BGM1002/L24 Gluconeogenesis Flashcards
What are normal blood glucose levels?
4-6mmol/L
What 2 hormones are involved in blood glucose homeostasis?
Insulin and glucagon
Why must blood glucose levels be regulated? (3)
Glucose is preferred energy source of brain and CNS
Only fuel source of RBC
Breakdown in blood glucose homeostasis causes problems
What is the only fuel source of RBCs?
Glucose
Define blood glucose homeostasis.
Maintenance of blood sugar levels within narrow physiological limits
What percentage of glucose does the brain use?
75% or 120g
How much glucose is circulating the body at a given time?
20g
How much glucose is readily available as glycogen at any given time?
190g
How long would stored glucose last in the body?
1 day
When does hypoglycaemia occur? (3)
Starvation
Insulin overdose
During and after exercise
What results from hyperglycaemia? (3)
Low glucose levels inside cells
Hyperosmolar hyperglycaemic state
Long-term complications
When does hyperglycaemia occur? (2)
Post-prandial (meal)
Inadequate insulin administration
When is gluconeogenesis initiated?
2 hours post-prandially
Give an advantage of gluconeogenesis.
Preserves glycogen for emergencies
What is the maximum period that gluconeogenesis occurs for?
8-12 hours
Where does gluconeogenesis occur?
High-intensity exercise principally in liver
Name 3 sources for gluconeogenesis.
Pyruvate/lactate
Glycerol
Citric acid cycle intermediates
Amino acids
When is lactate produced in cells? (2)
When pyruvate is not needed for Krebs cycle
When pyruvate cannot be fed into the cycle due to lack of oxygen
What organ is responsible for most lactate production?
Skeletal muscle
Why must lactate be transported to the liver?
It cannot be used for anything else
It is converted to glucose to be (re)used
What can pyruvate be converted into in skeletal muscle?
Alanine
How many pyruvate molecules are used to create a glucose molecule?
2
Name 3 energy unfavourable reactions in glycolysis that must be overcome in gluconeogenesis.
Pyruvate -> PEP
F-1,6-bisphosphate -> F-6-P
G-6-P -> Glucose
What is step 1 in gluconeogenesis?
Pyruvate -> phosphoenolpyruvate
Name the intermediates in step 1 of gluconeogenesis.
Pyruvate -> oxaloacetate
Oxaloacetate -> malate
What enzyme converts pyruvate to oxaloacetate?
Pyruvate carboxylase
What enzyme converts oxaloacetate to PEP?
PEP carboxykinase
Why must oxaloacetate be converted to malate in step 1 of gluconeogenesis?
To exit mitochondria
Name any additional molecules required to convert pyruvate to oxaloacetate.
CO2 + Biotin + ATP -> Biotin + ADP + Pi
Name any additional molecules required to convert oxaloacetate to PEP.
GTP -> GDP + CO2
What is step 2 of gluconeogenesis?
Fructose-1,6-bisphosphate -> Fructose-6-phosphate
What enzyme is required to convert F-1,6-phosphate to F-6-phosphate?
Fructose-1,6-bisphosphatase
What additional molecules are required in step 2 of gluconeogenesis?
H2O -> Pi
Name step 3 of gluconeogenesis.
Glucose-6-phosphate -> glucose
What enzyme is required for step 3 of gluconeogenesis?
Glucose-6-phosphatase
What additional molecules are required for step 3 of gluconeogenesis?
H2O -> Pi
What is the net cost of gluconeogenesis in the form of ATP and GTP?
4ATP and 2 GTP
Where does the ATP for gluconeogenesis come from?
Lipid oxidation
Amino acid catabolism
What are the effects of overexpression of phosphoenolpyruvate carboxykinase in mice?
Enhanced exercise capacity (6k vs 0.2k)
Ate 60% more than controls
1/2 body weight and 10% body fat of controls
Increased mitochondria
High triglyceride concentration
Extended lifespan (+2yrs)
What are the effects of a high-protein, carbohydrate-free diet in humans?
42% increase in energy expenditure
Body uses amino acids as pre-cursors for gluconeogenesis
How is gluconeogenesis regulated?
Allosterically of enzymes for irreversible steps in the liver
When is gluconeogenesis activated?
When cells have a surplus of energy
Why do AMP and ADP inhibit gluconeogenesis?
Low energy status
Need to send pyruvate into TCA cycle to get energy
Why do citrate and acetyl CoA activate gluconeogenesis?
Indicate high energy status
Plenty of biosynthetic precursors
Favours converstion of pyruvate into G6P for glycogen synthesis
