Integration of metabolism

Question 1

What fuels the brain?

Answer 1

Continuous supply of glucose

Cannot use fatty acids

Can use ketone bodies as a partial substitute

Question 2

What can hypo/hyperglycaemia do to the brain?

Answer 2

Hypo: faintness and coma
Hyper: irreversible damage

Question 3

What fuels skeletal muscle at rest and during contraction?

Answer 3

Light contractions requirements met my OP

Vigorous contractions - O2 becomes a limiting factor : glycogen breakdown occurs in muscles and lactate formation occurs

Question 4

What fuels the heart?

Answer 4

Designed for complete aerobic metabolism = rich in mitochondria

Uses TCA substrates: free fatty acids, ketone, lactate, glucose

Question 5

What can happen if there is a loss of O2 supply to the heart?

Answer 5

Myocardiac infarction

Question 6

What are the roles of the liver?

Answer 6

Highly metabolically active

Central role in maintaining blood glucose

Glucose storage organ

Lipoprotein metabolism

Question 7

What can excess glucose 6 phosphate do?

Answer 7

Generate glycogen in the liver and muscle

Question 8

What can excess Acetyl CoA be used for?

Answer 8

Generate fatty acids : stored as triglycerides in adipose

Question 9

Why is lactate produced?

Answer 9

During extreme exercise the ATP demands of muscle outstrip the oxygen needed for aerobic respiration

= lactate made

Question 10

What changes occur during fasting?

Answer 10

Instead of Acetyl CoA entering TCA, it is used to ketone body production

Question 11

What is the pentose phosphate pathway?

Answer 11

Glucose 6 phosphate can be used as a source of nucleotides which also produced the bulk of NADPH needed

Question 12

What does the body do, short term, to avoid hypoglycaemia?

Answer 12

breakdown liver glycogen = glucose

Release fatty acids from adipose

convert acetyl CoA = ketone bodies

• muscle can use the fatty acid and ketone bodies leaving more glucose for the brain
• once glycogen is depleted gluconeogenesis kicks in

Question 13

What is gluconeogenesis?

Answer 13

Making glucose from pyruvate

Pyruvate -->
Oxaloacetate --> 
Phosphoenol pyruvate -->
G3P ( + DHAP ) -->
Fructose 1,6 biphosphate -->
Fructose 6 phosphate -->
Glucose 6 phosphate -->
Glucose

Question 14

What is the cori cycle and how is it relevant to gluconeogenesis?

Answer 14

The Cori cycle:

generation of pyruvate from lactate in the liver and lactate dehydrogenase

Question 15

Why is glycerol relevant to gluconeogenesis?

Answer 15

glycerol is used in generating dihydrocyyacetone phosphate ( DHAP ) which is in glycolysis and needed for gluconeogenesis

Question 16

What are bypass reactions of gluconeogenesis?

Answer 16

Glycolysis has 3 irreversible reactions catalysed by the kinases. So these three reactions have to be bypassed on the way back to glucose

Question 17

Where does the first bypass reaction take place?

Answer 17

Mitochondria ( the rest in cytosol )

pyruvate carboxylase to make oxaloacetate

Question 18

What bypass enzyme is used for pyruvate kinase?

Answer 18

Phosphoenolpyruvate carboxykinase

Question 19

What bypass enzyme is used against phosphofructokinase?

Answer 19

Fructose 1,6 biphosphate

Question 20

What bypass enzyme is used against hexokinase?

Answer 20

Glucose 6 phosphatase

Question 21

What is the difference in gluconeogenesis and glycolysis reversal?

Answer 21

Gluconeogenesis not a reversal at the reactions have to be bypassed with other enzymes. To make it energetically favourable.

G ( glycolysis reverse ) = +90

G ( gluconeogenesis ) = -38

Question 22

What is the difference between glucogenic and ketogenic amino acids?

Answer 22

Glucogenic: amino acids whose skeletons can give rise to glucose via gluconeogenesis

Ketogenic: amino acids give rise to skeletons used for fatty acid and ketone body synthesis

Question 23

What happens to the products of triglyceride breakdown?

Answer 23

Broken down into fatty acids and glycerol

Glycerol –> DHAP in gluconogenic pathway

Fatty acids –> converted to ketone bodies

Question 24

What occurs during aerobic exercise?

Answer 24

• contractions increase ATP demands
• contractions increase glucose transport
• Muscle glycolysis increases ( adrenalin )
• gluconeogenesis increases ( adrenaline )
• fatty acids increase ( adrenaline )

Question 25

As muscle contracts the demand for ATP increases, why?

Answer 25

Actomyosin ATPase requirements increase

Question 26

What occurs during anaerobic exercise?

Answer 26

• ATP demand cannot be matched by O2 delivery
• transport cannot keep up with glucose demand
• muscle glycogen breakdown increases
• lactate increases
• liver uses lactate to form glucose ( recovery )

Question 27

What are the differences in the hexokinase in the muscle and in the liver?

Answer 27

Contain isoforms of this enzyme

Maximally active at different concentrations of glucose.

Km in muscle = 0.1mM =active at low levels of glucose and inhibited by accumulating levels of glucose 6 phosphate

Km in liver = 4mM = less sensitive to blood glucose and the inhibitory effects of glucose 6 phosphate

Question 28

What does glucose 6 phosphatase do?

Answer 28

Found in the liver not muscle

Catalyse reverse reaction to hexokinase, generating glucose from glucose 6 phosphate

Question 29

What do glucocorticoids do for hormonal control of blood glucose levels?

Answer 29

steroid hormone which increase synthesis of metabolic enzymes concerned with glucose availability

Question 30

What happens after a long fast?

Answer 30

• Glucagon/insulin ratio increases further
• Adipose tissue hydrolyses triglycerides to provide fatty acids for metabolism
• TCA cycle intermediates redules to provide substates for gluconeogenesis
• protein breakdown provides amino acid substrates for gluconeogenesis
• ketone bodies are produced from fatty acids and amino acids in liver to substitute partially the brain’s requirement for glucose