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Flashcards in Gluconeogenesis Deck (23):

Define 'gluconeogenesis'

a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids


In which tissues is gluconeogenesis active?

In the liver, but during prolonged starvation it can also occur in the kidney cortex (but production of pyruvate and lactate can occur in muscle)


Under what circumstances will gluconeogenesis occur?

During prolonged exercise or starvation where the glycogen reserves only last for between 12-24 hours, thereafter gluconeogenesis is required to maintain blood glucose levels within safe limits.


What are the major precursors for gluconeogenesis (including their tissue origin)?

Glycerol (from triacylglycerol hydrolysis in adipose tissue), lactate (from anaerobic respiration in erythrocytes and active skeletal muscle) and amino acids (from breakdown of muscle protein)


In which part(s) of the cell does gluconeogenesis occur?

Cell cytosol, except for the carboxylation of pyruvate, which occurs in the mitochondria.


Which 3 enzymes catalyse irreversible reactions in glycolysis?

hexokinase, phosphofructokinase-1 (PFK-1) and pyruvate kinase


Outline the process of gluconeogenesis, naming the compounds involved

Pyruvate (lactate and amino acids may contribute) -> oxaloacetate -> malate (malate shuttle transport) -> oxaloacetate -> phosphoenolpyruvate (PEP) -> GAP (or DHAP) -> fructose-1,6-bisphosphate -> fructose-6-phosphate -> glucose-6-phosphate -> glucose


List the enzymes involved in gluconeogenesis

Pyruvate carboxylase, maltate dehydrogenase, PEP-carboxylase, fructose-1,6-bisphosphatase, glucose-6-phosphatase


What's the role of pyruvate carboxylase?

To remove carbon dioxide from pyruvate to form oxaloacetate


What's the role of maltate dehydrogenase?

To function as part of the 'malate shuttle' pathway, which converts oxaloacetate to malate and back to oxaloacetate again


What's the role of PEP-carboxylase?

This enzyme converts oxaloacetate to phosphoenolpyruvate (PEP) by removing a carbon dioxide group and this requires the hydrolysis of GTP -> GDP + Pi to work


What's the role of fructose-1,6-bisphosphatase

Facilitates the removal of a phosphate group from fructose-1,6-bisphosphate to fructose-6-phosphate through hydrolysis


What's the role of glucose-6-phosphatase?

Facilitates the removal of a phosphate group from glucose-6-phosphate to produce glucose through hydrolysis


Why can't fatty acids be used to make glucose?

Fatty acids are broken down to acetyl CoA which cannot be converted to glucose (as it can't form oxaloacetate), only the glycerol can be converted


How does fatty acid oxidation facilitate gluconeogenesis?

Fatty acids provide energy for the process to occur, and the high levels of acetyl CoA activate pyruvate carboxylase , and the acetyl CoA and NADH produced inhibit the PDC so this will redirect respiration to form lactate and then enter gluconeogenesis in muscle cells etc.


What 3 hormones regulate gluconeogenesis?

Insulin, adrenaline, glucagon


Why is a 'malate shuttle' required to transport oxaloacetate?

Oxaloacetate cannot cross the inner mitochondrial membrane so it is reduced to malate, which is transported into the cytosol where it is re-oxidised,


Why is gluconeogenesis excessive in diabetics?

there is an increased supply of precursor molecules e.g. glycerol and amino acids, along with increased levels of fatty acids. In addition, there is an increased glucagon:insulin ratio


Define 'glucogenic amino acids'

If an amino acid can be broken down to produce pyruvate or oxaloacetate (then glucose can be synthesised from the amino acid)


Which two amino acids aren't glucogenic?

leucine and lysine


What are the two main glucogenic amino acids?

Glutamine and alanine


Define the 'cori cycle'

the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolized


Explain the role of the cori cycle in gluconeogenesis

It produces lactate which can then travel to the liver in the blood and therefore be converted to glucose to increase blood glucose levels.