Gluconeogenesis Pathway, Enzymes & Reactions

The gluconeogenesis is a metabolic pathway that highlights the synthesis of glucose or glycogen from substances which having no composition of carbohydrates. It is the efficient method that produces the energy giving fuel ’ glucose’ from substances comparatively other than carbohydrates, which are stored in the body, and utilize whenever the carbohydrate substrates are not enough available as in starvation or after being of high demand as in intensive physical exertion.

Gluconeogenesis Pathway:

Generally, the biochemical term Gluconeogenesis is the reversal of Glycolysis that is the process of splitting of glucose to produce sufficient energy. Glycolysis progresses to another energy cycle known as “Citric acid cycle” by forming a bulk of substance called pyruvate. So, it is just the reversal of Glycolysis starting with pyruvate.

The substrates gradually turned to pyruvate or other intermediates of the Citric acid cycle by various biochemical reactions from which Gluconeogenesis process starts. Which way does the process proceed if all the working enzymes are same for both glucose synthesis and breakdown? This conflict is overwhelming by the 3 prominent steps in Gluconeogenesis which do not occur with enzymes of Glycolysis. So these 3 steps are sidestep by another set of enzymes to produce glucose at the last.

gluconeogenesis pathway

Glucogenic amino acids:

Glucogenic amino acid engages in transamination which results in a change in the carbon skeleton and directly gets turned to pyruvate. However, few  Glucogenic amino acids turn into the shape of oxaloacetic acid or other intermediates of the Citric acid cycle. On the another side, alanine is preferred in liver and glutamine is preferred in the kidney.


Muscular workout and anaerobic glycolysis in red blood cells generate an enormous amount of lactate. This lactate is utilized by the liver and gets turned to pyruvate by the enzyme lactate dehydrogenase. Pyruvate then further gets converted to glucose by hepatic Gluconeogenesis which is lastly thrown onto muscles for reuse. This all known by the scientific name of Cori cycle.


Glycerol is produced by breaking down of triacylglycerol in the fatty tissue. It is then take up the liver where it changes to pyruvate and enters Gluconeogenesis.

Gluconeogenesis steps:

  1. Gluconeogenesis goes ahead either in mitochondria or cytoplasm via a series of enzymatically catalyzed steps. All the biochemical steps of Gluconeogenesis are the same as that of glycolysis as well the same enzymes excluding in 3 steps that we discussed above.
  2. Glucose is changed to glucose 6 phosphate by glucokinase/ hexokinase in glycolysis, that is totally reversed by glucose 6 phosphatase.
  3. Fructose 1 phosphate is turned to fructose 6 phosphate in glycolysis by phosphorfructokinase which is opposite by fructose 1, 6 bisphosphatase.
  4. Pyruvate is changed to mass phosphoenol pyruvate by pyruvate kinase in glycolysis and is inverse by pyruvate carboxylase and Phosphoenol pyruvate carboxy kinase.
  5. Further steps of Glycolysis in the reverse direction towards glucose utilizing the identical enzymes.

Gluconeogenesis diabetes:

It is completely reversed process of glycolysis, both are regulated reciprocally. The conditions which boost the rate of Glycolysis will decrease Gluconeogenesis and vice versa. This regulation is required to balance the sugar level which will be either minimum or maximum in an unregulated condition or diabetes.

Gluconeogenesis occurs in the liver due to the action of:

The pancreas as produces two significant hormones: insulin and glucagon. Insulin is produced by the pancreas when the glucose levels comparatively high nearby cells. The insulin is the key that opens the door to the cells so that the glucose proceeds into the cells and able to perform the necessary functions to keep the body efficient.

The liver absorbs any insufficient glucose, that the cells cannot use right away and stores it as in the form of glycogen. When the cells require the glucose, then the pancreas will produce the sufficient amount of glucagon, to signal the liver to change the glycogen into glucose for the cells to use it once more time. This is usually between meals when you don’t eat for a long time.

If the liver is no more able to convert glycogen into glucose, it will take up the carbohydrates, fats, and proteins and re-start to convert them into glucose according to the cells requirement. This is the whole process is Gluconeogenesis. This would happen only if there was no glycogen left to use.

Gluconeogenesis enzymes involved:

  • Phosphoglucoisomerase
  • Enolase
  • Phosphoglycerate mutase
  • Phosphoglycerate kinase
  • G3P dehydrogenase
  • Triosephosphate isomerase
  • Fructose 1,6 bisphosphate aldolase
  • Pyruvate carboxylase
  • Phosphoenol pyruvate carboxykinase
  • Fructose 1,6 bisphosphatase
  • Glucose 6 phosphatase

Difference between glycogenesis and glycogenolysis:


Glycogenesis is the formation of glycogen from an aid of glucose. Glycogen is synthesized based on the requirement for glucose and ATP (energy). If both are accessible in huge quantity, then the insufficient amount of insulin forces and the glucose once again convert back into glycogen in liver and muscle cells for the unregulated condition.


Glycogenolysis is the breakdown of glycogen to glucose and it takes place within the muscle cells and liver tissues due to a couple of hormones (peptide and epinephrine). If we go in deep, glycogenolysis having a significant part in the fight-flight responses as well in the balancing of glucose levels in the human blood.

Organs of Gluconeogenesis:

The major organs responsible of synthesizing glucose are liver and kidney. Only they have the require gluconeogenic enzymes to release glucose into circulation. It takes place in the small intestine to a small extent in the fasting state.

Hepatic Gluconeogenesis:

As the liver (the most prolong part of the body) is the major site of Gluconeogenesis. During the very first few hours of fasting, the glycogen reserve gets depleted dramatically and Gluconeogenesis boosts by its regulatory mechanism as mentioned above. Liver primarily utilizes lactate, alanine, and glycerol. Lactate gets finally changed to pyruvate by Cori cycle and then underwhelm Gluconeogenesis in liver. Alanine gets turned to glucose by Alanine cycle. Furthermore, acetyl coA is predominantly released in the liver which more increases Gluconeogenesis Hepatic Gluconeogenesis decreases in condition causing acidosis.

Hi, This is Hamza Khan from Peshawar, Pakistan. I am a 2nd prof MBBS Student at Bannu Medical College and a hobby Blogger. The Purpose of this site is to share my knowledge and Guide new Medical Students.

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