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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]
Other glucogenic amino acids and all citric acid cycle intermediates (through conversion to oxaloacetate) can also function as substrates for gluconeogenesis. [9] Generally, human consumption of gluconeogenic substrates in food does not result in increased gluconeogenesis. [10] In ruminants, propionate is the principal gluconeogenic substrate.
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.
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.
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]
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.
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 ...
Instead the acetyl-CoA produced by the beta-oxidation of fatty acids condenses with oxaloacetate, to enter the citric acid cycle. During each turn of the cycle, two carbon atoms leave the cycle as CO 2 in the decarboxylation reactions catalyzed by isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase. Thus each turn of the citric acid ...