Energy in fed/fasting state (F1 8/12)

Question 1

LO’s

Answer 1

1. Describe the sources of energy available during the fed and fasting state
2. Describe the role of glycogen and ketone bodies
3. Describe the role of insulin, glucagon and other counter-regulatory hormones in the control of metabolism

Question 2

Select the blood glucose that would be considered hypoglyceamic:

1. 2 mmol/l
2. 4.5 mmol/l
3. 5.1 mmol/l
4. 5.7 mmol/l
5. 7.8 mmol/l

Answer 2

Hypoglycemia occurs when blood glucose levels fall below 4 mmol/L. So 2 mmol/l is correct. Hyperglyceamia if blood glucose over 7mmol/l.

Question 3

Which of the following enzymes is not directly involved in glycolysis:

1. Glucokinase
2. Hexokinase
3. Phosphofructokinase
4. Pyruvate dehydrogenase
5. Pyruvaste kinase

Answer 3

• Pyruvate dehydrogenase is not involved in glycolysis.
• Glucokinase converts glucose to glucose-6-phosphate in the liver.
• Hexokinase converts glucose to glucose-6-phosphate in all the other tissues apart from the liver.
• Phosphofructokinase converts fructose-6-phosphate to fructose-1,6-bisphosphate.
• Pyruvate kinase converts phosphoenolpyruvate to pyruvate.

Question 4

One molecule of this process is oxidised by this process to make 3xNADH and 1xFADH2

Answer 4

Krebs/TCA Cycle

Question 5

In which order do you use up your energy sources?

Answer 5

1. Glucose
2. Glycogen
3. Gluconeogenesis

Question 6

Which glucose transporter is stimulated by insulin?

Answer 6

GLUT4

Question 7

Which of the following enzymes is stimulated by glycogen?

1. Glycogen Synthase
2. Glycogen Phosphorylase
3. Glucokinase
4. Phosphoglucomutase
5. UDP-glucose Pyrophosphorlase

Answer 7

Glycogen phosphorylase breaks down glycogen.

Question 8

What is insulin secretion promoted and inhibited by?

Answer 8

• Insulin secretion from the B-cells of the islets of langerhans is promoted by high blood glucose.
• Insulin secretion is inhibited by epinephrine.

Question 9

What is glucagon secretion promoted and inhibited by?

Answer 9

• Glugagon release from the alpha-cells of the Islets of Langerhans is promoted by low blood glucose and by epinephrine.
• Glucagon release is ihibited by insulin release.

Question 10

What happens to insulin and glucagon when you have low blood glucose?

Answer 10

• Insulin levels go down.
• Glucagon levels go up.

Question 11

What happens to insulin and glucagon when you have high blood glucose?

Answer 11

• Insulin levels go up.
• Glucagon levels go down.

Question 12

Why are insulin and glucagon counter-regulatory hormones- with an example?

Answer 12

The effect of one cancels out the effect of the other. Insulin promotes the production of glycogen, but glucagon promotes the breakdown of glycogen.

Question 13

What drives the secrtetion or non-secretion of glucagon and insulin?

Answer 13

Blood glucose levels.

Question 14

What is glycogenesis and glycogenolysis?

Answer 14

• Making glycogen from glucose in the liver and skeletal muscle is glycogenesis.
• Glycogenolysis: is breaking down glycogen in the liver and skeletal muscle.

Question 15

What is gluconeogenesis?

Answer 15

When the body doesn’t have enough glucose from carbohydrates in the diet, so it has to make glucose itself from non-carbohydrate sources, like lactate, glycerol and glucogenic amino acids.

Question 16

What is protein production and when does it happen?

Answer 16

• Protein production is the replenishment of cellular proteins.
• It happens when insulin levels are high.
• Protein breakdown happens when glucagon levels are high.

Question 17

How does cellular glucose uptake happen after a meal?

Answer 17

• Insulin activates GLUT4 in liver and adipocytes.

Question 18

What is ketogenesis?

Answer 18

• The breakdown of TAG in the adipocytes to fatty acids and glycerol.
• The fatty acids go to the liver and are converted into ketones, which the brain can use as an alternative energy source.

Question 19

What does TAG production refer to?

Answer 19

Making TAG when there is excess glucose, from fatty acids and glycerol.

Question 20

What is lipolysis?

Answer 20

• TAG breakdown to fatty acids and glycerol.

Question 21

In the fed state, how does insulin drive metabolic pathways?

Answer 21

• Cellular glucose uptake is increased
• Protein production is increased
• TAG profuction is increased
• Glycogenesis (making glucagon) is increased.
• But in liver, glycolysis (making glucose) is increased: to convert glucose into other storage substances.

Question 22

In the fasting state, how does glucagon drive metabolic pathways?

Answer 22

• Glycogenolysis is promoted
• Protein breakdown happens
• Ketogenosis happens
• Lipolysis/TAG breakdown happens
• Gluconeogenesis (making glucose) is promoted
• In liver, glycolysis (breaking down glucose) is decreased in the fasting state.

Question 23

What are the typical energy stores in a 70kg male?

Answer 23

• 0.1kg of liver glycogen (skeletal glycogen is used in excercise, not released into bloodstream): lasts 10/18 hours after a meal. This is used to maintain blood glucose homeostatsis during the initial peroid of the fast.
• 15kg of fat: enough energy to last 3 months.
• 6kg of protein in skeletal muscle.

Question 24

How is fat stored and used in the body during a fast?

Answer 24

• Fat is stored as triacylglycerides in adipose tissue around belly, thighs and back of kidneys.
• During fast TAGs are broken down.
• Glycerol can be converted to glucose using gluconeogenosis.
• Fatty acids can be oxidised to ketone bodies in liver.

Question 25

How is protein stored and used in the body during a fast?

Answer 25

• Rapid breakdown into amino acids during initial fasting period.
• Slow breakdown after initial fasting period.
• In starvation loss of protein leads to malfunction of vital organs.
• Amino acids can be catabolised for energy.
• Glucogenic amino acids can be converted to glucose.

Question 26

What are alternative sources of blood glucose and when are they used?

Answer 26

• First glucose from carbohydrates is used for energy. This is the exogenous source.
• Then glycogen from the liver is used forur to 20 hours after a meal.
• Then gluconeogenesis in the liver happens. It uses components from TAG and protein breakdown.

Question 27

What alternate fuels are there for the brain?

Answer 27

• In the well fed state the brain uses glucose.
• In the fasting state only a small percentage of glucose (made from gluconeogenesis) is used for energy. Mainly, the brain gets energy from ketones when it is starving ( 3-hydroxy-butyrate and acetoacetate). The brain gets a small percentage of energy from amino acids from the breakdown of skeletal muscle and body tissue.

Question 28

Describe Ketones

Answer 28

• They are an alternative fuel to glucose in the fasting state .
• Made by the liver mitochondria by converting fatty acids into acetyl coA using fatty acid oxidation and then ketone bodies.
• It can be used by brain, skeletal and cardiac muscle.
• Liver can not use ketone bodies, only produces them, otherwise it would soak all the ketone bodies up and use them itself.
• Ketone bodies enter the krebs cycle in all tissue except the liver (extrahepatic) and produce ATP.
• Ketone bodies reduce reliance on glucose during fast.
• There are three main ketone bodies:

1. 3-hydroxybutyrate (major)
2. acetoacetate
3. acetone (not used, breathed off)

Question 29

Describe glycogen metabolism and the enzymes involved

Answer 29

• High blood glucose
• High insulin levels
• Glyconeogenesis happens
• Glucose is first converted to glucose-6-phosphate.
• Glucose 6 phosphate is converted into glucose 1 phosphate using the enzyme phosphoglucomutase.
• Glucose 1 phosphate is then converted into UDP-glucose using the UDP-glucose Pyrophosphorylase enzyme.
• Lastly, UDP-glucose is converted into glycogen by glycogen synthase.
• When there are high glycogen levels: glycogen is converted into glucose 1 phosphate using glycogen phosphorylase.

Question 30

Describe the glycogen synthase enzyme

Answer 30

• Converts UDP-Glucose into glycogen.
• Glycogen synthase becomes activated when it is dephosphorylated.
• Dephosphorylation of glycogen synthase is promoted by insulin.

Question 31

Describe glycogen phosphorylase enzyme

Answer 31

• In the fasting state, when glucagon levels are high, glucolysis happens.
• Glycogen is converted into glucose 1 phosphate by glycogen phosphorylase.
• Glycogen phosphorylase is only active when it phosphorylated by glucagon.

Question 32

Describe gluconeogenesis:

• what is it
• when is it used
• what are the three substrates
• where does it occur
• why does it require energy and where does it get it from

Answer 32

• Gluconeogenesis is the formation of glucose from non-carbohydrate precursors.
• This is the third thing that maintains blood glucose in a fasting state after exogenous/dietary glucose and glycogen is used up.
• The substrates for gluconeogenesis:
  
  • Alpha-ketoacids (the protein skeletan without the amine group). Gluconeogenic amino acids can be converted to oxaloacetate, which can then be converted to 2-phosphenol pyruvate using PEP carboxykinase.
  • Glycerol: from the hydrolysis of TAG in adipose tissue.Taken up by liver and converted into DHAP.
  • Lactate: we get this from anaerobic glycolysis during excercise. The lactate is converted to pyruvate by the liver in the cori cycle. The pruvate is then converted into oxaloacetate using pyruvate carboxylase.
• Occurs mainly in the liver, in the cytosol and mitochondria.
• Gluconeogenesis requires some energy from fatty acid oxidation, because it is an anobolic process (making something).

Question 33

Why is gluconeogenesis not the reversal of glycolysis?

Answer 33

• Gluconeogenesis is making glucose from non-carbohydrate precursors.
• Since there are 3 irreversible steps in glycolysis you can’t go backwards (btw the fructose 1,6 bisphosphate to DHAP is not irreversible even though there is a single arrow because it can form a cycle using glyceraldehyde).
• Gluconeogenesis has to use a different pathway.

Question 34

What are the key enzymes in gluconeogenesis?

Answer 34

• Normally in glycolysis, the hexokinase enzyme (or glucokinase in the liver) converts glucose to glucose 6 phosphate irreversibly. In gluconeogenesis this is bypassed by glucose 6 phosphatase.
• Also, normally fructose 6 phosphate is converted into fructose 1,6 bisphosphate by phosphofructokinase. In gluconeogenesis this is bypassed by fructose 1,6 bisphosphatase.
• Also, pyruvate kinase normally converts 2-phosphoenolpyruvate into pyruvate. In gluconeogenesis this is bypassed by PEP carboxykinase, which converts oxaloacetate into 2-phosphoenolpyruvate.

The substrates for gluconeogenesis:

• Alpha-ketoacids (the protein skeleton without the amine group). Gluconeogenic amino acids can be converted to oxaloacetate, which can then be converted to 2-phosphenol pyruvate using PEP carboxykinase.
• Glycerol: from the hydrolysis of TAG in adipose tissue. Taken up by liver and converted into DHAP. Then converted into glyceraldehyde 3 phosphate and back up the cycle.
• Lactate: we get this from anaerobic glycolysis during excercise. The lactate is converted to pyruvate by the liver in the cori cycle. The pruvate is then converted into oxaloacetate using pyruvate carboxylase.