Summary 13032021

Gluconeogenesis

It happens after long periods of fasting once the glycogen reservoirs have been consumed.

Glucose is synthetized from precursors.

Its goal is to keep blood glucose levels stable.

It can contribute to hyperglycemia in diabetic patients.

It turns non-carbohydrate substrates into glucose.

Lactate

Amino acids

Glycerol

From lactate

Participants listed like:

Substrate

Enzymes

Products

Lactate

Irreversible steps of glycolysis must be replaced.

Lactate dehydrogenase

Pyruvate

Pyruvate

Pyruvate carboxylase

Oxaloacetate

This step is done in the mitochondria.

It uses biotin and ATP.

Glucokinase

Phosphofructokinase 1

Pyruvate kinase

Oxaloacetate

Malate dehydrogenase

This enzyme acts in the citric acid cycle. It reduces oxaloacetate.

This step also happens in the mitochondria.

Malate

Malate

It can exit the mitochondria but must be turned back to oxaloacetate in the cytosol.

Malate dehydrogenase

Oxaloacetate

Oxaloacetate

Phosphoenolpyruvate carboxykinase

By decarboxylation. It uses GTP.

Phosphoenolpyruvate

Afterwards it follows the steps of glycolysis in reverse until it reaches the next irreversible reaction catalyzed by phosphofructokinase 1.

Fructose 1,6-bisphosphate

Fructose 1,6-bisphosphatase

By hydrolysis without ATP production.

Fructose-6-phosphate

The reactions happen like this:

Afterwards it follows the steps of glycolysis in reverse until it reaches the next irreversible reaction catalyzed by Glucokinase.

Glucose-6-phosphate

Glucose-6-phosphatase

By hydrolysis without ATP production.

Glucose

It is released into the blood.

From amino acids

Carbon skeletons from amino acids can be converted into glucose.

Alanine and glutamine usually. They are exported by muscle for gluconeogenesis.

Alanine

Alanine aminotransferase

Pyruvate

Afterwards it follows the steps of glycolysis in reverse replacing irreversible steps like it was described for lactate.

Other amino acids

They are converted into citric acid cycle intermediates until they become malate for gluconeogenesis.

Aspartate

Aspartate aminotransferase

Oxaloacetate

Glutamate

Alpha ketoglutarate

Glutamate dehydrogenase

Others are converted to alanine and different citric acid cycle intermediates.

Amino groups are turned to urea and excreted in urine.

From glycerol

It enters the process as Glycerol-3-phophate.

Glycerol

Glycerol kinase

Glycerol-3-phosphate

It uses 2 ATP.

It uses ATP and GTP.

Regulation

It takes place in the liver.

Glucagon

Insulin and glucagon are the most important.

It stimulates gluconeogenesis. It increases during fasting.

Insulin

This hormone inhibits gluconeogenesis. It increases in fed state.

Biochemistry I

Paola Pimiento

References

Baynes, W. & Dominiczak, M. (2014). Medical Biochemistry (4th ed.). Elsevier.

Zhang, X., Yang, S., Chen, J., & Su, Z. (2019). Unraveling the Regulation of Hepatic Gluconeogenesis. Frontiers in endocrinology, 9, 802.

Their levels change in fed and fasting states.

It also regulates glucose transport, lipid synthesis and glycogen synthesis.

This hormone's function is to prevent hypoglycemia.

By suppressing gluconeogenic genes expression.

Some of its enzymes are regulated.

Fructose 1,6-bisphosphatate.

It is inhibited by Fructose 2,6-bisphosphate presence.

Fructose 2,6-bisphosphate is a product of Phosphofructokinase 2/Fructose 2,6-bisphosphatase action.

It stimulates Phosphofructokinase 1 and glycolysis.

Glucocorticoid

This sterol hormone stimulates gluconeogenesis.