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Overview of the citric acid cycle. The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle) [1] [2] —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 citric acid cycle is a series of enzymatic reactions carried out inside the inner membranes of the cell's mitochondria. The process begins when the two-carbon acetyl CoA enters the cycle and joins the four-carbon oxaloacetate to produce the six-carbon citrate.
Citrate synthase (E.C. 2.3.3.1 (previously 4.1.3.7)) is an enzyme that exists in nearly all living cells. It functions as a pace-making enzyme in the first step of the citric acid cycle (or Krebs cycle). [5] Citrate synthase is located within eukaryotic cells in the mitochondrial matrix, but is encoded by nuclear DNA rather than mitochondrial.
Malate, in the mitochondrial matrix, can be used to make pyruvate (catalyzed by malic enzyme) or oxaloacetic acid, both of which can enter the citric acid cycle. Glutamine can also be used to produce oxaloacetate during anaplerotic reactions in various cell types through "glutaminolysis", which is also seen in many c-Myc transformed cells. [3]
[10]: 571 Examples of amphibolic pathways are the citric acid cycle and the glyoxylate cycle. These sets of chemical reactions contain both energy producing and utilizing pathways. [5]: 572 To the right is an illustration of the amphibolic properties of the TCA cycle.
Two low-energy waste products, H 2 O and CO 2, are created during this cycle. [9] [10] The citric acid cycle is an 8-step process involving 18 different enzymes and co-enzymes. During the cycle, acetyl-CoA (2 carbons) + oxaloacetate (4 carbons) yields citrate (6 carbons), which is rearranged to a more reactive form called isocitrate (6 carbons).
Metabolic intermediates are compounds produced during the conversion of substrates (starting molecules) into final products in biochemical reactions within cells. [1]Although these intermediates are of relatively minor direct importance to cellular function, they can play important roles in the allosteric regulation of enzymes, glycolysis, the citric acid cycle, and amino acid synthesis.
The citric acid cycle is an example of a metabolon that facilitates substrate channeling. [1] [2] Another example is the dhurrin synthesis pathway in sorghum, in which the enzymes assemble as a metabolon in lipid membranes. [3]
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