Gluconeogenesis and Why It Matters in a Low Carb Diet

The Definition of Gluconeogenesis and Its Low Carb Connection

Glucose sugar molecule
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Gluconeogenesis is the process of synthesizing glucose in the body from non-carbohydrate sources such as lactate and pyruvate. It is the biosynthesis of new glucose, not from  Gluconeogenesis can be seen as the reverse anabolic process of glycolysis, the breakdown and extraction of energy from glucose.

Gluceoneogenesis: Normal Diet vs. Low Carb Diet 

All our body's cells can use glucose, and a few are dependent on it.

If you were consuming a normal diet,  your body gets plenty of glucose from the average American diet food you consume. For example, starches (plentiful in grains including flour, potatoes, etc.) are essentially long chains of glucose. In addition, naturally-occurring sugars such as added sugars are plentiful in the diets of most people. However, if carbohydrate is not being consumed, the body will make glucose from other sources. Though the process uses excess energy and is literally the reverse process of how the body normally get energy, gluceoneogenesis is a work-around for your body's metabolism to get and maintain the energy it needs to conduct normal bodily functions.

Gluconeogenesis and Your Liver

The process of gluconeogenesis takes place primarily in the liver, where glucose is made from amino acids (protein), glycerol (the backbone of triglycerides, the primary fat storage molecule), and glucose metabolism intermediaries like lactate and pyruvate.

Lactate is produced by a breakdown of muscle tissue and sent to the liver through the bloodstream. At night, when we haven't eaten for several hours, the body begins to manufacture glucose using gluconeogenesis. Here's how the process works.

The Three Steps in Gluconeogenesis

  • The conversion of pyruvate to phosphoenolpyruvic acid (PEP) is the first step in gluconeogenesis. There are several steps required In order to convert pyruvate to PEP including specific enzymes. For example, pyruvate carboxylase, PEP carboxykinase and malate dehydrogenase are responsible for this conversion. Pyruvate carboxylase is found on the mitochondria and converts pyruvate into oxaloacetate. Oxaloacetate cannot pass through the mitochondria membranes, so it must be first converted into malate by malate dehydrogenase. Malate can then cross the mitochondria membrane into the cytoplasm where it is then converted back into oxaloacetate with another malate dehydrogenase. Lastly, oxaloacetate is converted into PEP via PEP carboxykinase. The next several steps are exactly the same as glycolysis only the process is in reverse.
  • The second step that differs from glycolysis is the conversion of fructose-1,6-bP to fructose-6-P with the use of the enzyme fructose-1,6-phosphatase. The conversion of fructose-6-P to glucose-6-P uses the same enzyme as glycolysis, phosphoglucoisomerase.
  • The last step that differs from glycolysis is the conversion of glucose-6-P to glucose with the enzyme glucose-6-phosphatase. This enzyme is located in the endoplasmic reticulum.

The Importance of Glucose to Your Body and Your Brain

Glucose is the major source of energy for the body and the brain. Gluconeogenesis ensures that in the absence of glucose from glycolysis that critical limits of glucose are maintained when carbohydrate is absent. The brain alone uses as much as 100 grams of glucose a day. The body is able to quickly use glucose for energy. 


Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients) (2005), Institute of Medicine, Food and Nutrition Board, National Academy of Sciences.

The Medical Biochemistry January 2016.

UC Davis. Gluconeogenesis. ChemWiki 2016.

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