The Feed Fast Cycle. Flashcards
Define enzyme induction?
An increase of the amount of a particular enzyme in a certain tissue.
What is the well fed state also known as?
The absorptive state.
The post prandial phase.
How long does the absorptive state last for?
Around 2-4 hours after a meal has been consumed.
What nutrients are in high concentrations in the well fed state?
Proteins.
Glucose.
Fatty acids.
What hormone is released in the well fed state?
Insulin.
Is the well fed state an anabolic or catabolic state?
An anabolic state.
Why is the well fed state considered to be anabolic state?
As the nutrients consumed are used to build various structures such as glucagon and TAGS.
What nutrient is the main provider of fuel that is used to build molecules in the body?
Glucose.
What organs will have an altered metabolism in the well fed state?
The liver.
The muscle.
Adipose tissue.
The brain.
How many mechanisms are there that control the rate of metabolism within the body by influencing enzyme activity?
4.
What are the 4 mechanisms that control the rate of metabolism within the body by influencing enzyme activity and what are there speeds?
Availability of an enzymes substrate. (Fast).
Allosteric activation and inhibition of enzymes. (Fast).
Covalent modification of enzymes e.g. phosphorylation and de-phosphorylation by phosphatase’s. (Fast or slow).
Induction and repression of enzyme synthesis. (Slow).
In the well fed state, what will alter how enzymes function?
Insulin.
Can the 4 4 mechanisms that control the rate of metabolism within the body by influencing enzyme activity occur at the same time?
Yes.
How are most of the enzymes modified in the well fed state?
Most are covalently modified and activated by de-phosphorylation.
Will insulin phosphorylate or de-phosphorylate enzymes?
De-phosphorylate.
What enzymes will insulin de-phosphorylate to inhibit them?
Glycogen phosphorylase.
Fructose bisphosphatase 2.
Hormone sensitive lipase.
The dephosphorylation of hormone sensitive lipase inhibits what process?
TAG degradation.
Will fructose 2,6 bisphosphate produced in the well fed state?
Yes.
Fructose 2,6 bisphosphate stimulates what metabolic process?
Glycolysis.
Is fructose 2,6 bisphosphate produced in the glycolysis pathway?
No.
It is produced in a separate pathway.
What glycolytic enzyme will the presence of fructose 2,6 bisphosphate stimulate?
Phosphofructokinase-1 (PFK-1).
What gluconeogenic enzyme will the presence of fructose 2,6 bisphosphate inhibit?
Fructose 1,6-bisphosphatase.
What enzymes make up the bi-functional enzyme in step 3 of glycolysis?
Phosphofructokinase-1.
Fructose bisphosphatase-2.
Is the bi-functional enzyme in step 3 of glycolysis phosphorylated in the well fed state or the fasting state?
In the fasting state.
Is the bi-functional enzyme in step 3 of glycolysis de-phosphorylated in the well fed state or the fasting state?
In the well fed state.
What process occurs if the bi-functional enzyme in step 3 of glycolysis or gluconeogenesis is de-phosphorylated?
Glycolysis.
What process occurs if the bi-functional enzyme in step 3 of glycolysis or gluconeogenesis is phosphorylated?
Gluconeogenesis.
If the bi-functional enzyme in step 3 of glycolysis or gluconeogenesis is phosphorylated, what enzyme will be active?
Phospho-fructokinase-2.
If the bi-functional enzyme in step 3 of glycolysis or gluconeogenesis is de-phosphorylated, what enzyme will be active?
Fructose bisphosphatase-2.
What is the job of phospho-fructokinase-2 in glycolysis?
It converts fructose 6 phosphate to fructose 2,6-BP.
What is the job of fructose bisphosphatase-2 in glycolysis?
It converts fructose 2,-BP to fructose 6 phosphate.
Is glycogen synthase phosphorylated in the well fed state or in the fasting state?
In the well fed state.
Will insulin de-phosphorylate glycogen synthase?
Yes.
What glycogenic enzyme is inhibited by insulin?
Glycogen phosphorylase.
What is glycogen synthase A?
Active glycogen synthase that is de-phosphorylated.
What is glycogen synthase B?
Inactive glycogen synthase that is phosphorylated.
What is glycogen phosphorylase A?
Active glycogen phosphorylase that is phosphorylated.
What is glycogen phosphorylase B?
Inactive glycogen phosphorylase that is de-phosphorylated.
When insulin de-phosphorylates glycogen phosphorylase, what process in inhibited?
Glycogen degradation.
What is the job of pyruvate kinase?
It is the final enzyme of glycolysis and forms pyruvate.
What type of process will inhibit pyruvate kinase?
Covalent modification.
How does insulin activate pyruvate kinase?
It de-phosphorylates it.
How does glucagon inhibit pyruvate kinase?
It phosphorylates it.
Will pyruvate kinase be inhibited in the well fed or fasting state?
It is active in the well fed state.
It is inactive in the fasting state.
Is the pyruvate de-hydrogenase complex active when it is phosphorylated or de-phosphorylated?
When it is de-phosphorylated.
What will inhibit the pyruvate de-hydrogenase complex?
Phosphorylation by glucagon.
What process is ACoA carboxylase the key enzyme for?
Fatty acid synthesis.
What is the substrate for ACoA carboxylase?
ACoA.
When is ACoA carboxylase inactivated?
When it is phosphorylated by glucagon.
When is ACoA carboxylase activated?
When it is de-phosphorylated by insulin.
What enzymes will be inhibited by de-phosphorylation by insulin?
Glycogen phosphorylase.
Fructose bisphosphatase 2.
Hormone sensitive lipase.
What molecules is the liver flooded with after a meal has been consumed?
Glucose.
Amino acids.
Chylomicron remnants.
What does the liver use glucose for?
To make glycogen.
What does the liver use amino acids for?
For protein synthesis.
What does the liver use chylomicron remnants for?
To make TAGs.
Which glucose transporter brings glucose into the liver from the bloodstream?
GLUT-2 transporters.
Are GLUT-2 transporters insulin sensitive?
No.
What will activate GLUT-2 transporters to bring glucose into the liver from the bloodstream?
High blood glucose levels.
What percentage of all glucose in the bloodstream is used up by the liver?
Around 60%.
Consumption of a lot of carbohydrates means that the liver will make a lot of what molecules?
Glycogen.
Pyruvate.
What can pyruvate be converted to in the PDH complex?
ACoA.
What can ACoA be used for?
Fatty acid synthesis.
It can enter the TCA cycle.
What is a glycolytic intermediate that can make glycerol phosphate?
Dihydroxyacetone phosphate (DHAP).
What can glycerol phosphate be used to make?
The glycerol backbone found in TAGs.
What will the liver use amino acids for?
Protein synthesis.
To make ACoA.
To make intermediates for the TCA cycle.
Can the liver can be thought of as a centre for the processing and distribution of nutrients?
Yes.
How many available nutrients will the liver use up?
It will use all the nutrients that it needs.
What does the liver do with all the nutrients that it doesn’t need?
They will will be released as VLDL lipids.
Any excess glucose will be stored as glycogen.
What tissue is used to store excess fatty acids?
Adipose tissue.
Adipose tissue stores fatty acids in what form?
As TAGs.
How does adipose tissue pick up fatty acids?
From circulating chylomicrons and VLDL molecules.
What happens to TAGs when energy levels are low.
They are degraded into free fatty acids and glycerol and the fatty acids are used for energy production.
What transporters will bring glucose into adipose tissue from the bloodstream?
GLUT-4 transporters.
What provides energy for adipose tissue?
Glycolysis.
What glycolytic intermediate can adipose tissue use to make the glycerol backbone used in TAGs?
DHAP.
In the well fed state is there an increase in glucose uptake by adipose tissue
Yes.
What enzyme is de-activated by insulin?
Hormone sensitive lipase (HSL).
Is glucose uptake in skeletal muscle is increased in the well fed state?
Yes.
What glucose transporters bring glucose from the blood into the muscle?
GLUT-4.
What is the glucose that is bought into the muscle cells used for?
To replenish muscular glycogen stores and to provide energy via glycolysis etc.
What are the amino acids that enter the muscle tissue used for?
To replace proteins that have been broken down by exercise or fasting.
What are the 2 anabolic processes that the muscle is involved in in the well fed state?
Protein and glycogen synthesis.
How much glucose will the brain take from the bloodstream?
All of the glucose that it needs.
What kind of glucose transporters bring glucose from the blood into the brain?
High affinity glucose transporters such as GLUT-1 and GLUT-3.
What happens to glucose once it enters the brain?
It is oxidised to form CO2, water and energy.
Which glucose transporters are insulin sensitive?
GLUT-4 transporters.
Which tissues are said to be insulin sensitive?
Muscle and adipose tissue.
Are the brain or red blood cells insulin sensitive?
No.
As they are always picking up glucose.
Does insulin induce the liver to take up glucose from the bloodstream?
No.
Glucose enters the liver because glucose levels are high.
What tissues are amino acids usually supplied to?
Most tissues, particularly the liver and muscle for protein synthesis.
How are chylomicron remnants usually supplied to the body?
Via dietary fats.
What happens to chylomicron remnants in the liver?
The fatty acids are picked up by lipoprotein-lipase (LPL) and stored in the adipocytes.
What is the fasting state also known as?
The post absorptive phase.
When does the fasting state usually begin?
Around 4-5 hours after a meal has been consumed.
What decreases in the blood during the fasting state?
A decrease in blood glucose, amino acids and lipoproteins.
How will the fasting state affect hormone levels?
There will be a decrease insulin synthesis and an increase in glucagon and epinephrine.
What effects does the fasting state have on the liver?
The liver will synthesise glucose.
Why does the liver synthesise glucose in the fasting state?
As red blood cells and the brain need glucose to be able to continue functioning.
Is the fasting state a catabolic or anabolic hormone?
Catabolic.
What is the function of the liver in the fasting state?
It start to produce glucose instead of consuming it.
What kind of factory does the liver become in the fasting state?
A glucose factory.
What are the 2 methods that the liver uses to produce glucose?
Glycogenolysis via the break down of glycogen.
The synthesis of of glucose via gluconeogenesis.
What provides the energy for the liver in the fasting state?
The β oxidation of fatty acids.
When the liver starts to oxidises fatty acids, what metabolic process will also be increased?
Ketogenesis.
What enzyme will glucagon and epinephrine activate in fat tissue and what does this enzyme do?
Hormone sensitive lipase which will break down TAGS to release fatty acids and glycerol into the bloodstream.
What can the glycerol that is released from beta oxidation of fatty acids be used for in the fasting state?
Glycerol can become a precursor of gluconeogenesis via conversion to glycerol phosphate and then to DHAP.
How are the cleaved free fatty acids transported through the bloodstream in the fasting state.?
They are bound to albumin.
Where are the free fatty acids that are cleaved by HSL delivered to?
Multiple tissues.
Is the muscle fuelled by glucose in the fasting state?
No. (except by its own glycogen stores).
What processes will provide the energy for the muscle tissue in the fasting state?
The β oxidation of fatty acids.
Ketone bodies.
How does the muscle contribute to gluconeogenesis?
It will degrade proteins to provide amino acids for gluconeogenesis.
What will power the brain in the fasting state?
Glucose that is produced by the liver via gluconeogenesis.
If fasting continues for a very long time will the brain still run on glucose?
No.
If fasting goes on long enough then the brain will be powered by glucose and ketone bodies.
What prompts the brain to be powered by ketone bodies?
When the concentration of ketone bodies in the blood is high.
How long does it take for the brain to start running on ketone bodies?
Around 2 weeks.
What is the smallest of the bodies energy reserves?
Glycogen stores.
What is the second largest of the bodies energy stores?
Protein which is around 24 times larger than glycogen stores.
What is the largest of the bodies energy stores?
Fat store which has around 5 times more energy than protein storage and around 140 times more than glycogen.
What are the average weights of the bodies 3 energy stores?
Glycogen = 0.2 Kg.
Proteins = 6 Kg.
Fats = 15 Kg.
What storage is incredibly important during fasts?
Fat storage, as it has so much energy.
What is glycogen degraded to give?
Glucose.
When will proteins be used as an energy source?
When they are turned over.
How do proteins give energy?
They are degraded to amino acids which can be converted to ketone acids which can be used to make glucose.
What form of energy are fats degraded to give?
ACoA which can be oxidised TCA cycle.
What pathways are activated by glucagon and epinephrine?
Gluconeogenesis.
Glycogen degradation.
Beta oxidation of fatty acids.
The production of glucagon will up-regulate and activate enzymes in what processes?
Glucose and energy making processes.
What 3 enzymes are up-regulated in the fasting state?
PEP carboxykinase.
Fructose 1,6 bisphosphatase.
Glucose 6-phosphatase.
What 2 gluconeogenic enzymes are activated in the fasting state?
Pyruvate carboxylase.
Fructose 1,6-bisphosphatase.
How is pyruvate carboxylase activated in the fasting state?
By ACoA from fatty acid oxidation.
By phosphorylation.
How is fructose 1,6 bisphosphatase activated in the fasting state?
By decreased fructose 2,6 bisphosphate due to phosphorylation of PFK-1.
What glycolytic enzyme becomes less active in the fasting state?
Glucokinase as it works at high glucose concentrations.
What organs will use amino acids from the breakdown of muscle proteins to make glucose?
The liver and sometimes the kidneys.
What is common pathway that converts amino acids to pyruvate?
The glucose-alanine pathway.
How many alanines need to be converted to how many pyruvates to make a glucose molecule?
2 alanines will converted to 2 pyruvate molecules which are converted to 1 glucose molecule.
What pathway converts pyruvate to glucose?
Gluconeogenesis.
Can ACoA be used for gluconeogenesis?
Yes.
Where is ACoA derived from in the fasting state?
From the β oxidation of fatty acids.
Glucagon will cause an up-regulation of which gluconeogenic enzymes in the fasting state?
Glucose-6-phosphatase.
Fructose-1-6-bisphosphatase.
PEP carboxykinase.
What is the first metabolic pathway to be activated in the fasting state?
Glycogenolysis in the liver.
What pathways takes over from glycogenolysis in the fasting state?
As glycogen stores decrease, gluconeogenesis will take over and will synthesise glucose.
How long will gluconeogenesis carry on producing glucose for after a meal?
For a long time after a meal and will continue for very long periods of time.
Is muscle glycogen broken down in short fasts?
No.
Only in long fasts.
What are the 3 main precursors for gluconeogenesis?
Amino acids from muscle.
Lactate.
Glycerol.
What gluconeogenic pathway is obtained via the CORI cycle?
Lactate.
When is lactate released into the bloodstream?
In anaerobic glycolysis by cells that lack mitochondria.
By exercising muscle.
What happens to lactate in the fasting state?
It enters the bloodstream and is picked up by the liver to enter the CORI cycle.
What happens in the CORI cycle?
Lactate is converted to pyruvate.
Pyruvate can then enter gluconeogenesis.
What enzyme converts lactate to pyruvate in the CORI cycle?
Lactate dehydrogenase.
What pathway commonly converts amino acids to pyruvate?
The alanine pyruvate cycle.
What happens in the alanine pyruvate cycle?
Alanine from protein turnover is released into the blood where it will travel to the liver.
In the liver alanine is converted to pyruvate.
Is alanine the only amino acid that can be converted to pyruvate?
No.
Many other amino acids can be converted to pyruvate but, alanine is the most common.
What initiates the liver to start using fatty acids as an energy source?
Glucagon which is active when blood glucose levels are low.
What happens to the levels of fatty acids in the blood after a few hours of fasting?
After a few hours of fasting, the amount of fatty acids in the blood will rise quite sharply before levelling off.
What is the main source of fatty acids in the beta oxidation of fatty acids?
TAGs from adipose tissue.
What stimulates the breakdown of TAGs?
It is due lipolysis which is the due to the stimulation of HSL by epinephrine via the beta adrenergic receptor.
Fatty acids in the blood can provide energy to what organs in the fasting state?
The liver.
Muscle tissue.
Other tissues.
The beta oxidation of fatty acids provides what molecule?
ACoA.
The liver use ACoA to make what molecule in the fasting state?
Ketone bodies.
Why does the liver make ketone bodies?
ACoA can’t be released in the bloodstream, so ketone bodies transport ACoA to cells that use them for metabolism.
What form are the 2 forms that ketone bodies released in?
Beta hydroxybuterate.
Acetoacetate.
How long does it take for ketone bodies to be released by the liver?
After a short amount of time in starvation.
How will the concentration of ketone bodies rise as a fast continues?
They will to rise to a higher level than fatty acids.
How long does a period of starvation need to take before the body will mostly run on ketone bodies?
After 2 weeks of starvation.
Can the brain pick up ketone bodies at low concentrations?
No.
When will the brain pick up ketone bodies?
After long periods of starvation when a high concentration of ketone bodies will be present in the blood
After a long period of fasting, what will the brain use to gain energy?
50% glucose and 50% ketone bodies for its energy.
Ketone bodies are an alternative to what energy source?
Ketone bodies.
What are ketone bodies derived from?
2 ACoAs.
What is the most common ketone body?
3-hydroxybuterate.
What is the only organ that can make ketone bodies?
The liver.
What tissue can use ketone bodies?
Tissues that have mitochondria.
What energy source will adipose tissue provide the body with in the fasting state?
Fatty acids.
What molecule stores most acids in adipose tissue?
TAGs.
Are more or less chylomicrons found in the blood during the fasting state?
Fewer as the fatty acids are being broken down rather than stored.
Does muscle tissue pick up glucose from the blood in the fasting state?
No.
What powers muscle tissue in the fasting state?
Fatty acids and ketone bodies.
What energy source is provided by the muscle in the fasting state?
Large amounts of amino acids from protein degradation that can be used for glucose synthesis by the liver.
