What is gluconeogenesis ?
glucose formation from non carbohydrate precursors
What is the daily requirement for glucose ?
- 160g
- brain uses 120g of this
What is the main site of gluconeogenesis ?
- major site is the liver
- in extreme circumstances can happen in kidneys also
Is gluconeogenesis the reverse of glycolysis ?
NO !!
it is not the reverse of glycolysis
What is the role of gluconeogenesis ?
it helps to maintain blood glucose levels so the muscles and brain can extract it
How does gluconeogenesis happen ?
- precursors are first converted into pyruvate or enter the pathway further along
- pyruvate is converted into glucose
What are the major precursors for gluconeogenesis ?
- lactate
- amino acids
- glycerol
Where is lactate produced ?
- lactate is produced in skeletal muscles
- produced when glycolysis exceeds oxidative metabolism
Which amino acids are not precursors for gluconeogenesis ?
- leucine
- lysine
Where is glycerol found ?
- found in fat cells
- triglycerides are hydrolysed into glycerol and fatty acids
- glycerol is hydrophilic and so it can be transported to the liver and converted to glucose
- fatty acids can’t b converted into glucose
Describe difference between glycolysis and gluconeogenesis
glycolysis : glucose to pyruvate
yields 2 ATP and 2 NADH
gluconeogenesis : pyruvate to glucose
requires 6 ATP and 2 NADH
Which 3 steps of glycolysis are irreversible ?
- hexokinase
- phosphofructokinase
- pyruvate kinase
What happens to these steps in gluconeogenesis ?
these 3 steps must be bypassed in gluconeogenesis
What is the first bypass that happens in gluconeogenesis ?
- pyruvate is converted into phosphoenol-pyruvate
- this is a 2 step process :
1) pyruvate is carboxylated to oxaloacetate by pyruvate carboxylase and this requires energy from ATP
2) oxaloacetate is decarboxylated and phosphorylated to phosphoenol-pyruvate by phosphoenolpyruvate carboxykinase and this requires GTP
Where is the phosphoenolpyruvate carboxykinase enzyme located ?
it is located in both the cytosol and mitochondria
When is mitochondrial phosphoenolpyruvate used ?
- it is used if lactate is the glucogenic precursor
- lactate to pyruvate yields NADH
- the NADH generated in the cytosol is used further up in the pathway
When is cytosolic phosphoenolpyruvate used ?
- it is used if pyruvate is the glucogenic precursor
- used if NADH is needed
Describe the oxaloacetate shuttle
- oxaloacetate cannot directly diffuse out the mitochondria
- it is converted to malate which leaves via a specific transporter
- NADH is oxidised to NAD+ in the mitochondria
- malate is converted back to oxaloacetate by malate dehydrogenase in the cytosol
- NAD+ is reduced to NADH in the cytosol
- oxaloacetate can then be converted to phosphoenol-pyruvate
Describe how lactate is converted into pyruvate
- lactate is converted into pyruvate via lactate dehydrogenase and this yields NADH
- this takes place in the cytosol
What is the overall reaction of bypass 1 ?
pyruvate + ATP + GTP + H2O > PEP + ADP + GDP + 2H+ + Pi
What happens between bypass 1 and bypass 2 ?
glycolytic enzymes will work in reverse
What is the second bypass that happens in gluconeogenesis ?
fructose 1,6 - bisphosphate is converted to fructose 6 - phosphate by the enzyme fructose 1,6 - bisphosphatase
fructose 1,6 - bisphosphate + H2O > fructose 6 - phosphate + Pi
What is the third bypass that happens in gluconeogenesis ?
glucose 6 - phosphate is converted to glucose by glucose 6 - phosphatase
- this happens in the endoplasmic reticulum
- this enzyme is only found in the liver and kidney
Explain why the brain and skeletal muscles lack the glucose 6 - phosphatase enzyme
- the brain doesn’t want to turn glucose 6 - phosphate into glucose which can then enter the bloodstream because it is very reliant on glucose
- in muscles glucose is used for the fight or flight response
