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Names | |
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Preferred IUPAC name 2-Oxobutanedioic acid | |
Other names Oxaloacetic acid Oxalacetic acid 2-Oxosuccinic acid Ketosuccinic acid | |
Identifiers | |
3D model (JSmol) | |
ChEBI | |
ChemSpider | |
ECHA InfoCard | 100.005.755 |
EC Number |
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KEGG | |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C4H4O5 | |
Molar mass | 132.07 g/mol |
Density | 1.6 g/cm3 |
Melting point | 161 °C (322 °F; 434 K) |
Thermochemistry | |
Std enthalpy of formation (ΔfH⦵298) | -943.21 kJ/mol |
Std enthalpy of combustion (ΔcH⦵298) | -1205.58 kJ/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes that occur in animals. It takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, fatty acid synthesis and the citric acid cycle. [1]
Oxaloacetic acid undergoes successive deprotonations to give the dianion:
At high pH, the enolizable proton is ionized:
The enol forms of oxaloacetic acid are particularly stable. Keto-enol tautomerization is catalyzed by the enzyme oxaloacetate tautomerase. trans-Enol-oxaloacetate also appears when tartrate is the substrate for fumarase. [2]
Oxaloacetate forms in several ways in nature. A principal route is upon oxidation of L-malate, catalyzed by malate dehydrogenase, in the citric acid cycle. Malate is also oxidized by succinate dehydrogenase in a slow reaction with the initial product being enol-oxaloacetate. [3]
It also arises from the condensation of pyruvate with carbonic acid, driven by the hydrolysis of ATP:
Occurring in the mesophyll of plants, this process proceeds via phosphoenolpyruvate, catalysed by phosphoenolpyruvate carboxylase.
Oxaloacetate can also arise from trans- or de- amination of aspartic acid.
Oxaloacetate is an intermediate of the citric acid cycle, where it reacts with acetyl-CoA to form citrate, catalyzed by citrate synthase. It is also involved in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, and fatty acid synthesis. Oxaloacetate is also a potent inhibitor of complex II.
Gluconeogenesis [1] is a metabolic pathway consisting of a series of eleven enzyme-catalyzed reactions, resulting in the generation of glucose from non-carbohydrates substrates. The beginning of this process takes place in the mitochondrial matrix, where pyruvate molecules are found. A pyruvate molecule is carboxylated by a pyruvate carboxylase enzyme, activated by a molecule each of ATP and water. This reaction results in the formation of oxaloacetate. NADH reduces oxaloacetate to malate. This transformation is needed to transport the molecule out of the mitochondria. Once in the cytosol, malate is oxidized to oxaloacetate again using NAD+. Then oxaloacetate remains in the cytosol, where the rest of reactions will take place. Oxaloacetate is later decarboxylated and phosphorylated by phosphoenolpyruvate carboxykinase and becomes 2-phosphoenolpyruvate using guanosine triphosphate (GTP) as phosphate source. Glucose is obtained after further downstream processing.
The urea cycle is a metabolic pathway that results in the formation of urea using one ammonium molecule from degraded amino acids, another ammonium group from aspartate and one bicarbonate molecule. [1] This route commonly occurs in hepatocytes. The reactions related to the urea cycle produce NADH, and NADH can be produced in two different ways. One of these uses oxaloacetate. In the cytosol there are fumarate molecules. Fumarate can be transformed into malate by the actions of the enzyme fumarase. Malate is acted on by malate dehydrogenase to become oxaloacetate, producing a molecule of NADH. After that, oxaloacetate will be recycled to aspartate, as transaminases prefer these keto acids over the others. This recycling maintains the flow of nitrogen into the cell.
The glyoxylate cycle is a variant of the citric acid cycle. [4] It is an anabolic pathway occurring in plants and bacteria utilizing the enzymes isocitrate lyase and malate synthase. Some intermediate steps of the cycle are slightly different from the citric acid cycle; nevertheless oxaloacetate has the same function in both processes. [1] This means that oxaloacetate in this cycle also acts as the primary reactant and final product. In fact the oxaloacetate is a net product of the glyoxylate cycle because its loop of the cycle incorporates two molecules of acetyl-CoA.
In previous stages acetyl-CoA is transferred from the mitochondria to the cytoplasm where fatty acid synthase resides. The acetyl-CoA is transported as a citrate, which has been previously formed in the mitochondrial matrix from acetyl-CoA and oxaloacetate. This reaction usually initiates the citric acid cycle, but when there is no need of energy it is transported to the cytoplasm where it is broken down to cytoplasmic acetyl-CoA and oxaloacetate.
Another part of the cycle requires NADPH for the synthesis of fatty acids. [5] Part of this reducing power is generated when the cytosolic oxaloacetate is returned to the mitochondria as long as the internal mitochondrial layer is non-permeable for oxaloacetate. Firstly the oxaloacetate is reduced to malate using NADH. Then the malate is decarboxylated to pyruvate. Now this pyruvate can easily enter the mitochondria, where it is carboxylated again to oxaloacetate by pyruvate carboxylase. In this way, the transfer of acetyl-CoA that is from the mitochondria into the cytoplasm produces a molecule of NADH. The overall reaction, which is spontaneous, may be summarized as:
Six essential amino acids and three nonessential are synthesized from oxaloacetate and pyruvate. [6] Aspartate and alanine are formed from oxaloacetate and pyruvate, respectively, by transamination from glutamate. Asparagine is synthesized by amidation of aspartate, with glutamine donating the NH4. These are nonessential amino acids, and their simple biosynthetic pathways occur in all organisms. Methionine, threonine, lysine, isoleucine, valine, and leucine are essential amino acids in humans and most vertebrates. Their biosynthetic pathways in bacteria are complex and interconnected.
Oxaloacetate produces oxalate by hydrolysis. [7]
This process is catalyzed by the enzyme oxaloacetase. This enzyme is seen in plants, but is not known in the animal kingdom. [8]
Click on genes, proteins and metabolites below to link to respective articles. [§ 1] Glycolysis and Gluconeogenesis edit
| Click on genes, proteins and metabolites below to link to respective articles. [§ 1] TCACycle_WP78 edit
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The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle or the 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, and proteins. The chemical energy released is available under the form of ATP. The Krebs cycle 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 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.
Glycolysis is the metabolic pathway that converts glucose into pyruvate and, in most organisms, occurs in the liquid part of cells. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.
The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic.
Pyruvic acid (IUPAC name: 2-oxopropanoic acid, also called acetoic acid) (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Cellular respiration is the process by which biological fuels are oxidized in the presence of an inorganic electron acceptor, such as oxygen, to drive the bulk production of adenosine triphosphate (ATP), which contains energy. Cellular respiration may be described as a set of metabolic reactions and processes that take place in the cells of organisms to convert chemical energy from nutrients into ATP, and then release waste products.
Acetyl-CoA is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle to be oxidized for energy production.
Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise.
The term amphibolism is used to describe a biochemical pathway that involves both catabolism and anabolism. Catabolism is a degradative phase of metabolism in which large molecules are converted into smaller and simpler molecules, which involves two types of reactions. First, hydrolysis reactions, in which catabolism is the breaking apart of molecules into smaller molecules to release energy. Examples of catabolic reactions are digestion and cellular respiration, where sugars and fats are broken down for energy. Breaking down a protein into amino acids, or a triglyceride into fatty acids, or a disaccharide into monosaccharides are all hydrolysis or catabolic reactions. Second, oxidation reactions involve the removal of hydrogens and electrons from an organic molecule. Anabolism is the biosynthesis phase of metabolism in which smaller simple precursors are converted to large and complex molecules of the cell. Anabolism has two classes of reactions. The first are dehydration synthesis reactions; these involve the joining of smaller molecules together to form larger, more complex molecules. These include the formation of carbohydrates, proteins, lipids and nucleic acids. The second are reduction reactions, in which hydrogens and electrons are added to a molecule. Whenever that is done, molecules gain energy.
Malate dehydrogenase (EC 1.1.1.37) (MDH) is an enzyme that reversibly catalyzes the oxidation of malate to oxaloacetate using the reduction of NAD+ to NADH. This reaction is part of many metabolic pathways, including the citric acid cycle. Other malate dehydrogenases, which have other EC numbers and catalyze other reactions oxidizing malate, have qualified names like malate dehydrogenase (NADP+).
In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.
Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes that generate energy and (2) anabolic processes where they serve as building blocks for other compounds.
Anaplerotic reactions, a term coined by Hans Kornberg and originating from the Greek ἀνά= 'up' and πληρόω= 'to fill', are chemical reactions that form intermediates of a metabolic pathway. Examples of such are found in the citric acid cycle. In normal function of this cycle for respiration, concentrations of TCA intermediates remain constant; however, many biosynthetic reactions also use these molecules as a substrate. Anaplerosis is the act of replenishing TCA cycle intermediates that have been extracted for biosynthesis.
Pyruvate carboxylase (PC) encoded by the gene PC is an enzyme of the ligase class that catalyzes the physiologically irreversible carboxylation of pyruvate to form oxaloacetate (OAA).
In biochemistry and metabolism, beta oxidation (also β-oxidation) is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA. Acetyl-CoA enters the citric acid cycle, generating NADH and FADH2, which are electron carriers used in the electron transport chain. It is named as such because the beta carbon of the fatty acid chain undergoes oxidation and is converted to a carbonyl group to start the cycle all over again. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes.
Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins.
The glyoxylate cycle, a variation of the tricarboxylic acid cycle, is an anabolic pathway occurring in plants, bacteria, protists, and fungi. The glyoxylate cycle centers on the conversion of acetyl-CoA to succinate for the synthesis of carbohydrates. In microorganisms, the glyoxylate cycle allows cells to use two carbons, such as acetate, to satisfy cellular carbon requirements when simple sugars such as glucose or fructose are not available. The cycle is generally assumed to be absent in animals, with the exception of nematodes at the early stages of embryogenesis. In recent years, however, the detection of malate synthase (MS) and isocitrate lyase (ICL), key enzymes involved in the glyoxylate cycle, in some animal tissue has raised questions regarding the evolutionary relationship of enzymes in bacteria and animals and suggests that animals encode alternative enzymes of the cycle that differ in function from known MS and ICL in non-metazoan species.
Fumarase is an enzyme that catalyzes the reversible hydration/dehydration of fumarate to malate. Fumarase comes in two forms: mitochondrial and cytosolic. The mitochondrial isoenzyme is involved in the Krebs cycle and the cytosolic isoenzyme is involved in the metabolism of amino acids and fumarate. Subcellular localization is established by the presence of a signal sequence on the amino terminus in the mitochondrial form, while subcellular localization in the cytosolic form is established by the absence of the signal sequence found in the mitochondrial variety.
Phosphoenolpyruvate carboxylase (also known as PEP carboxylase, PEPCase, or PEPC; EC 4.1.1.31, PDB ID: 3ZGE) is an enzyme in the family of carboxy-lyases found in plants and some bacteria that catalyzes the addition of bicarbonate (HCO3−) to phosphoenolpyruvate (PEP) to form the four-carbon compound oxaloacetate and inorganic phosphate:
Glutaminolysis (glutamine + -lysis) is a series of biochemical reactions by which the amino acid glutamine is lysed to glutamate, aspartate, CO2, pyruvate, lactate, alanine and citrate.
The citrate-malate shuttle is a series of chemical reactions, commonly referred to as a biochemical cycle or system, that transports acetyl-CoA in the mitochondrial matrix across the inner and outer mitochondrial membranes for fatty acid synthesis. Mitochondria are enclosed in a double membrane. As the inner mitochondrial membrane is impermeable to acetyl-CoA, the shuttle system is essential to fatty acid synthesis in the cytosol. It plays an important role in the generation of lipids in the liver.