Metabolism in fed and starved states Flashcards
Fed state
Described as having a high insulin to glucagon ratio.
- High insulin
- Low glucagon
Fasting state
6-12 hours after a meal
Described as having a low insulin to glucagon ratio
- Low insulin
- High glucagon.
Liver in the fed state
- Glucose
- Lactate
- Glycerol
- Triglycerides
- GLUT
High insulin to glucagon ratio: 0.5
Glucose is high in concentration, so it enters GLUT-2 channel into the liver.
Hepatocytes store glucose as glycogen and converts to TG and released via VLDL.
Lactate from RBCs and muscle, glycerol from peripheral tissue converted into TGs.
Pyruvate formed from excess amino acids
- metabolised in TCA
- converted to TG
Muscle metabolism in fed state
- Glucose
- Fatty acids
- Amino acids
- GLUT
Glucose enters myocytes via GLUT-4 transporter.
- Converted into glycogen or used for TCA
Fatty acids oxidised to acetyl CoA and metabolised for energy
- FA come from diet via chylomicrons
- FA comes from VLDL from liver.
Amino acids made into proteins
Adipose tissue in fed state
- Glucose
- GLUT
- Fatty acids
- Glycerol
Glucose enters adipocytes via GLUT 4.
- Used for energy through glycolysis and TCA.
- Converted to TG by converting to Acetyl CoA then lipogenesis.
Fatty acids from VLDL and chylomicrons converted to TG.
Glycerol from TGs returned to the liver.
Brain in the fed state.
Glucose is taken into neural tissue via GLUT1 and GLUT3.
- Aerobic respiration to produce ATP.
Liver metabolism in early fasting state.
- Glucose
- Hormones
- Protein
- Fatty acids
- Citrate and acetyl CoA
6-12 hours after eating.
GLUT2 has low affinity for glucose so as plasma glucose falls, liver doesn’t take up glucose.
Glucagon increases cAMP production (activation of glycogen phosphorylase):
- Glycogenolysis and gluconeogenesis are activated.
Protein broken down to release amino acids—-> gluconeogenesis.
Lipolysis: TG hydrolysed to FA and glycerol
- FA used for energy via oxidation
- Citrate and Acetyl CoA inhibit glycolysis and activate gluconeogenesis
What amino acid is used for gluconeogenesis?
Alanine
Adipose tissue metabolism in the early fasting state
- GLUT
- TG
- Glycerol
GLUT 4 dissociates from membrane as insulin has decreased.
- Less glucose is taken in.
- Glucose metabolism is heavily inhibited.
Lipolysis:
- TG broken down to FAs
- FAs oxidised to acetyl CoA and metabolised for energy.
- Extra fatty acids exported to the peripheral tissues.
- Glycerol recycled back to the liver for gluconeogenesis
Muscle metabolism in the early fasting state
- GLUT
- Fatty acids
- Proteins
GLUT 4 dissociates from membrane due to drop in insulin.
- Less glucose metabolism for ATP.
- Glucose stored as glycogen still
No glycogenolysis due to lack of glucagon receptors.
Fatty acids are oxidised for energy.
- Inhibits glycolysis.
Proteolysis release a.a to use for energy or to export to the liver (alanine).
Brain metabolism in the early fasting state
GLUT 1 and 3 still take in glucose due to high affinity.
- Glucose still metabolised for energy.
Fatty acids cannot be used for energy as they cannot cross the blood-brain barrier.
Overall metabolism in late fasting state
Characterised by chronically low insulin and high glucagon
- 3 days or more
- 0.05 insulin:glucagon
Causes decrease in thyroid hormones to decrease metabolic rate.
Fatty acids become the major source of energy.
Liver metabolism in the late fasting state
- GLUT
- Urea
- Fatty acids
- Ketone bodies.
Glycogen stores deplete within 24 hours and no glucose enters the liver. via GLUT2.
Gluconeogenesis:
- Lactate
- Glycerol
- Alanine
- Kidneys also play an equally important role in gluconeogenesis
Increase in urea due to increase in amino acids from proteolysis.
Glycogenesis and glycolysis are inhibited.
Fatty acids:
- Utilised for energy
- Acetyl CoA in excess= ketone bodies.
Ketone bodies:
- Transported to be utilised around the body
- Liver cannot metabolise ketone bodies.
Adipose tissue metabolism in the late fasting state
- GLUT
- Fat
- Glycerol
Very low insulin causes very little glucose entry via GLUT4.
Lipolysis, highly activated by very low insulin:
- TG broken down for energy and to release sources for gluconeogenesis.
- FAs increase in blood by x10-fold.
Glycerol, from lipolysis:
Transported to liver for gluconeogenesis.
Muscle metabolism in the late fasting state
Very low insulin causes very little glucose entry via GLUT4.
Fatty acids used as fuel for energy.
Ketone bodies used as fuel.
- Reduces proteolysis
Proteolysis stimulated by noradrenaline and cortisol—–> gluconeogenesis
Glucose-fatty acid cycle
This is triggered in response glucagon and adrenaline.
Fatty acid oxidation is increased in peripheral tissue to Acetyl CoA.
Excess acetyl CoA is converted to citrate and inhibits PFK-1 (inhibits F6P to FBP).
PFK-1 inhibition builds up G6P—–> inhibits hexokinase.
Hexokinase inhibition causes build up of glucose, preventing entry of glucose.
Brain metabolism in the late fasting state.
Ketone bodies can cross blood-brain barrier.
- Brain utilises for energy
Brain still takes up glucose for glycolysis as it cannot solely metabolise ketone bodies.
Glucagon control on glycogenolysis and gluconeogenesis
- Initiator
- Effect
Initiator—> hypoglycaemia
Effect—> rapidly activates glycogenolysis and gluconeogenesis
Adrenaline control on glycogenolysis and gluconeogenesis
- Initiator
- Effect
Initiator—> hypoglycaemia, stress
Effect—> rapidly activates glycogenolysis and gluconeogenesis
Cortisol control on glycogenolysis and gluconeogenesis
- Initiator
- Effect
Initiator—> stress
Effect—> chronically activates glycogenolysis and gluconeogenesis
Insulin control on glycogenolysis and gluconeogenesis
- Initiator
- Effect
Initiator—> hyperglycaemia
Effect—> inactivates glycogenolysis and gluconeogenesis
Glucagon and adrenaline effect on glycogen phosphorylase/ synthase
They bind to plasma membrane receptors and cause an increase in cAMP.
cAMP activates proteins kinases.
Glucagon works in the liver not muscle.
Adrenaline works on the muscle—> alpha adrenoreceptors
Protein kinase activates phosphorylase kinase by phosphorylation.
- Deactivates synthase= inhibits glycogenesis
Phosphorylase kinase phosphorylates glycogen synthase= inactivation.
- also phosphorylates glycogen phosphorylase.= glycogenolysis
Ca2+ and regulation of phosphorylase
Muscle contraction increases intracellular Ca2+.
Ca2+ allosterically activates phosphorylase kinase——> activates glycogen phosphorylase.
Causes glycogen breakdown.
Insulin effect on glycogen phosphorylase/ synthase
Insulin activates protein phosphatase-1.
- Activates glycogen synthase.
- Deactivates glycogen phosphorylase
Switches of glycogenolysis and stimulates glycogenesis.
Adrenaline control of metabolism difference in muscle and liver.
Beta-receptor—> Muscle
Alpha receptors —-> Liver.
Alpha receptors use phospholipase C (PLC) to activate PKC and Ca2+ dependent kinases
- Deactivates glycogen synthase.
- This is present in the liver as the cAMP pathway will be affected by both insulin and glucagon.
Beta receptors use the cAMP pathway.
