One of the significant processes in the body is gluconeogenesis. This is the name of the metabolic pathway that leads to the fact that glucose is formed from non-carbohydrate compounds (pyruvate in particular).
What are its features? How is this process regulated? There are many important nuances regarding this topic, and now it is worth paying attention to them.
Definition
So, gluconeogenesis is the process of synthesis of glucose from substances that have a non-carbohydrate nature of origin. It proceeds mainly in the liver, a little less intensively - in the renal cortex and intestinal mucosa.
This process includes all reversible glycolysis reactions with specific bypasses. In simple terms, he does not repeat the reactions of glucose oxidation completely. What happens? Gluconeogenesis is a process that can occur in all tissues. The only exception is the 6-phosphatase reaction. It occurs only in the kidneys and liver.
GeneralFeatures
Gluconeogenesis is a process that occurs in microorganisms, fungi, plants and animals. Interestingly, its reactions are the same for all species and tissues.
The most important precursors of glucose in animals are three-carbon compounds. These include glycerol, pyruvate, lactate, and amino acids.
Glucose formed in the process of gluconeogenesis is transported into the blood, and from there to other tissues. What's next? After physical exertion, which the body was subjected to, the lactate formed in the skeletal muscles is again sent to the liver. There it is converted into glucose. It, in turn, again enters the muscles, or is converted into glycogen.
The entire cycle described is called the Corey cycle. This is a kind of set of enzymatic biochemical processes, during which lactate is transported from the muscles to the liver and then converted into glucose.
Substrates
When discussing the specifics of the regulation of glycolysis and gluconeogenesis, this topic should also be touched upon. Substrates are reagents that form a nutrient medium. In the case of gluconeogenesis, their role is played by:
- Pyruvic acid (PVC). Without it, carbohydrate digestion and amino acid metabolism are impossible.
- Glycerin. It has a strong dehydrating property.
- Lactic acid. It is the most important participant in regulatory metabolic processes.
- Amino acids. They are the main building material of any living organism, including the human one.
The inclusion of these elements in the process of gluconeogenesis depends on the physiological state of the body.
Process steps
They, in fact, completely repeat the stages of glycolysis (glucose oxidation), but only in the opposite direction. Catalysis is carried out by the same enzymes.
There are four exceptions - the conversion of pyruvate to oxaloacetate, glucose-6-phosphate to pure glucose, fructose-1, 6-diphosphate to fructose-6-phosphate, and oxaloacetate to phosphoenolpyruvate.
I would like to make a reservation that both processes are reciprocally regulated. That is, if the cell is sufficiently supplied with energy, then glycolysis stops. What happens after that? Gluconeogenesis kicks in! The same is true in the opposite direction. When glycolysis is activated, gluconeogenesis in the liver and kidneys stops.
Regulation
Another important nuance of the topic under consideration. What can be said about the regulation of gluconeogenesis? If it happened at the same time as glycolysis at a high rate, then the result would be a huge increase in ATP consumption, and heat would begin to form.
These processes are interconnected. If, for example, the flow of glucose through glycolysis increases, then the amount of pyruvate through gluconeogenesis decreases.
Separately, we need to talk about glucose-6-phosphate. This element, by the way, has another name. It is also called phosphorylated glucose. In all cells, this substance is formed during the hexokinase reaction, and inliver - during phosphorolysis. It can also appear as a result of GNG (in the small intestine, muscles) or as a result of the unification of monosaccharides (liver).
How is glucose-6-phosphate used? First, glycogen is synthesized. Then it is oxidized twice: the first time under anaerobic or aerobic conditions, and the second time in the pentose phosphate pathway. And after that it turns directly into glucose.
Role in the body
The function of gluconeogenesis needs to be discussed separately. As everyone knows, in the human body during starvation, nutrient reserves are actively used. These include fatty acids and glycogen. These substances are broken down into non-carbohydrate compounds, keto acids and amino acids.
Most of these compounds are not excreted from the body. Recycling is in progress. These substances are transported by the blood from other tissues to the liver, and then used in the process of gluconeogenesis to synthesize glucose. And she is a key source of energy.
What is the conclusion? The function of gluconeogenesis is to maintain normal glucose levels in the body during intense exercise and prolonged fasting. A constant supply of this substance is necessary for erythrocytes and nervous tissue. If suddenly the body's reserves are depleted, then gluconeogenesis will help out. After all, this process is the main supplier of energy substrates.
Alcohol and gluconeogenesis
This combination must be given attention, since the topic is being studied from a medical andbiological point of view.
If a person consumes a large amount of alcohol, then gluconeogenesis occurring in the liver is greatly slowed down. The result is a decrease in blood glucose. This condition is called hypoglycemia.
Drinking alcohol on an empty stomach, or after heavy physical exertion, can provoke a decrease in glucose levels up to 30% of the norm.
Of course, this condition will negatively affect brain function. It is very dangerous, especially for those areas that keep body temperature under control. Indeed, due to hypoglycemia, they can drop by 2 ° C or more, and this is a very serious dynamic. But if a person in this state is given a solution of glucose, then the temperature will quickly return to normal.
Fasting
Approximately 6 hours after it starts, gluconeogenesis begins to be stimulated by glucagon (a single-chain polypeptide that is 29 amino acid residues).
But this process becomes active only at the 32nd hour. Just at this moment, cortisol (catabolic steroid) is connected to it. After that, muscle proteins and other tissues begin to break down. They are converted into amino acids, which are precursors of glucose in the process of gluconeogenesis. This is muscle atrophy. For the body, it is a forced measure that it has to take in order for the brain to receive a certain portion of glucose necessary for functioning. That is why it is very important that sick people recovering from operationsand disease, received good supplementary nutrition. If this is not the case, then the muscles and tissues will begin to deplete.
Clinical significance
Above, we briefly talked about the reactions of gluconeogenesis and other features of this process. Finally, it is worth discussing the clinical significance.
If the use of lactate as a substrate necessary for gluconeogenesis decreases, there will be consequences: a decrease in blood pH and the subsequent development of lactic acidosis. This can happen due to a defect in the enzymes of gluconeogenesis.
It should be noted that short-term lactic acidosis can also overcome he althy people. This happens under the condition of intensive muscular work. But then this condition is quickly compensated by hyperventilation of the lungs and the removal of carbon dioxide from the body.
By the way, ethanol also affects gluconeogenesis. Its catabolism is fraught with an increase in the amount of NADH, and this is reflected in the balance in the lactate dehydrogenase reaction. It simply shifts towards the formation of lactate. It also reduces the formation of pyruvate. The result is a slowdown in the entire process of gluconeogenesis.
