Intergration Of Metabolism

Question 1

What % of body weight is made up of muscle?

Answer 1

40

Question 2

What % of body weight does the brain and nervous tissues make up?

Answer 2

2

Question 3

What % of body weight does adipose tissue make up?

Answer 3

15

Question 4

What % of body weight does the heart make up?

Answer 4

1

Question 5

What % of body weight does the liver make up?

Answer 5

2.5

Question 6

50% of resting metabolic rate is made up by 3 organs. What are those 3 organs and what %s do they make up individually?

Answer 6

Brain - 20
Liver - 20
Heart - 10

Question 7

Why can’t the brain utilise fatty acids as fuel source?

Answer 7

Fatty acids are bound to a protein called albumin in the bloodstream which is unable to pass through the blood brain barrier.

Question 8

How is ATP provided during light muscle contraction?

Answer 8

Oxidative phosphorylation using both glucose and fatty acids as fuels.

Question 9

How is ATP provided during vigorous contraction?

Answer 9

During vigorous contraction, ATP consumption is faster than the ATP supply from oxidative phosphorylation where the diffusion of oxygen, fatty acids and glucose limits rate of ATP production. Therefore, glycogen already present in the muscles are subsequently broken down to produce ATP. Under anaerobic conditions, pyruvate is converted to lactate using lactate dehydrogenase which leaves the muscle and moves through the blood to the liver.

Question 10

Since fatty acids themselves cannot pass through the blood brain barrier, outline how they are indirectly used as fuels for the brain.

Answer 10

Fatty acids are first converted to ketone bodies in the liver which can then be used in the brain alongside glucose.

Question 11

Under what conditions does the heart anaerobically respire?

Answer 11

Only during ischaemia - the heart is not designed for anaerobic respiration.

Question 12

At what plasma glucose concentration would a patient be at risk of a hypoglycaemic coma?

Answer 12

Below 3mM

Question 13

Outline 3 ways the body can avoid hypoglycaemia in the short term

Answer 13

1. Break down liver glycogen stores occur to maintain plasma glucose levels.
2. Release free fatty acids from adipose tissue.
3. Convert acetyl CoA into ketone bodies in the liver.

Question 14

Typically how long does it take for glycogen stores to be exhausted during periods of fasting.

Answer 14

12-18 hours

Question 15

Gluconeogenesis is similar to a reverse reaction to glycolysis since most enzymes involved in glycolysis work both ways. What are the 3 enzymes involved in glycolysis that will not work in gluconeogenesis?

Answer 15

1. Hexokinase
2. Pyruvate kinase
3. PFK

Question 16

Outline the 9 steps of gluconeogenesis

Answer 16

1. Pyruvate formed from lactate using lactate dehydrogenase.
2. The pyruvate is translocated into the mitochondria by MPC (mitochondrial pyruvate carrier). This is because the enzyme pyruvate carboxylase is only present within the mitochondria.
3. The pyruvate is converted to oxaloacetate by pyruvate carboxylase using ATP. Acetyl CoA is an important cofactor and in times of high acetyl CoA concentration this enzyme will be activated converting more pyruvate into oxaloacetate.
4. Oxaloacetate is converted into malate by MDH oxidising NADH to NAD. This reaction is favourable in the mitochondria since the concentration of NADH is higher than NAD. This reaction occurs because oxaloacetate cannot leave the mitochondria whereas malate can leave by the malate-aspartate shuttle. Once the malate enters the cytosol, it is then reconverted back into oxaloacetate using MDH and this reaction becomes favourable since the concentration of NAD is higher than NADH in the cytosol.
5. Once the oxaloacetate is present in the cytosol it can be converted into phosphoenolpyruvate using PEP carboxykinase. This releases a molecule of CO2 and requires GTP for its function.
6. Backwards along the glycolysis pathway until fructose-1,6-bisphosphate.
7. Fructose-1,6-bisphosphate converted to fructose-6-phosphate using fructose bisphosphatase.
8. Fructose-6-phosphate to glucose-6-phosphate.
9. Glucose-6-phosphate to glucose using glucose-6-phosphatase.

Remember 2 pyruvates are required to form glucose.

Question 17

What are the 3 main precursors to gluconeogenesis?

Answer 17

1. Pyruvate - formed from lactate using lactate dehydrogenase
2. Amino acids - can directly form pyruvate or can enter the TCA cycle to form oxaloacetate.
3. Glycerol - First phosphorylated to glycerol phosphate using glycerol kinase and ATP. The glycerol phosphate is then converted to dihydroxyacetone phosphate by glycerol phosphate dehydrogenase which can be converted to glyceraldehyde-3-phosphate using TPI. Forms NADH.

Question 18

How do isoenzymes help to control metabolic pathways such as glycolysis and gluconeogenesis?

Answer 18

Muscle and liver contain different forms of some enzymes such as hexokinase enzymes. Different forms are active at different concentrations of glucose. Hexokinase 1 operates at low levels of glucose and can be inhibited by glucose-6-phosphate which is accumulates in anaerobic conditions. Hexokinase 4 operates at higher levels of glucose and is not inhibited by glucose-6-phosphate.

Question 19

What are the main 4 hormones involved in blood glucose regulation?

Answer 19

Insulin – secreted when glucose levels rise: it stimulates the uptake and use of glucose and storage as glycogen and fat.

Glucagon - secreted when glucose levels fall: it stimulates production of glucose by gluconeogenesis and breakdown of glycogen and fat.

Adrenalin - strong and fast metabolic effects to mobilise glucose for “flight or fight”.

Glucocorticoids - steroid hormones which increase synthesis of metabolic enzymes concerned with glucose availability.

Question 20

What happens after a meal to control the glucose intake?

Answer 20

After a meal, glucose levels rise which is accompanied by an increase in insulin secretion. This causes:

1. increased glucose uptake by liver – used for glycogen synthesis and glycolysis
2. increased glucose uptake and glycogen synthesis in muscle.
3. increased triglyceride synthesis in adipose tissue.
4. increased usage of metabolic intermediates throughout the body due to a general stimulatory effect on synthesis and growth.

Therefore, overall stimulation of anabolic pathways.

Question 21

After some time blood glucose levels begin to fall, how is this controlled?

Answer 21

1. increased glucagon secretion (and reduced insulin) from islets.
2. glucose production in liver resulting from glycogen breakdown and gluconeogenesis.
3. utilisation of fatty acid breakdown as alternative substrate for ATP production (important for preserving glucose for brain).

Question 22

What happens once glycogen stores are exhausted?

Answer 22

1. glucagon/insulin ratio increases further
2. adipose tissue begins to hydrolyse triglyceride to provide fatty acids for metabolism
3. TCA cycle intermediates are reduced in amount to provide substrate for gluconeogenesis
4. protein breakdown provides amino acid substrates for gluconeogenesis
5. ketone bodies are produced from fatty acids and amino acids in liver to substitute partially the brain’s requirement for glucose