4 - Liver Function and Nutritional States in the Starve:Feed Cycle Flashcards
How are nutrients delivered to the liver and what is the exception?
Absorbed in small intestine into the blood stream and enters liver via hepatic portal vein, except dietary fats
What are some of the metabolic functions the liver carries out?
- Storage of glycogen; regulation of homeostasis; conversion of fructose and galactose
- Synthesis and oxidation of fatty acids and formation of ketone bodies (liver does not store significant triglyerides)
- Oxidation of amino acids with the formation of urea
- Modification of steroids, hormones and xenobiotics
- Production and recycling of bile salts
- Maintains energy supply to body tissues under various healthy nutritional and disease states
The majority of the livers energy demand is met by the oxidation of glucose.
True or false? + explain
False
Amino acids
Excess carbohydrate is converted to fat during ‘well fed’ conditions.
True or false? + explain
True
Majority of glucose entering the liver immediately after a meal is not stored but is distributed to other tissues.
True or false? + explain
True
GLUT2 = low affinity
During fasting conditions the brain is able to oxidise fatty acids to derive energy.
True or false? + explain
False
Technically speaking it can but transport is limited, so generally false
Mainly ketone bodies
Oxidation of FFA during fasting conditions provides substrates for gluconeogenesis.
True or false? + explain
False
Excess amino acids provide substrates for fatty acid synthesis during ‘well-fed’ conditions.
True or false? + explain
True
Amino acids provide substrates for gluconeogensis during fasting conditions.
True or false? + explain
True
Majority of amino acids can, main one being alanine
What does the brain require for energy?
Glucose and oxygen
What is the purpose of adipose tissue?
a long term energy store; brown fat has an important thermogenic role
What do the kidneys require for energy?
actively consume oxygen
filter about 800 litres of blood a day to provide 200 litres of filtrate which reduces to ~ 2 litres of urine
How does Metabolic specialisation arise in organs/tissues?
Differential gene expression
Each system has its particular set of enzymes and transporters
Why is inter-organ/tissue cooperation of metabolic processes essential?
- Maximise nutrient storage during ‘well fed’ conditions
- Maintain energy supply during ‘starved’ or ‘fasting states’
- Respond quickly to changes in nutrient supply/demand
- Response to prolonged or severe changes
Describe and draw the Cori Cycle
glucose recycling
no net gain of glucose
in starvation
Interrupted in well-fed state
Describe and draw the Glucose:Alanine Cycle
prolonged fasting
from protein degradation
Describe and draw the Glucose:Fatty Acid Cycle
Fatty acid oxidation can “spare” glucose oxidation (glycolysis)
Describe what happens during the Well-Fed state, draw out what happens to each nutrient in each organ
Glucose and amino acids enter the blood stream and reach the liver via the portal vein
Dietary triacylglycerol is packed into chylomicrons
Insulin is secreted to stimulate the storage of fuels
Glycogen synthesis occurs in liver and muscles
Glycolysis occurs in the liver which generates acetyl-
CoA for fatty acid synthesis
FFAs produced by the liver are converted to TAG and packaged into VLDL particles
Insulin promotes FFA hydrolysis and uptake into adipose by activating lipoprotein lipase in adipose
Glucose uptake into muscle from GLUT4 translocation
What happens to glucose going from well-fed to fasting?
the graph slide 12
Describe what happens during the Early Fasting state (post absorption), draw out what happens to each nutrient in each organ
Blood glucose levels drop and glucagon is secreted
Glycogenolysis is stimulated to release glucose
Glucose is taken up primarily by the brain
Gluconeogenesis is stimulated
Main source of gluconeogenic precursors provided from the glucose:alanine cycle and Cori cycle
Recall: Cori cycle ‘recycles’ glucose via lactate (no net output)
Describe what happens during the Fasting state, draw out what happens to each nutrient in each organ
Liver will deliver ~130mg/min glucose
~80mg from glycogen (initially)
Glucose is no longer taken up by the muscles
Low insulin levels reduces activity of LPL whilst hormone sensitive lipase (HSL) becomes active
Hydrolysis of stored TAG
FFAs used for energy or ketogenesis
Glycerol for gluconeogensis
The brain begins to rely more upon ketone bodies
Muscles use fatty acids and ketone bodies (glucose:fatty acid cycle ‘spares’ glucose for the brain)
Proteins are broken down, leading to atrophy
Amino acids (particularly alanine and glutamine), lactate and glycerol are all used to maintain a supply of glucose for the brain
Long-term starvation leads to brain malfunction
What are the three main substrates for gluconeogenesis?
Alanine, lactate, glycerol
How does the insulin:glucagon ratio affect hormones and metabolic fuels in the blood?
Slide 17 graph drop insulin and raise in glucagon --> rise in breakdown of fatty acids --> drop in glucose ONLY at lowest levels of insulin -> rise in ketone bodies (ketogenesis) drop in glycogen
Describe what happens during the Early Refed state (absorption)
Insulin is secreted in response to rising [glucose]
Liver maintains gluconeogenesis and diverts glucose to other organs and peripheral tissues
Glucose from gluconeogenesis is used to build up glycogen stores before dietary glucose is available
Excess glucose is converted into fat for storage
Metabolic pathways in the liver of a well-fed person?
Glycolysis
glycogenesis
lipogenesis
Metabolic pathways in the liver of a fasting person?
Gluconeogenesis, ketogenesis lipolysis glycogenolysis proteolysis
Name 5 mechanisms which Homeostasis is regulated by the liver
Tissue-specific and cellular-specific (compartmentation) expression
Induction of enzymes (gene expression; prolonged changes)
Covalent modification
Allosteric effectors
Substrate availability
Briefly outline the principle metabolic functions of the liver during well fed and fasting conditions
Think
Discuss the role of the liver in coordinated metabolic processes in the starve:feed cycle
Think
Discuss the importance of the Cori cycle and glucose:alanine cycles during mild fasting conditions
Think
Describe how the insulin:glucagon ratio is responsible for controlling the uptake and liberation of FFAs from adipose during well fed and starved conditions
Think
“High fat, low carb diets are better for weight loss” do you agree with this statement? In terms of the active processes in and between tissues, discuss the possible metabolic consequences of such a diet and any effects in terms of weight loss
Think
