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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]
When the body has no free carbohydrates available, fat must be broken down into acetyl-CoA in order to get energy. Under these conditions, acetyl-CoA cannot be metabolized through the citric acid cycle because the citric acid cycle intermediates (mainly oxaloacetate) have been depleted to feed the gluconeogenesis pathway. The resulting ...
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]
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.
Aside from the role of PC in gluconeogenesis, PC serves an anaplerotic role (an enzyme catalyzed reaction that can replenish the supply of intermediates in the citric acid cycle) for the tricarboxylic acid cycle (essential to provide oxaloacetate), when intermediates are removed for different biosynthetic purposes.
To cataplerotically remove oxaloacetate from the citric cycle, malate can be transported from the mitochondrion into the cytoplasm, decreasing the amount of oxaloacetate that can be regenerated. [48] Furthermore, citric acid intermediates are constantly used to form a variety of substances such as the purines, pyrimidines and porphyrins. [48]
Malate dehydrogenase is also involved in gluconeogenesis, the synthesis of glucose from smaller molecules. Pyruvate in the mitochondria is acted upon by pyruvate carboxylase to form oxaloacetate, a citric acid cycle intermediate. In order to get the oxaloacetate out of the mitochondria, malate dehydrogenase reduces it to malate, and it then ...
Secondly, 2-oxoglutarate can enter the tricarboxylic acid cycle to generate oxaloacetate. Therefore, theoretically any metabolites in the TCA cycle or any metabolites generating the metabolites of the TCA cycle can be used as a precursor of glyceroneogenesis, but glutamate is the only precursor confirmed.