C0008858 - The Krebs cycle, also called the citric acid cycle, is a fundamental metabolic pathway involving eight enzymes essential for energy production through aerobic respiration, and, like glycolysis, arose early in evolution. This pathway is also an important source of biosynthetic building blocks used in gluconeogenesis, amino acid biosynthesis, and fatty acid biosynthesis. The Krebs cycle takes place in mitochondria where it oxidizes acetyl-CoA, releasing carbon dioxide and extracting energy primarily as the reduced high-energy electron carriers NADH and FADH2. NADH and FADH2 transfer chemical energy from metabolic intermediates to the electron transport chain to create a different form of energy, a gradient of protons across the inner mitochondrial membrane. The energy of the proton gradient in turn drives synthesis of the high-energy phosphate bonds in ATP, the common energy currency of the cell used to drive a huge variety of reactions and processes. An acetyl-CoA molecule (2 carbons) enters the cycle when citrate synthase condenses it with oxaloacetate (4 carbons) to create citrate (6 carbons). One source of the acetyl-CoA that enters the Krebs cycle is the conversion of pyruvate from glycolysis to acetyl-CoA by pyruvate dehydrogenase. Acetyl-CoA is a key metabolic junction, derived not only from glycolysis but also from the oxidation of fatty acids. As the cycle proceeds, the Krebs cycle intermediates are oxidized, transferring their energy to create reduced NADH and FADH2. The oxidation of the metabolic intermediates of the pathway also releases two carbon dioxide molecules for each acetyl-CoA that enters the cycle, leaving the net carbons the same with each turn of the cycle. This carbon dioxide, along with more released by pyruvate dehydrogenase, is the source of CO2 released into the atmosphere when you breathe. The Krebs cycle, like other metabolic pathways, is tightly regulated to efficiently meet the needs of the cell and the organism. The irreversible synthesis of acetyl-CoA from pyruvate by pyruvate dehydrogenase is one important regulatory step, and is inhibited by high concentrations of ATP that indicate abundant energy. Citrate synthase, alpha-ketoglutarate dehydrogenase and isocitrate dehydrogenase are all key regulatory steps in the cycle and are each inhibited by abundant energy in the cell, indicated through high concentrations of ATP or NADH. The activity of the Krebs cycle is closely linked to the availability of oxygen, although none of the steps in the pathway directly use oxygen. Oxygen is required for the electron transport chain to function, which recycles NADH back to NAD+ and FADH2 back to FADH, providing NAD+ and ADH required by enzymes in the Krebs cycle. If the oxygen supply to a muscle cell or a yeast cell is low, NAD+ and FADH levels fall, the Krebs cycle cannot proceed forward, and the cell must resort to fermentation to continue making ATP. Some Krebs cycle enzymes require non-protein cofactors for activity, such as thiamine, vitamin B1. Insufficient quantities of this vitamin in the diet leads to decreased activity of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, and a decrease in the ability of the Krebs cycle to meet metabolic demands, causing the disease beriberi. Although the elucidation of the Krebs cycle remains one of the landmarks of biochemistry, aspects of the Krebs cycle and its enzymes are still actively researched in the modern proteomic era. (This definition may be outdated

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Lang Dictionary CODE			LUI	preferred no	SUI	preference Yes / No	Terms, descriptions
							CUI C0008858

Russian	Medical Subject Headings Russian	D002952	L3355315	preferred	S3882796	Y	ЛИМОННОЙ КИСЛОТЫ ЦИКЛ
Russian	Medical Subject Headings Russian	D002952	L0898294	no	S1102111	Y	LIMONNOI KISLOTY TSIKL
Russian	Medical Subject Headings Russian	D002952	L1527058	no	S1822967	Y	KREBSA TSIKL
Russian	Medical Subject Headings Russian	D002952	L1546565	no	S1842474	Y	TSIKL KREBSA
Russian	Medical Subject Headings Russian	D002952	L1546566	no	S1842475	Y	TSIKL TRIKARBONOVYKH KISLOT
Russian	Medical Subject Headings Russian	D002952	L3353788	no	S3881271	Y	КРЕБСА ЦИКЛ
Russian	Medical Subject Headings Russian	D002952	L3376178	no	S3903703	Y	ЦИКЛ КРЕБСА
Russian	Medical Subject Headings Russian	D002952	L3376180	no	S3903762	Y	ЦИКЛ ТРИКАРБОНОВЫХ КИСЛОТ
	Medical Subject Headings				A0039655	AT53895957	A series of oxidative reactions in the breakdown of acetyl units derived from GLUCOSE; FATTY ACIDS; or AMINO ACIDS by means of tricarboxylic acid intermediates. The end products are CARBON DIOXIDE, water, and energy in the form of phosphate bonds.
	(CPTSP) CRISP Thesaurus				A0318173	AT51222881	series of reactions involving oxidation of a two-carbon acetyl unit to carbon dioxide and water with the production of high-energy phosphate bonds by means of tricarboxylic acid intermediate.
	Gene Ontology				A11613724	AT148902580	A nearly universal metabolic pathway in which the acetyl group of acetyl coenzyme A is effectively oxidized to two CO2 and four pairs of electrons are transferred to coenzymes. The acetyl group combines with oxaloacetate to form citrate, which undergoes successive transformations to isocitrate, 2-oxoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate again, thus completing the cycle. In eukaryotes the tricarboxylic acid is confined to the mitochondria. See also glyoxylate cycle. [ISBN:0198506732]
	NCI BioCarta online maps of molecular pathways, adapted for NCI use				A19045261	AT224196295	The Krebs cycle, also called the citric acid cycle, is a fundamental metabolic pathway involving eight enzymes essential for energy production through aerobic respiration, and, like glycolysis, arose early in evolution. This pathway is also an important source of biosynthetic building blocks used in gluconeogenesis, amino acid biosynthesis, and fatty acid biosynthesis. The Krebs cycle takes place in mitochondria where it oxidizes acetyl-CoA, releasing carbon dioxide and extracting energy primarily as the reduced high-energy electron carriers NADH and FADH2. NADH and FADH2 transfer chemical energy from metabolic intermediates to the electron transport chain to create a different form of energy, a gradient of protons across the inner mitochondrial membrane. The energy of the proton gradient in turn drives synthesis of the high-energy phosphate bonds in ATP, the common energy currency of the cell used to drive a huge variety of reactions and processes. An acetyl-CoA molecule (2 carbons) enters the cycle when citrate synthase condenses it with oxaloacetate (4 carbons) to create citrate (6 carbons). One source of the acetyl-CoA that enters the Krebs cycle is the conversion of pyruvate from glycolysis to acetyl-CoA by pyruvate dehydrogenase. Acetyl-CoA is a key metabolic junction, derived not only from glycolysis but also from the oxidation of fatty acids. As the cycle proceeds, the Krebs cycle intermediates are oxidized, transferring their energy to create reduced NADH and FADH2. The oxidation of the metabolic intermediates of the pathway also releases two carbon dioxide molecules for each acetyl-CoA that enters the cycle, leaving the net carbons the same with each turn of the cycle. This carbon dioxide, along with more released by pyruvate dehydrogenase, is the source of CO2 released into the atmosphere when you breathe. The Krebs cycle, like other metabolic pathways, is tightly regulated to efficiently meet the needs of the cell and the organism. The irreversible synthesis of acetyl-CoA from pyruvate by pyruvate dehydrogenase is one important regulatory step, and is inhibited by high concentrations of ATP that indicate abundant energy. Citrate synthase, alpha-ketoglutarate dehydrogenase and isocitrate dehydrogenase are all key regulatory steps in the cycle and are each inhibited by abundant energy in the cell, indicated through high concentrations of ATP or NADH. The activity of the Krebs cycle is closely linked to the availability of oxygen, although none of the steps in the pathway directly use oxygen. Oxygen is required for the electron transport chain to function, which recycles NADH back to NAD+ and FADH2 back to FADH, providing NAD+ and ADH required by enzymes in the Krebs cycle. If the oxygen supply to a muscle cell or a yeast cell is low, NAD+ and FADH levels fall, the Krebs cycle cannot proceed forward, and the cell must resort to fermentation to continue making ATP. Some Krebs cycle enzymes require non-protein cofactors for activity, such as thiamine, vitamin B1. Insufficient quantities of this vitamin in the diet leads to decreased activity of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, and a decrease in the ability of the Krebs cycle to meet metabolic demands, causing the disease beriberi. Although the elucidation of the Krebs cycle remains one of the landmarks of biochemistry, aspects of the Krebs cycle and its enzymes are still actively researched in the modern proteomic era. (This definition may be outdated - see the DesignNote.)