Substrates Of Gluconeogenesis
The major substrates of gluconeogenesis are lactate, glycerol, and glucogenic amino acids.
Lactate is a product of anaerobic glycolysis. This ATP-generating process occurs when oxygen is limited, eg, during vigorous exercise or low-perfusion states. Cells that use this pathway, such as the erythrocytes, lack mitochondria and are not equipped for oxidative phosphorylation. The liver uses lactate in the blood to produce glucose via gluconeogenesis. Glucose gets released into the bloodstream, travels back to the erythrocytes and exercising muscles, and is metabolized back into lactate. This process is called the Cori cycle.[2]
Glycerol comes from adipose tissue lipolysis. This process breaks down triglycerides to form fatty acids and glycerol molecules. In the liver, glycerol kinase phosphorylates glycerol to form glycerol phosphate. Glycerol phosphate dehydrogenase oxidizes glycerol phosphate into the glycolytic intermediate, DHAP.[3]
Glucogenic amino acids enter the gluconeogenesis pathway via the citric acid cycle (see Image. Glucogenic Amino Acids). The first step is the deamination of the glucogenic amino acids into α-ketoacids, which are substrates in the citric acid cycle. From there, these α-ketoacids are converted to oxaloacetate, the substrate for PEPCK.
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