Gluconeogenesis is the production of glucose from non-carbohydrate substances such as pyruvic acid, lactic acid, glycogenic amino acids, propionic acid, and glycerol by humans and animals using the secretion of glucagon as a signal. Means and routes.
If the diet is biased toward meat, the nutrition intake is biased toward protein and fat, and the intake of sugar, which is also one of the three major nutrients, is insufficient. Carnivorous animals such as cats have higher enzymatic activity of gluconeogenesis than omnivorous animals such as dogs, and perform gluconeogenesis from glycogenic amino acids obtained by decomposition from proteins to produce the necessary sugars in the body. is doing.
In the case of ruminants, gluconeogenesis from propionic acid is a particularly important metabolism, as bacteria that break down cellulose turn sugar into volatile fatty acids in the stomach.
Six molecules of ATP are required to generate one molecule of glucose. Most are liver cells and some are kidneys.
Most cells are unable to produce free glucose due to the lack of expression of glucose-6-phosphatase, the only enzyme involved in glucose uptake and catabolism. Only hepatocytes with glucose-6-phosphatase and the small intestine and kidney under severe starvation conditions dislodge the phosphate group of glucose-6-phosphate produced by the gluconeogenic reaction to produce free glucose. It is possible to release free glucose into the blood vessels. As soon as glucose is taken up by cells, phosphorylation occurs and glucose-6-phosphate is produced in order to prevent glucose from diffusing beyond the cell membrane. Glucose-6-phosphate cannot easily cross cell membranes because charge is introduced by phosphorylation.
The phenomenon that causes hyperglycemia due to rapid gluconeogenesis is called the somogy effect. It was revealed in the 1850s by the French physiologist Claude Bernard. In addition, when fasting is performed, muscles are decomposed to compensate for sugar deficiency, gluconeogenesis occurs, and metabolism decreases due to muscle loss.
Path of gluconeogenesis
The reaction proceeds almost along the reverse reaction of glycolysis, but since there is also an irreversible reaction, the overall reaction is not the reverse of glycolysis. The irreversible reaction is caused by another method. The reaction is shown below.
Pyruvic acid → Phosphoenolpyruvic acid
The reaction is proceeding via the citric acid cycle. This reaction takes four steps, the first two steps in the mitochondria and the rest in the cytoplasm. In mitochondria, pyruvate carboxylase acts on pyruvate to form oxaloacetate, which is an intermediate in the citric acid cycle. Since oxaloacetate cannot pass through the inner membrane of mitochondria as it is, the transport of phosphoenolpyruvate from mitochondria to the cytoplasm is mediated by the malate / phosphoenolpyruvate shuttle.
Then, oxaloacetate is reduced to malic acid by malate dehydrogenase to get out of the mitochondria, and passes through the inner mitochondrial membrane as malic acid. It is again oxidized to oxaloacetate by malate dehydrogenase in the cytoplasm outside the mitochondria and eventually converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase (PEPCK). Overall the Gibbs energy of this reaction