Metabolism Flashcards
What are the regulatory steps in glycolysis
- The phosphorylation of glucose in the muscle and brain by hexokinase (glucokinase in the liver) traps glucose in the cell which maintains the concentration gradient across the plasma membrane and commits glucose to the glycolysis pathway
- Phosphofructokinase catalyses the conversion of Fructose-6P to fructose-1,6BP. This is the rate-limiting step of glycolysis and is irreversible.
- Pyruvate kinase catalysis the final step in glycolysis from PEP to pyruvate.
Explain the role of the Cori cycle
The Cori cycle converts lactate produced in muscles respiring anaerobically to glucose.
In intense muscle activity anaerobic glycolysis dominates. Lactate diffueses out of the cell and is transported to the liver via the blood where is is oxidised to pyruvate, which can then be converted back to glucose. This is returned to the muscles.
This reduces the levels of lactate in muscle and provides more glucose for respiration. This process is not energetically favourable beacuase the muscle gains 2ATP from glycolysis but 6ATP are used in the liver to produce glucose
What are the metabolic signals of the fed state?
Increased insulin secretion in response to raised blood glucose
Increased glycogen synthesis
Increased TAG and protein synthesis
What are the metabolic signals of the fasted state?
Low insulin:glucagon ratio
Increase in free fatty acids as TAG are broken down
Reduced levels of glycogen in the muscle
What are the metabolic signals of the starved state?
Reduction in glucose levels
Depletion of glycogen stores in the muscle and liver
Increase in ketones as FFA are converted in the lvier
Describe the role of the liver in regulating blood glucose
In the fed state, when glucose levels are high. Excess blood glucose is transported into hepatocytes via GLUT2 and trapped in the liver by the action of hexokinase and glucokinase (glucose to Glucose-6P). Glucose-6P is then converted to glucose-1P and then UDP-glucose which is the substrate used to create branched glycogen polymers.
In the fasting state glycogen stores in the liver are broken down into glucose and released into the blood. Glucagon promotes lipolysis in liver cells, increasing FFA which can be metabolised by beta oxidation.
In the starved state the liver converts free fatty acids into ketones which can be used as an energy source and produces glucose by gluconeogenesis.
Describe the changes in blood glucose levels following a meal
Increase in plasma glucose causes B-cells in
The islets of Langerhans to secrete insulin
(insulin to glucagon ratio favours insulin)
Glycogen synthesis, TAG synthesis and protein
synthesis are stimulated in the tissues
(anabolism)
Glucose is used by the brain as the sole
energy source and uptake is not dependent
on insulin
Muscle and adipose take up and use glucose
but uptake is insulin dependent.
Describe the metabolic changes that occur in the fasted state to increase glucose levels
Blood glucose levels fall, insulin secretion stopped
Insulin to glucagon ratio favours glucagon
as insulin levels in the blood fall
Liver glycogen is broken down to
maintain blood glucose promoted by glucagon
TAG are hydrolysed in adipose releasing FFAs
Muscle uses up stored muscle glycogen
Describe the metabolic changes that occur in the starved state
Noradrenaline and cortisol levels increase which
activates protein breakdown in muscle releasing
alanine and glutamate
NorA promotes more TAG breakdown and glycerol
release from adipose (rich in sympathetic nerves)
Alanine + glycerol etc are gluconeogenic and liver
uses these to maintain blood glucose
FFA are converted to ketones by the liver
which can be used by the brain
and muscle as an energy source
Functions of insulin
Anabolic effects. Promotes synthesis and energy storage
Increase liver glycogen synthesis
Increases glycolysis
Increase glucose uptake in peripheral tissues
Increase amino acid uptake and protein synthesis
Inhibits protein breakdown
Increases lipogenesis
Inhibits lipolysis
Functions of glucagon
Catabolic functions, releases glucose inhibits synthesis
Stimulates glycogen breakdown
Stimulates gluconeogenesis
Stimulates protein breakdown
Inhibits lipogenesis
Activates lipolysis and ketone synthesis
How does the kinetic activity of hexokinase and glucokinase relate to their functions?
hexokinase enzymes are found in all tissue types while glucokinase is found in the liver.
hexokinase and glucokinase both phosphorylate glucose to glucose-6P, thereby trapping it within the cell which feeds into the glycolysis pathway and maintains the glucose concentration gradient.
hexokinase has a high affinity for glucose, (Km=0.05mM) which means that even if the intracellular concentration of glucose is low, the reaction can still proceed so cells can produce ATP.
At physiological concentrations of glucose (5mM), the hexokinase enzyme is working at Vmax and is relatevely insensitive to changes in blood glucose over this level. High levels of glucose-6P inhibit hexokinase
Glucokinase has a lower affinity for glucose (Km=10mM) which enables the liver to respond to high levels of glucose in the blood and unlike hexokinase is not inhibited by glucose-6P. Excess glucose taken up by the liver is converted into Glucose-1P and stored as glycogen.
What is the key step in the gluconeogenesis pathway?
Carboxylation of pyruvate to oxaloactetate (requires biotin as a co-factor)
Oxaloacetate is then converted to phosphoenolpyruvate
4 key molecules derived from tyrosine
Dopamine
Epinephrine
Melanin
thyroxine
What is the effect of growth hormone on metabolism?
Increases protein synthesis
Increases fatty acid metabolism
Anti-insulin effect in muscle
Net result is to increase body protein
