Flashcards in Gluconeogenesis Deck (23):
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