What Is Gluconeogenesis?


Now it’s time to answer the question, what is gluconeogenesis? But first, it is important to understand some background information about your body’s fat-burning process:

Eating fat burns fat. Eating carbohydrates burns carbohydrates. It’s that simple, right? Yes and no. There’s more to it than that.

Your body has many different metabolic pathways it uses to provide energy to your cells. Glycolysis (using sugar as fuel) and lipolysis (using fat as fuel through beta-oxidation) are the best known metabolic pathways, but there are many others. One pathway in particular converts amino acids from proteins into fuel.

Why does it matter? Because it may be a factor that prevents you from going into ketosis and losing fat when you are on a ketogenic diet.

Gluconeogenesis Definition

Gluconeogenesis is the formation of new glucose molecules in the body, rather than the breakdown of glucose from long-stored molecules of glycogen. It occurs primarily in the liver, although it can also occur in small amounts in the kidneys and small intestine. Gluconeogenesis is the opposite process to glycolysis, which is the breakdown of glucose molecules into their components.

Gluconeogenesis Functions

The human system creates glucose to keep blood glucose levels under control. Because cells use glucose to create the energy component adenosine triphosphate, blood glucose levels (ATP) must be maintained. Gluconeogenesis occurs when a person has not eaten for a period of time, such as during a crisis or starvation.

Since the body does not have enough carbohydrates from food to break down into glucose during this time, it must rely on other molecules for gluconeogenesis, such as amino acids, lactate, pyruvate and glycerol. After glucose is produced in the liver through glycation, it is released into the bloodstream where it can be used as energy by cells in other areas of the body.

Because it requires energy input, gluconeogenesis is also known as endogenous glucose production (EGP). Because gluconeogenesis is the opposite of glycolysis, which releases large amounts of energy, it can be predicted that gluconeogenesis requires a large energy input. However, since gluconeogenesis occurs when the body is already depleted of energy, it requires workarounds to conserve energy.

Gluconeogenesis and glycogenolysis have the same purpose. However, they are used in different ways. Gluconeogenesis is usually used during shorter fasts, such as when a person’s blood sugar drops between meals or after a good night’s sleep, but gluconeogenesis is more often used during longer fasts. However, both processes occur to some extent in the body because glucose is needed for energy production.

Gluconeogenesis Pathway

  1. Gluconeogenesis begins in the mitochondria or cytoplasm of the liver or kidney. First, two pyruvate molecules are carboxylated to form oxaloacetate. For this an ATP (energy) molecule is required.
  2. Oxaloacetate is reduced to malate by NADH so that it can be transported out of the mitochondria.
  3. Malate is oxidized back to oxaloacetate once it is out of the mitochondria.
  4. Oxaloacetate forms phosphoenolpyruvate using the enzyme PEPCK.
  5. Phosphoenolpyruvate is changed to fructose-1,6-bisphosphate, which then becomes fructose-6-phosphate. ATP is also used in this process, which is basically reverse glycolysis.
  6. Fructose-6-phosphate is transformed into glucose-6-phosphate by the action of glucose phosphate isomerase.
  7. Glucose is formed from glucose-6-phosphate in the endoplasmic reticulum of the cell via glucose-6-phosphatase. To form glucose, a phosphate group is removed and glucose-6-phosphate and ATP become glucose and ADP.

Importance of Gluconeogenesis

  • During deprivation, the gluconeogenesis cycle is important for blood glucose regulation.
  • Many cells and tissues, including red blood cells, neurons, skeletal muscle, kidney medulla, testes and embryonic tissue, depend on glucose to meet their energy needs.
  • The Neoglucogenesis cycle removes metabolites such as lactate (produced by muscles and RBCs) and glycerol from the bloodstream (produced from adipose tissue).

Is Gluconeogenesis Bad?

During the first three days of the ketogenic diet, stored glycogen and amino acids are the body’s main source of fuel. Initially, however, glycogen is the primary fuel source. Once glycogen is almost completely used up, amino acids from food and muscle become the main source of fuel.

But the body cannot burn amino acids as fuel forever. We need them to perform many other functions that are necessary for our survival.

For example, amino acids help build and repair tissues such as hair, nails, bones, muscles, cartilage, skin and blood. Many enzymes and hormones are also made from amino acids. In other words, long-term use of amino acids for energy is a bad idea.

That’s why the body has two other sources of fuel – fat and ketone bodies – to help maintain health and keep muscle mass. The only problem is that the body doesn’t use them right away.

When does the Body Use Ketogenesis instead of Gluconeogenesis?

To figure out when the body shifts to ketogenesis (the use of ketone bodies as fuel), let’s look at what happens when the body is in a fasted state. In a review of several fasting studies, researchers found that it takes 18 to 24 hours to deplete glycogen stores, and more than 2 days after that for the body to shift into ketosis.

That’s two days without glycogen or ketone bodies as fuel! How does the body fuel itself during this time? Through gluconeogenesis.

In one case study, a healthy 41-year-old man decided to go on a 40-day medically supervised fast. To indirectly measure whether he used amino acids for energy, researchers tracked the amount of nitrogen in his urine.

During his first week of fasting, the man’s total urinary excretion was 10 to 12 grams of nitrogen per day. In the third week, it dropped significantly. According to the researchers, this significant drop in urinary nitrogen levels marked a shift from the man’s primary use of amino acids as fuel to the use of fat and ketone bodies as fuel. This shift took the man more than two days to complete.

However, it’s important to recognize that this is just what happened to a healthy 41-year-old man. Everyone responds differently to fasting and ketogenic diets.

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