GlucoNEOgénesis: síntesis de glucosa a partir de piruvato, lactato, glicerol y aminoácidos

Introduction to Gluconeogenesis

In this section, we will discuss what gluconeogenesis is and the substrates used to form glucose. Gluconeogenesis is responsible for supplying the body with glucose during prolonged fasting and vigorous exercise.

What is Gluconeogenesis?

• Gluconeogenesis is the formation of glucose from non-carbohydrate substrates.

• Substrates for gluconeogenesis include pyruvate, lactate, glycerol, and certain amino acids.

• Amino acids that serve as substrates for gluconeogenesis are called glucogenic amino acids.

Enzymatic Steps of Gluconeogenesis

• Gluconeogenesis involves a series of enzymatic reactions that convert pyruvate back into glucose.

• Unlike glycolysis, which has irreversible reactions, gluconeogenesis has unique enzymes capable of reversing those irreversible reactions.

• Pyruvate as a substrate for gluconeogenesis needs to enter the mitochondria first because it cannot be converted to phosphoenolpyruvate (PEP) by the enzyme pyruvate kinase in glycolysis.

Connection with Krebs Cycle

• Once inside the mitochondria, pyruvate is converted to oxaloacetate by the enzyme pyruvate carboxylase.

• Bicarbonate provides carbon dioxide for this reaction, requiring ATP and biotin as coenzymes.

• Oxaloacetate then converts to malate through malate dehydrogenase before being exported out of the mitochondria into the cytosol.

Conversion to Phosphoenolpyruvate (PEP)

• In the cytosol, malate is converted back to oxaloacetate and then further converted to PEP through a series of reactions involving ATP and NADH.

• PEP is then converted to fructose-1,6-bisphosphate and eventually to glucose through a series of reversible reactions.

Limiting Steps in Gluconeogenesis

• The conversion of fructose-1,6-bisphosphate to fructose-6-phosphate requires the enzyme fructose-1,6-bisphosphatase.

• The final step in gluconeogenesis is the conversion of glucose-6-phosphate to free glucose, which requires the enzyme glucose-6-phosphatase.

Gluconeogenesis from Lactate

In this section, we will explore how lactate serves as a substrate for gluconeogenesis. Lactate is produced in skeletal muscles during vigorous exercise and also by erythrocytes due to their lack of mitochondria.

Conversion of Lactate to Pyruvate

• In the liver, lactate is converted back into pyruvate by the enzyme lactate dehydrogenase.

• This conversion requires NADH as a reducing agent.

Pyruvate Conversion and Glucose Formation

• Pyruvate follows the same sequence as discussed earlier, entering the mitochondria and converting to oxaloacetate or malate before being exported out.

• Eventually, glucose is formed through a series of enzymatic reactions similar to those in gluconeogenesis from other substrates.

Glycerol as a Substrate for Gluconeogenesis

In this section, we will discuss how glycerol can be used as a substrate for gluconeogenesis during prolonged fasting conditions.

Glycerol Utilization

• During prolonged fasting, triglycerides stored in adipose tissue are broken down into glycerol and fatty acids.

• Glycerol can be converted to glycerol-3-phosphate, which then enters the gluconeogenesis pathway.

• Glycerol-3-phosphate is converted to dihydroxyacetone phosphate (DHAP) and eventually to glucose through a series of enzymatic reactions.

Conclusion

Gluconeogenesis is the process by which glucose is formed from non-carbohydrate substrates such as pyruvate, lactate, glycerol, and certain amino acids. It involves a series of enzymatic steps that reverse some of the irreversible reactions in glycolysis. Lactate and glycerol can serve as substrates for gluconeogenesis during prolonged fasting or vigorous exercise. Understanding these processes helps us comprehend how the body maintains glucose levels in various metabolic conditions.

New Section

This section discusses the role of glycerol kinase and glycerol 3-phosphate dehydrogenase in the conversion of glycerol to dihydroxyacetone phosphate, which is then converted to fructose 1,6-bisphosphate. It also mentions how amino acids can be substrates for gluconeogenesis during prolonged fasting.

Glycerol Metabolism

• Glycerol kinase and glycerol 3-phosphate dehydrogenase are enzymes involved in the conversion of glycerol to dihydroxyacetone phosphate.

• ATP is required for this reaction.

• Dihydroxyacetone phosphate can quickly convert to glyceraldehyde 3-phosphate through subsequent reactions.

• Glyceraldehyde 3-phosphate further undergoes steps leading to the formation of free glucose.

Amino Acids as Substrates for Gluconeogenesis

• During protein degradation, amino acids are released.

• Some amino acids, like alanine, can be considered glucogenic because they can be converted into pyruvate and enter gluconeogenesis.

• Other amino acids, such as methionine and valine, may not necessarily convert into pyruvate but can become intermediates in the Krebs cycle.

• Aspartate can enter the Krebs cycle as oxaloacetate or acetate via transamination reactions.

• Glucose synthesis from these substrates allows for glucose production during fasting.

Glucose Transport

• Glucose needs to move from intracellular space to extracellular space in tissues like liver and kidneys.

• Transporters called GLUT (glucose transporter) facilitate this movement.

• Liver cells have GLUT2 transporters, while kidney cells have GLUT3 transporters.

• Glucose is transported from intracellular to extracellular space, making it available for tissues that require it.

The transcript provided was in a language other than English. The summary has been translated into English for clarity and understanding.