The citric acid cycle is the hub of the metabolism, a central wheel from which many spokes radiate. Also known as the tricarboxylic acid cycle (TCA) or Krebs cycle, it is the final common pathway for the oxidative degradation of fuel molecules and also the source of many biosynthetic precursors. As a degradative pathway, the cycle results stoichiometrically in the complete oxidation of an activated acetyl unit to CO2. With each turn of the cycle three NAD+ molecules and one FAD molecule are reduced which may subsequently donate their electrons to the electron transport system of the mitochondrial matrix, producing ATP. Additionally, with each turn of the cycle, one high energy phosphate bond is created by direct substrate level phosphorylation.
Conceptual Vocabulary for The Citric Acid Cycle
Terminology for glycolysis, citric acid cycle, and oxidative phosphorylation.
An aerobic organism is an organism that has an oxygen based metabolism.
An anaerobic organism is any organism that does not require oxygen for growth.
Adenosine triphosphate is a multifunctional nucleotide that is most important as a molecular currency of intracellular energy transfer.
The citric acid cycle, also known as the tricarboxylic acid cycle or Krebs cycle, is a series of enzyme-catalysed chemical reactions of central importance in all living cells that use oxygen as part of cellular respiration.
Glucose, a monosaccharide, is an important carbohydrate in biology, used by the living cell as a source of energy and metabolic intermediates. It is one of the main products of photosynthesis and starts cellular respiration in both prokaryotes and eukaryotes.
Glycolysis is the initial process of most carbohydrate catabolism serving the functions of producing ATP and NADH, pyruvate for the citric acid cycle, and a variety of other compounds which are important for biosynthesis.
Pyruvic acid is an alpha-keto acid which plays an important role in biochemical processes. It is an output of glycolysis.
Acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main use is to convey the carbon atoms within the acetyl group to the Krebs Cycle to be oxidized for energy production.
Fermentation is respiration under anaerobic conditions with no external electron acceptor.
Ethanol fermentation is the biological process by which sugars such as glucose, fructose, and sucrose, are converted into ethanol and carbon dioxide.
An electron transport chain associates electron carriers and mediating biochemical reactions that produce ATP.
The outer mitochondrial membrane encloses the entire mitochondrion.
The intermembrane space is the region between the inner membrane and the outer membrane of a mitochondrion or a chloroplast.
A kinase, alternatively known as a phosphotransferase, is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific target molecules.
Phosphorylation is the addition of a phosphate group to a protein molecule or a small molecule.
Glucose 6-phosphate, also known as Robison ester, is glucose sugar phosphorylated on carbon 6. Yhe vast majority of glucose entering a cell will become phosphorylated in this way.
Fructose 6-phosphate (also known as the Neuberg ester) is fructose sugar phosphorylated on carbon 6. The beta-D-form of this compound is very common in cells.
Nicotinamide adenine dinucleotide is an important coenzyme found in cells, which plays key roles as a carrier of electrons and a participant in metabolic redox reactions, as well as in cell signaling.
L-lactate is constantly produced in animals from pyruvate in a process of fermentation during normal metabolism and exercise.
Lactic acid fermentation is a form of anaerobic respiration that occurs in some bacteria and animal cells in the absence of oxygen.
Adenosine monophosphate is an ester of phosphoric acid with the nucleoside adenosine. AMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase adenine.
Substrate-level phosphorylation is a type of chemical reaction that results in the formation of ATP by the direct transfer of a phosphate group to ADP from a reactive intermediate.
The pyruvate decarboxylation reaction links the metabolic pathways glycolysis and the citric acid cycle.
Chemiosmosis is the diffusion of ions across a selectively-permeable membrane, often specifically with reference to the generation of ATP by the movement of hydrogen ions across a membrane during cellular respiration.
Cristae are the internal compartments formed by the inner membrane of a mitochondrion.
The matrix of the mitochondrion is the compartment containing soluble enzymes that catalyze the oxidation of pyruvate and other small organic molecules.
The inner mitochondrial membrane forms internal compartments known as cristae, which allow greater space for the proteins such as cytochromes to function properly and efficiently.
A proton pump is an integral membrane protein that is capable of moving protons across the membrane of a cell, mitochondrion, or other subcellular compartment.
Phosphofructokinase 1 is a kinase enzyme which acts upon Fructose 6-phosphate. It is the most important regulatory enzyme of glycolysis.
An ATP synthase is a general term for an enzyme that can synthesize adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate by utilizing some form of energy.
Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce ATP.
Cytochromes are generally membrane-bound hemoproteins that contain heme groups and carry out electron transport.
Dihydroxyacetone phosphate (DHAP) is one of the two products of breakdown of fructose 1,6-phosphate in glycolysis, along with glyceraldehyde 3-phosphate.
Glyceraldehyde 3-phosphate is one of the two products of breakdown of fructose 1,6-phosphate in glycolysis, along with dihydroxyacetone phosphate.
Phosphoenolpyruvate (PEP) has the highest energy phosphate bond found in living organisms. It is formed in glycolysis by the action of the enzyme enolase on 2-phosphoglycerate.
Adenylate kinase is a phosphotransferase enzyme that catalyzes the production of ATP from ADP.
Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate.
Glucose isomerase is an enzyme that catalyzes the conversion of glucose into fructose.
The electron carrier, flavin adenine dinucleotide accomodates two equivalents of hydrogen when it is reduced in the citric acid cycle during aerobic respiration.
The malate-aspartate shuttle is a biochemical system for translocating electrons produced during glycolysis across the impermeable inner membrane of the mitochondrion for oxidative phosphorylation in eukaryotes.
The mitochondrial shuttles are systems used to transport reducing agents across the inner mitochondrial membrane.
Thermogenin is an uncoupling protein found in the mitochondria of brown adipose tissue, used to generate heat by non-shivering thermogenesis.
In glycolysis and photosynthesis, 1,3-Bisphosphoglycerate (1,3BPG) is a transitional stage between glycerate 3-phosphate and glyceraldehyde 3-phosphate during the fixation or reduction, respectively, of carbon dioxide.
2-Phosphoglycerate (2PG) is a glyceric acid which serves as the substrate in the ninth step of glycolysis. It is catalyzed by enolase into phosphoenolpyruvate (PEP), the penultimate step in the conversion of glucose to pyruvate.
The Cori cycle refers to the cycling of lactate produced by red blood cells and muscle (during anaerobic respiration) back into glucose.
The anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates.
A hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate.
Enolase, or 2-phospho-D-glycerate hydrolyase, is an enzyme that participates in glycolysis, catalyzing the conversion of 2-phosphoglycerate to phosphoenolpyruvate, the penultimate step in the conversion of glucose to pyruvate.
Pyruvate kinase is an enzyme involved in glycolysis, catalyzing the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP, yielding a pyruvate molecule and producing one molecule ATP.
Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that transform pyruvate into acetyl-CoA.
Oxaloacetate is formed in the citric acid cycle upon oxidation of L-malate, and reacts with Acetyl-CoA to form citrate, catalysed by citrate synthase.
The enzyme citrate synthase is a pace-maker enzyme, controlling the first committed step of the Krebs cycle.
The enzyme cytochrome c oxidase is the last protein in the electron transport chain. It receives an electron from each of four cytochrome c molecules, and transfers them to one oxygen molecule.
Coenzyme Q - cytochrome c reductase catalyzes the reduction of cytochrome c by oxidation of coenzyme Q and the concomitant pumping of 4 protons from the mitochondrial matrix to the intermembrane space.
NADH dehydrogenase is an enzyme located in the inner mitochodrial membrane that catalyzes the transfer of electrons from NADH to coenzyme Q.
Beta oxidation is the process by which fatty acids, in the form of Acyl-CoA molecules, are broken down in the mitochondria and/or in peroxisomes to generate Acetyl-CoA, the entry molecule for the Krebs Cycle.
Ketosis is a stage in metabolism occurring when the liver converts fat into fatty acids and ketone bodies which can be used by the body for energy.
Ketone bodies are three water soluble compounds that are produced as by-products when fatty acids are broken down for energy. They are used as a source of energy in the heart and brain.
The Entner-Doudoroff pathway in some prokaryotes describes a series of reactions that catabolize glucose to pyruvate using a different set of enzymes from those used in either glycolysis or the pentose phosphate pathway.
Aldolase A is an enzyme which catalyses one of the aldol reactions of glycolysis in which fructose 1,6-bisphosphate is broken down into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.
Triosephosphate isomerase is an enzyme in glycolysis that catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate.
Phosphoglycerate kinase is a transferase enzyme used in the seventh step of glycolysis, transfering a phosphate group from 1,3-biphosphoglycerate to ADP, forming ATP and 3-Phosphoglycerate.
Phosphoglycerate mutase is an enzyme that catalyzes step 8 of glycolysis: the internal transfer of a phosphate group from C-3 to C-2 which results in the conversion of 3-phosphoglycerate to 2-phosphoglycerate.
Isocitrate is formed from citrate in the citric acid cycle with the help of the enzyme aconitase
Aconitase is an enzyme that catalyses the stereo-specific isomerization of citrate to isocitrate via cis-aconitate in the tricarboxylic acid cycle, a non-redox-active process.
Isocitrate dehydrogenase is an enzyme which participates in the citric acid cycle, catalyzing the third step of the cycle: the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate and carbon dioxide while converting NAD+ to NADH.
Succinate-coenzyme Q reductase is an enzyme complex bound to the inner mitochondrial membrane. This is the only enzyme that participates in both the citric acid cycle and the mitochondrial electron transport chain
Malate dehydrogenase is an enzyme in the citric acid cycle that catalyzes the conversion of malate into oxaloacetate (using NAD+) and vice versa.
An iron-sulfur cluster is a structural motif found in a variety of metalloproteins, such as the ferredoxins, as well as NADH dehydrogenase and Coenzyme Q - cytochrome c reductase, and nitrogenase.
Electron-transferring-flavoprotein dehydrogenase is an enzyme that transfers electrons from electron-transferring flavoprotein in the mitochondrial matrix to the ubiquinone pool in the inner mitochondrial membrane.
Acyl CoA dehydrogenase is the enzyme used to catalyze the first step of beta-oxidation in fatty acid metabolism.
In the citric acid cycle, succinyl coenzyme A synthetase catalyzes the formation of succinate and coenzyme-A, a 4-carbon metabolite, from succinyl-CoA.
Fumarase is an enzyme involved in the Krebs Cycle that catalyzes the hydration of fumarate to L-malate.
The proto-mitochondrion is the ancestral bacterial endosymbiont from which all mitochondria are thought to be derived.
Flavin mononucleotide is derived from riboflavin and functions as cofactor of various oxidoreductases including NADH dehydrogenase.
Enoyl-CoA hydratase is the enzyme used to catalyze the second step of beta-oxidation in fatty acid metabolism.
The third step of beta oxidation in fatty acid metablism is the oxidation of L-3-hydroxyacyl CoA by NAD+, which is catalyzed by 3-Hydroxyacyl CoA dehydrogenase.
The final step of beta oxidation in fatty acid metablism is the cleavage of 3-ketoacyl CoA by the thiol group of another molecule of CoA, which is catalyzed by Acetyl-CoA C-acyltransferase.
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