example of a double displacement reaction is the reaction of lead(II) nitrate with potassium iodide to form lead(II) iodide and potassium nitrate : Pb ( NO 3 ) 2 + 2 KI ⟶ PbI 2 ↓ + 2 KNO 3 {\displaystyle {\ce {Pb(NO3)2 + 2KI->PbI2(v) + 2KNO3}}} According to Le Chatelier's Principle , reactions may proceed in
15130-476: The ADP and GDP ions, respectively, and ATP and GTP the ATP and GTP ions, respectively. The total number of ATP molecules obtained after complete oxidation of one glucose in glycolysis, citric acid cycle, and oxidative phosphorylation is estimated to be between 30 and 38. The theoretical maximum yield of ATP through oxidation of one molecule of glucose in glycolysis, citric acid cycle, and oxidative phosphorylation
15300-404: The TCA cycle itself may have evolved more than once. It may even predate biosis: the substrates appear to undergo most of the reactions spontaneously in the presence of persulfate radicals. Theoretically, several alternatives to the TCA cycle exist; however, the TCA cycle appears to be the most efficient. If several TCA alternatives had evolved independently, they all appear to have converged to
15470-433: The TCA cycle with acetate metabolism in these organisms. Some bacteria, such as Helicobacter pylori , employ yet another enzyme for this conversion – succinyl-CoA:acetoacetate CoA-transferase ( EC 2.8.3.5 ). Some variability also exists at the previous step – the conversion of 2-oxoglutarate to succinyl-CoA. While most organisms utilize the ubiquitous NAD-dependent 2-oxoglutarate dehydrogenase, some bacteria utilize
15640-419: The TCA cycle. Acetyl-CoA Oxaloacetate Chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an energy change as new products are generated. Classically, chemical reactions encompass changes that only involve
15810-411: The TCA intermediates are identified by italics . Several of the citric acid cycle intermediates are used for the synthesis of important compounds, which will have significant cataplerotic effects on the cycle. Acetyl-CoA cannot be transported out of the mitochondrion. To obtain cytosolic acetyl-CoA, citrate is removed from the citric acid cycle and carried across the inner mitochondrial membrane into
15980-560: The absence of alpha-ketoglutarate this cannot be done and there is hence hypermethylation of the cell's DNA, serving to promote epithelial-mesenchymal transition (EMT) and inhibit cellular differentiation. A similar phenomenon is observed for the Jumonji C family of KDMs which require a hydroxylation to perform demethylation at the epsilon-amino methyl group. Additionally, the inability of prolyl hydroxylases to catalyze reactions results in stabilization of hypoxia-inducible factor alpha , which
16150-408: The atomic theory of John Dalton , Joseph Proust had developed the law of definite proportions , which later resulted in the concepts of stoichiometry and chemical equations . Regarding the organic chemistry , it was long believed that compounds obtained from living organisms were too complex to be obtained synthetically . According to the concept of vitalism , organic matter was endowed with
16320-468: The availability of ATP to the cell. Acetyl-CoA , on the other hand, derived from pyruvate oxidation, or from the beta-oxidation of fatty acids , is the only fuel to enter the citric acid cycle. With each turn of the cycle one molecule of acetyl-CoA is consumed for every molecule of oxaloacetate present in the mitochondrial matrix, and is never regenerated. It is the oxidation of the acetate portion of acetyl-CoA that produces CO 2 and water, with
16490-431: The brain that cannot metabolize fatty acids. In other organisms such as plants and bacteria, this metabolic problem is solved using the glyoxylate cycle , which bypasses the decarboxylation step in the citric acid cycle and allows the transformation of acetyl-CoA to oxaloacetate , where it can be used for the production of glucose. Other than fat, glucose is stored in most tissues, as an energy resource available within
16660-433: The carbon atoms in the porphyrins come from the citric acid cycle intermediate, succinyl-CoA . These molecules are an important component of the hemoproteins , such as hemoglobin , myoglobin and various cytochromes . During gluconeogenesis mitochondrial oxaloacetate is reduced to malate which is then transported out of the mitochondrion, to be oxidized back to oxaloacetate in the cytosol. Cytosolic oxaloacetate
16830-439: The cell for energy. M. tuberculosis can also grow on the lipid cholesterol as a sole source of carbon, and genes involved in the cholesterol-use pathway(s) have been validated as important during various stages of the infection lifecycle of M. tuberculosis . Amino acids are either used to synthesize proteins and other biomolecules, or oxidized to urea and carbon dioxide to produce energy. The oxidation pathway starts with
17000-413: The citric acid cycle all the intermediates (e.g. citrate , iso-citrate , alpha-ketoglutarate , succinate , fumarate , malate , and oxaloacetate ) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that that additional amount is retained within the cycle, increasing all the other intermediates as one is converted into
17170-407: The citric acid cycle are, in turn, used by the oxidative phosphorylation pathway to generate energy-rich ATP. One of the primary sources of acetyl-CoA is from the breakdown of sugars by glycolysis which yield pyruvate that in turn is decarboxylated by the pyruvate dehydrogenase complex generating acetyl-CoA according to the following reaction scheme: The product of this reaction, acetyl-CoA,
17340-408: The citric acid cycle occurs in the matrix of the mitochondrion . In prokaryotic cells, such as bacteria, which lack mitochondria, the citric acid cycle reaction sequence is performed in the cytosol with the proton gradient for ATP production being across the cell's surface ( plasma membrane ) rather than the inner membrane of the mitochondrion . For each pyruvate molecule (from glycolysis ),
17510-441: The citric acid cycle producing their end products highly efficiently and in a minimal number of steps. The first pathways of enzyme-based metabolism may have been parts of purine nucleotide metabolism, while previous metabolic pathways were a part of the ancient RNA world . Many models have been proposed to describe the mechanisms by which novel metabolic pathways evolve. These include the sequential addition of novel enzymes to
17680-416: The citric acid cycle, or the pentose phosphate pathway. Nitrogen is provided by glutamate and glutamine . Nonessensial amino acid synthesis depends on the formation of the appropriate alpha-keto acid, which is then transaminated to form an amino acid. Amino acids are made into proteins by being joined in a chain of peptide bonds . Each different protein has a unique sequence of amino acid residues: this
17850-454: The citric acid cycle. Most of these reactions add intermediates to the citric acid cycle, and are therefore known as anaplerotic reactions , from the Greek meaning to "fill up". These increase the amount of acetyl CoA that the cycle is able to carry, increasing the mitochondrion's capability to carry out respiration if this is otherwise a limiting factor. Processes that remove intermediates from
18020-637: The coenzyme nicotinamide adenine dinucleotide (NAD ) into NADH. Macromolecules cannot be directly processed by cells. Macromolecules must be broken into smaller units before they can be used in cell metabolism. Different classes of enzymes are used to digest these polymers. These digestive enzymes include proteases that digest proteins into amino acids, as well as glycoside hydrolases that digest polysaccharides into simple sugars known as monosaccharides . Microbes simply secrete digestive enzymes into their surroundings, while animals only secrete these enzymes from specialized cells in their guts , including
18190-534: The complex molecules that make up cellular structures are constructed step-by-step from smaller and simpler precursors. Anabolism involves three basic stages. First, the production of precursors such as amino acids , monosaccharides , isoprenoids and nucleotides , secondly, their activation into reactive forms using energy from ATP, and thirdly, the assembly of these precursors into complex molecules such as proteins , polysaccharides , lipids and nucleic acids . Anabolism in organisms can be different according to
18360-481: The concentration and therefore change with the time of the reaction: the reverse rate gradually increases and becomes equal to the rate of the forward reaction, establishing the so-called chemical equilibrium. The time to reach equilibrium depends on parameters such as temperature, pressure, and the materials involved, and is determined by the minimum free energy . In equilibrium, the Gibbs free energy of reaction must be zero. The pressure dependence can be explained with
18530-488: The construction of cells and tissues, or on breaking them down and using them to obtain energy, by their digestion. These biochemicals can be joined to make polymers such as DNA and proteins , essential macromolecules of life. Proteins are made of amino acids arranged in a linear chain joined by peptide bonds . Many proteins are enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as those that form
18700-408: The cycle are one GTP (or ATP ), three NADH , one FADH 2 and two CO 2 . Because two acetyl-CoA molecules are produced from each glucose molecule, two cycles are required per glucose molecule. Therefore, at the end of two cycles, the products are: two GTP, six NADH, two FADH 2 , and four CO 2 . The above reactions are balanced if P i represents the H 2 PO 4 ion, ADP and GDP
18870-453: The cycle are termed "cataplerotic" reactions. In this section and in the next, the citric acid cycle intermediates are indicated in italics to distinguish them from other substrates and end-products. Pyruvate molecules produced by glycolysis are actively transported across the inner mitochondrial membrane, and into the matrix. Here they can be oxidized and combined with coenzyme A to form CO 2 , acetyl-CoA , and NADH , as in
19040-409: The cycle were permitted to run unchecked, large amounts of metabolic energy could be wasted in overproduction of reduced coenzyme such as NADH and ATP. The major eventual substrate of the cycle is ADP which gets converted to ATP. A reduced amount of ADP causes accumulation of precursor NADH which in turn can inhibit a number of enzymes. NADH, a product of all dehydrogenases in the citric acid cycle with
19210-468: The cycle. He made this discovery by studying pigeon breast muscle. Because this tissue maintains its oxidative capacity well after breaking down in the Latapie mincer and releasing in aqueous solutions, breast muscle of the pigeon was very well qualified for the study of oxidative reactions. The citric acid cycle itself was finally identified in 1937 by Hans Adolf Krebs and William Arthur Johnson while at
19380-406: The cycle. The cycle consumes acetate (in the form of acetyl-CoA) and water , reduces NAD to NADH, releasing carbon dioxide. The NADH generated by the citric acid cycle is fed into the oxidative phosphorylation (electron transport) pathway. The net result of these two closely linked pathways is the oxidation of nutrients to produce usable chemical energy in the form of ATP. In eukaryotic cells,
19550-587: The cytosol. There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to mitochondrion as malate (and then converted back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion). The cytosolic acetyl-CoA is used for fatty acid synthesis and the production of cholesterol . Cholesterol can, in turn, be used to synthesize the steroid hormones , bile salts , and vitamin D . The carbon skeletons of many non-essential amino acids are made from citric acid cycle intermediates. To turn them into amino acids
19720-457: The de-aminated amino acids) may either enter the citric acid cycle as intermediates (e.g. alpha-ketoglutarate derived from glutamate or glutamine), having an anaplerotic effect on the cycle, or, in the case of leucine , isoleucine , lysine , phenylalanine , tryptophan , and tyrosine , they are converted into acetyl-CoA which can be burned to CO 2 and water, or used to form ketone bodies , which too can only be burned in tissues other than
19890-444: The desired product. In biochemistry , a consecutive series of chemical reactions (where the product of one reaction is the reactant of the next reaction) form metabolic pathways . These reactions are often catalyzed by protein enzymes . Enzymes increase the rates of biochemical reactions, so that metabolic syntheses and decompositions impossible under ordinary conditions can occur at the temperature and concentrations present within
20060-445: The electrons removed from organic molecules in areas such as the citric acid cycle are transferred to oxygen and the energy released is used to make ATP. This is done in eukaryotes by a series of proteins in the membranes of mitochondria called the electron transport chain . In prokaryotes , these proteins are found in the cell's inner membrane . These proteins use the energy from reduced molecules like NADH to pump protons across
20230-683: The end of the reaction catalyzed. Metal micronutrients are taken up into organisms by specific transporters and bind to storage proteins such as ferritin or metallothionein when not in use. Catabolism is the set of metabolic processes that break down large molecules. These include breaking down and oxidizing food molecules. The purpose of the catabolic reactions is to provide the energy and components needed by anabolic reactions which build molecules. The exact nature of these catabolic reactions differ from organism to organism, and organisms can be classified based on their sources of energy, hydrogen, and carbon (their primary nutritional groups ), as shown in
20400-427: The energy thus released captured in the form of ATP. The three steps of beta-oxidation resemble the steps that occur in the production of oxaloacetate from succinate in the TCA cycle. Acyl-CoA is oxidized to trans-Enoyl-CoA while FAD is reduced to FADH 2 , which is similar to the oxidation of succinate to fumarate. Following, trans-enoyl-CoA is hydrated across the double bond to beta-hydroxyacyl-CoA, just like fumarate
20570-455: The entropy term in the free-energy change increases with temperature, many endothermic reactions preferably take place at high temperatures. On the contrary, many exothermic reactions such as crystallization occur preferably at lower temperatures. A change in temperature can sometimes reverse the sign of the enthalpy of a reaction, as for the carbon monoxide reduction of molybdenum dioxide : This reaction to form carbon dioxide and molybdenum
20740-405: The entropy, volume and chemical potentials . The latter depends, among other things, on the activities of the involved substances. The speed at which reactions take place is studied by reaction kinetics . The rate depends on various parameters, such as: Several theories allow calculating the reaction rates at the molecular level. This field is referred to as reaction dynamics. The rate v of
20910-440: The enzyme operates in the pathway in the direction of ATP formation). In mammals a GTP-forming enzyme, succinate–CoA ligase (GDP-forming) ( EC 6.2.1.4 ) also operates. The level of utilization of each isoform is tissue dependent. In some acetate-producing bacteria, such as Acetobacter aceti , an entirely different enzyme catalyzes this conversion – EC 2.8.3.18 , succinyl-CoA:acetate CoA-transferase. This specialized enzyme links
21080-469: The enzyme that makes it. These enzymes are regulated in a reciprocal fashion, with phosphorylation inhibiting glycogen synthase, but activating phosphorylase. Insulin causes glycogen synthesis by activating protein phosphatases and producing a decrease in the phosphorylation of these enzymes. The central pathways of metabolism described above, such as glycolysis and the citric acid cycle, are present in all three domains of living things and were present in
21250-406: The equilibrium position. Chemical reactions are determined by the laws of thermodynamics . Reactions can proceed by themselves if they are exergonic , that is if they release free energy. The associated free energy change of the reaction is composed of the changes of two different thermodynamic quantities, enthalpy and entropy : Reactions can be exothermic , where Δ H is negative and energy
21420-512: The exception of succinate dehydrogenase , inhibits pyruvate dehydrogenase , isocitrate dehydrogenase , α-ketoglutarate dehydrogenase , and also citrate synthase . Acetyl-coA inhibits pyruvate dehydrogenase , while succinyl-CoA inhibits alpha-ketoglutarate dehydrogenase and citrate synthase . When tested in vitro with TCA enzymes, ATP inhibits citrate synthase and α-ketoglutarate dehydrogenase ; however, ATP levels do not change more than 10% in vivo between rest and vigorous exercise. There
21590-650: The exchange of electrolytes between the extracellular fluid and the cell's fluid, the cytosol . Electrolytes enter and leave cells through proteins in the cell membrane called ion channels . For example, muscle contraction depends upon the movement of calcium, sodium and potassium through ion channels in the cell membrane and T-tubules . Transition metals are usually present as trace elements in organisms, with zinc and iron being most abundant of those. Metal cofactors are bound tightly to specific sites in proteins; although enzyme cofactors can be modified during catalysis, they always return to their original state by
21760-414: The fatty acids are broken down by beta oxidation to release acetyl-CoA, which then is fed into the citric acid cycle. Fatty acids release more energy upon oxidation than carbohydrates. Steroids are also broken down by some bacteria in a process similar to beta oxidation, and this breakdown process involves the release of significant amounts of acetyl-CoA, propionyl-CoA, and pyruvate, which can all be used by
21930-484: The first stage, large organic molecules, such as proteins , polysaccharides or lipids , are digested into their smaller components outside cells. Next, these smaller molecules are taken up by cells and converted to smaller molecules, usually acetyl coenzyme A (acetyl-CoA), which releases some energy. Finally, the acetyl group on acetyl-CoA is oxidized to water and carbon dioxide in the citric acid cycle and electron transport chain , releasing more energy while reducing
22100-642: The form of acetyl-CoA, into two molecules each of carbon dioxide and water. Through catabolism of sugars, fats, and proteins, the two-carbon organic product acetyl-CoA is produced which enters the citric acid cycle. The reactions of the cycle also convert three equivalents of nicotinamide adenine dinucleotide (NAD) into three equivalents of reduced NAD (NADH), one equivalent of flavin adenine dinucleotide (FAD) into one equivalent of FADH 2 , and one equivalent each of guanosine diphosphate (GDP) and inorganic phosphate (P i ) into one equivalent of guanosine triphosphate (GTP). The NADH and FADH 2 generated by
22270-448: The form of heat or light. A typical example of a unimolecular reaction is the cis–trans isomerization , in which the cis-form of a compound converts to the trans-form or vice versa. In a typical dissociation reaction, a bond in a molecule splits ( ruptures ) resulting in two molecular fragments. The splitting can be homolytic or heterolytic . In the first case, the bond is divided so that each product retains an electron and becomes
22440-405: The form of water-soluble messengers such as hormones and growth factors and are detected by specific receptors on the cell surface. These signals are then transmitted inside the cell by second messenger systems that often involved the phosphorylation of proteins. A very well understood example of extrinsic control is the regulation of glucose metabolism by the hormone insulin . Insulin
22610-401: The formation of 2 acetyl-CoA molecules, their catabolism in the citric acid cycle, and oxidative phosphorylation equals about 30 ATP molecules , in eukaryotes . The number of ATP molecules derived from the beta oxidation of a 6 carbon segment of a fatty acid chain, and the subsequent oxidation of the resulting 3 molecules of acetyl-CoA is 40. In this subheading, as in the previous one,
22780-407: The forward or reverse direction until they end or reach equilibrium . Reactions that proceed in the forward direction (from left to right) to approach equilibrium are often called spontaneous reactions , that is, Δ G {\displaystyle \Delta G} is negative, which means that if they occur at constant temperature and pressure, they decrease the Gibbs free energy of
22950-431: The glycerol can be converted into glucose via dihydroxyacetone phosphate and glyceraldehyde-3-phosphate by way of gluconeogenesis . In skeletal muscle, glycerol is used in glycolysis by converting glycerol into glycerol-3-phosphate , then into dihydroxyacetone phosphate (DHAP), then into glyceraldehyde-3-phosphate. In many tissues, especially heart and skeletal muscle tissue , fatty acids are broken down through
23120-553: The influence of high levels of glucagon and/or epinephrine in the blood. Here the addition of oxaloacetate to the mitochondrion does not have a net anaplerotic effect, as another citric acid cycle intermediate ( malate ) is immediately removed from the mitochondrion to be converted into cytosolic oxaloacetate, which is ultimately converted into glucose, in a process that is almost the reverse of glycolysis . In protein catabolism , proteins are broken down by proteases into their constituent amino acids. Their carbon skeletons (i.e.
23290-423: The liver where they are formed, or excreted via the urine or breath. These latter amino acids are therefore termed "ketogenic" amino acids, whereas those that enter the citric acid cycle as intermediates can only be cataplerotically removed by entering the gluconeogenic pathway via malate which is transported out of the mitochondrion to be converted into cytosolic oxaloacetate and ultimately into glucose . These are
23460-529: The major route of breakdown is glycolysis , in which glucose is converted into pyruvate . This process generates the energy-conveying molecule NADH from NAD , and generates ATP from ADP for use in powering many processes within the cell. Pyruvate is an intermediate in several metabolic pathways, but the majority is converted to acetyl-CoA and fed into the citric acid cycle , which enables more ATP production by means of oxidative phosphorylation . This oxidation consumes molecular oxygen and releases water and
23630-506: The majority of the carbon and nitrogen; most of the oxygen and hydrogen is present as water. The abundant inorganic elements act as electrolytes . The most important ions are sodium , potassium , calcium , magnesium , chloride , phosphate and the organic ion bicarbonate . The maintenance of precise ion gradients across cell membranes maintains osmotic pressure and pH . Ions are also critical for nerve and muscle function, as action potentials in these tissues are produced by
23800-680: The mechanisms of carbon fixation are more diverse. Here, carbon dioxide can be fixed by the Calvin–Benson cycle, a reversed citric acid cycle, or the carboxylation of acetyl-CoA. Prokaryotic chemoautotrophs also fix CO 2 through the Calvin–Benson cycle, but use energy from inorganic compounds to drive the reaction. In carbohydrate anabolism, simple organic acids can be converted into monosaccharides such as glucose and then used to assemble polysaccharides such as starch . The generation of glucose from compounds like pyruvate , lactate , glycerol , glycerate 3-phosphate and amino acids
23970-482: The metabolic pathway self-regulates to respond to changes in the levels of substrates or products; for example, a decrease in the amount of product can increase the flux through the pathway to compensate. This type of regulation often involves allosteric regulation of the activities of multiple enzymes in the pathway. Extrinsic control involves a cell in a multicellular organism changing its metabolism in response to signals from other cells. These signals are usually in
24140-409: The metabolism of the cell. For one thing, because there is an extra NADPH-catalyzed reduction, this can contribute to depletion of cellular stores of NADPH and also reduce levels of alpha-ketoglutarate available to the cell. In particular, the depletion of NADPH is problematic because NADPH is highly compartmentalized and cannot freely diffuse between the organelles in the cell. It is produced largely via
24310-497: The mitochondrial electron transport chain in oxidative phosphorylation. FADH 2 , therefore, facilitates transfer of electrons to coenzyme Q , which is the final electron acceptor of the reaction catalyzed by the succinate:ubiquinone oxidoreductase complex, also acting as an intermediate in the electron transport chain . Mitochondria in animals, including humans, possess two succinyl-CoA synthetases: one that produces GTP from GDP, and another that produces ATP from ADP. Plants have
24480-512: The most abundant biological molecules, and fill numerous roles, such as the storage and transport of energy ( starch , glycogen ) and structural components ( cellulose in plants, chitin in animals). The basic carbohydrate units are called monosaccharides and include galactose , fructose , and most importantly glucose . Monosaccharides can be linked together to form polysaccharides in almost limitless ways. The two nucleic acids, DNA and RNA , are polymers of nucleotides . Each nucleotide
24650-420: The nature of photosynthetic pigment present, with most photosynthetic bacteria only having one type, while plants and cyanobacteria have two. In plants, algae, and cyanobacteria, photosystem II uses light energy to remove electrons from water, releasing oxygen as a waste product. The electrons then flow to the cytochrome b6f complex , which uses their energy to pump protons across the thylakoid membrane in
24820-410: The net production of ATP to 36. Furthermore, inefficiencies in oxidative phosphorylation due to leakage of protons across the mitochondrial membrane and slippage of the ATP synthase /proton pump commonly reduces the ATP yield from NADH and FADH 2 to less than the theoretical maximum yield. The observed yields are, therefore, closer to ~2.5 ATP per NADH and ~1.5 ATP per FADH 2 , further reducing
24990-411: The normal cycle. However, it is also possible for pyruvate to be carboxylated by pyruvate carboxylase to form oxaloacetate . This latter reaction "fills up" the amount of oxaloacetate in the citric acid cycle, and is therefore an anaplerotic reaction, increasing the cycle's capacity to metabolize acetyl-CoA when the tissue's energy needs (e.g. in muscle ) are suddenly increased by activity. In
25160-422: The other. Hence the addition of any one of them to the cycle has an anaplerotic effect, and its removal has a cataplerotic effect. These anaplerotic and cataplerotic reactions will, during the course of the cycle, increase or decrease the amount of oxaloacetate available to combine with acetyl-CoA to form citric acid . This in turn increases or decreases the rate of ATP production by the mitochondrion, and thus
25330-464: The overall yield of energy-containing compounds from the citric acid cycle is three NADH, one FADH 2 , and one GTP . Several of the components and reactions of the citric acid cycle were established in the 1930s by the research of Albert Szent-Györgyi , who received the Nobel Prize in Physiology or Medicine in 1937 specifically for his discoveries pertaining to fumaric acid , a component of
25500-412: The pathway. Terpenes and isoprenoids are a large class of lipids that include the carotenoids and form the largest class of plant natural products . These compounds are made by the assembly and modification of isoprene units donated from the reactive precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate . These precursors can be made in different ways. In animals and archaea,
25670-454: The positions of electrons in the forming and breaking of chemical bonds between atoms , with no change to the nuclei (no change to the elements present), and can often be described by a chemical equation . Nuclear chemistry is a sub-discipline of chemistry that involves the chemical reactions of unstable and radioactive elements where both electronic and nuclear changes can occur. The substance (or substances) initially involved in
25840-674: The precursor nucleoside inosine monophosphate, which is synthesized using atoms from the amino acids glycine , glutamine , and aspartic acid , as well as formate transferred from the coenzyme tetrahydrofolate . Pyrimidines , on the other hand, are synthesized from the base orotate , which is formed from glutamine and aspartate. All organisms are constantly exposed to compounds that they cannot use as foods and that would be harmful if they accumulated in cells, as they have no metabolic function. These potentially damaging compounds are called xenobiotics . Xenobiotics such as synthetic drugs , natural poisons and antibiotics are detoxified by
26010-400: The proliferation of tumor cells, and consequently metabolites can accumulate which serve to facilitate tumorigenesis , dubbed onco metabolites . Among the best characterized oncometabolites is 2-hydroxyglutarate which is produced through a heterozygous gain-of-function mutation (specifically a neomorphic one) in isocitrate dehydrogenase (IDH) (which under normal circumstances catalyzes
26180-404: The reactants on the left and those of the products on the right. They are separated by an arrow (→) which indicates the direction and type of the reaction; the arrow is read as the word "yields". The tip of the arrow points in the direction in which the reaction proceeds. A double arrow (⇌) pointing in opposite directions is used for equilibrium reactions . Equations should be balanced according to
26350-457: The reaction can be indicated above the reaction arrow; examples of such additions are water, heat, illumination, a catalyst , etc. Similarly, some minor products can be placed below the arrow, often with a minus sign. Retrosynthetic analysis can be applied to design a complex synthesis reaction. Here the analysis starts from the products, for example by splitting selected chemical bonds, to arrive at plausible initial reagents. A special arrow (⇒)
26520-460: The reaction rate of many of the steps in the cycle, and therefore increases flux throughout the pathway. Transcriptional regulation . There is a link between intermediates of the citric acid cycle and the regulation of hypoxia-inducible factors ( HIF ). HIF plays a role in the regulation of oxygen homeostasis , and is a transcription factor that targets angiogenesis , vascular remodeling , glucose utilization, iron transport and apoptosis . HIF
26690-477: The reaction. They require less energy to proceed in the forward direction. Reactions are usually written as forward reactions in the direction in which they are spontaneous. Examples: Reactions that proceed in the backward direction to approach equilibrium are often called non-spontaneous reactions , that is, Δ G {\displaystyle \Delta G} is positive, which means that if they occur at constant temperature and pressure, they increase
26860-430: The removal of the amino group by a transaminase . The amino group is fed into the urea cycle , leaving a deaminated carbon skeleton in the form of a keto acid . Several of these keto acids are intermediates in the citric acid cycle, for example α- ketoglutarate formed by deamination of glutamate . The glucogenic amino acids can also be converted into glucose, through gluconeogenesis . In oxidative phosphorylation,
27030-404: The so-called "glucogenic" amino acids. De-aminated alanine, cysteine, glycine, serine, and threonine are converted to pyruvate and can consequently either enter the citric acid cycle as oxaloacetate (an anaplerotic reaction) or as acetyl-CoA to be disposed of as CO 2 and water. In fat catabolism , triglycerides are hydrolyzed to break them into fatty acids and glycerol . In the liver
27200-627: The source of constructed molecules in their cells. Autotrophs such as plants can construct the complex organic molecules in their cells such as polysaccharides and proteins from simple molecules like carbon dioxide and water. Heterotrophs , on the other hand, require a source of more complex substances, such as monosaccharides and amino acids, to produce these complex molecules. Organisms can be further classified by ultimate source of their energy: photoautotrophs and photoheterotrophs obtain energy from light, whereas chemoautotrophs and chemoheterotrophs obtain energy from oxidation reactions. Photosynthesis
27370-464: The starting materials, end products, and sometimes intermediate products and reaction conditions. Chemical reactions happen at a characteristic reaction rate at a given temperature and chemical concentration. Some reactions produce heat and are called exothermic reactions , while others may require heat to enable the reaction to occur, which are called endothermic reactions . Typically, reaction rates increase with increasing temperature because there
27540-425: The substrate can be acceptors, the polysaccharides produced can have straight or branched structures. The polysaccharides produced can have structural or metabolic functions themselves, or be transferred to lipids and proteins by the enzymes oligosaccharyltransferases . Fatty acids are made by fatty acid synthases that polymerize and then reduce acetyl-CoA units. The acyl chains in the fatty acids are extended by
27710-729: The sum of all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary (or intermediate) metabolism. Metabolic reactions may be categorized as catabolic —the breaking down of compounds (for example, of glucose to pyruvate by cellular respiration ); or anabolic —the building up ( synthesis ) of compounds (such as proteins, carbohydrates, lipids, and nucleic acids). Usually, catabolism releases energy, and anabolism consumes energy. The chemical reactions of metabolism are organized into metabolic pathways , in which one chemical
27880-826: The table below. Organic molecules are used as a source of hydrogen atoms or electrons by organotrophs , while lithotrophs use inorganic substrates. Whereas phototrophs convert sunlight to chemical energy , chemotrophs depend on redox reactions that involve the transfer of electrons from reduced donor molecules such as organic molecules , hydrogen , hydrogen sulfide or ferrous ions to oxygen , nitrate or sulfate . In animals, these reactions involve complex organic molecules that are broken down to simpler molecules, such as carbon dioxide and water. Photosynthetic organisms, such as plants and cyanobacteria , use similar electron-transfer reactions to store energy absorbed from sunlight. The most common set of catabolic reactions in animals can be separated into three main stages. In
28050-407: The tissue through glycogenesis which was usually being used to maintained glucose level in blood. Polysaccharides and glycans are made by the sequential addition of monosaccharides by glycosyltransferase from a reactive sugar-phosphate donor such as uridine diphosphate glucose (UDP-Glc) to an acceptor hydroxyl group on the growing polysaccharide. As any of the hydroxyl groups on the ring of
28220-522: The total net production of ATP to approximately 30. An assessment of the total ATP yield with newly revised proton-to-ATP ratios provides an estimate of 29.85 ATP per glucose molecule. While the citric acid cycle is in general highly conserved, there is significant variability in the enzymes found in different taxa (note that the diagrams on this page are specific to the mammalian pathway variant). Some differences exist between eukaryotes and prokaryotes. The conversion of D- threo -isocitrate to 2-oxoglutarate
28390-480: The transfer of heat and work . The second law of thermodynamics states that in any isolated system , the amount of entropy (disorder) cannot decrease. Although living organisms' amazing complexity appears to contradict this law, life is possible as all organisms are open systems that exchange matter and energy with their surroundings. Living systems are not in equilibrium , but instead are dissipative systems that maintain their state of high complexity by causing
28560-407: The type that produces ATP (ADP-forming succinyl-CoA synthetase). Several of the enzymes in the cycle may be loosely associated in a multienzyme protein complex within the mitochondrial matrix . The GTP that is formed by GDP-forming succinyl-CoA synthetase may be utilized by nucleoside-diphosphate kinase to form ATP (the catalyzed reaction is GTP + ADP → GDP + ATP). Products of the first turn of
28730-465: The waste product carbon dioxide. When oxygen is lacking, or when pyruvate is temporarily produced faster than it can be consumed by the citric acid cycle (as in intense muscular exertion), pyruvate is converted to lactate by the enzyme lactate dehydrogenase , a process that also oxidizes NADH back to NAD for re-use in further glycolysis, allowing energy production to continue. The lactate is later converted back to pyruvate for ATP production where energy
28900-456: Was a central goal for medieval alchemists. Examples include the synthesis of ammonium chloride from organic substances as described in the works (c. 850–950) attributed to Jābir ibn Ḥayyān , or the production of mineral acids such as sulfuric and nitric acids by later alchemists, starting from c. 1300. The production of mineral acids involved the heating of sulfate and nitrate minerals such as copper sulfate , alum and saltpeter . In
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