Integration + Metabolism

Question 1

How much glucose does the brain use daily?

Answer 1

100-120g glucose daily

Question 2

What’s the energy used for by the brain?

Answer 2

for Na+-K+ transport to maintain membrane potential + synthesis of neurotransmitters

Question 3

Role of GLUT3?

Answer 3

glucose transport in brain

has a low Km – saturated under most conditions

Question 4

What’s the danger point of brain?

Answer 4

when plasma glucose drops to below 2.2mM

Question 5

How does brain use FA?

Answer 5

not for energy but for membrane biosynthesis

Question 6

How much CO does brain use?

Answer 6

Brain is approx. 2% of body mass but takes 20% of the cardiac output

Question 7

Main source of energy for cardiac muscle?

Answer 7

• FA
• lactate
• ketone bodies

Question 8

What does adipose tissue contain?

Answer 8

Reservoir metabolic energy in form of TAG

Question 9

How much TAG does 70kg man have?

Answer 9

15kg of TAG

Question 10

How’s FA delivered?

Answer 10

by chylomicrons

Question 11

Role of GLUT4?

Answer 11

Glucose is transported to adipose tissue
Glucose uptake is insulin sensitive
Glucose transported to striated muscle

Question 12

Role of kidney?

Answer 12

• Produce urine
• Plasma filtered up 60 times daily
• Water soluble material reabsorbed to prevent loss
• During starvation contributes half of blood glucose via gluconeogenesis

Question 13

How much energy does kidney consume?

Answer 13

only 0.5% body mass but consumes 10% of the energy

Question 14

Role of liver?

Answer 14

• Plays central role in regulating metabolism: carb, FA, AA

- Provides fuel for brain, muscle, other peripheral organs

Question 15

Where does liver get energy?

Answer 15

takes its energy from α-ketoacids

Question 16

Role of GLUT2?

Answer 16

Transports glucose into hepatocytes (not insulin-sensitive)

Transports glucose out of the cell into blood

Question 17

Role of glucokinase?

Answer 17

phosphorylates glucose

Question 18

Role of glucose-6 phosphatase?

Answer 18

converts G6P from glycogen breakdown (or gluconeogenesis) to glucose

Question 19

Describe muscle glucose metabolism

Answer 19

• glucose uptake by GLUT4 is insulin-dependent
• glucose -> G6P by hexokinase (Km 0.1mM for glucose)
• low free [glucose] in cell
• glucose mobilised from glycogen in exercise
• glycolysis of G6P is rapid source of ATP

Question 20

Role of hexokinase?

Answer 20

glucose -> G6P

Question 21

Fuel for a sprint or marathon?

Answer 21

• ATP directly powers myosin
• Converts chemical energy to movement
• Muscle ATP stores are small
• Power + speed dependent on rate of ATP production

Question 22

What does resting muscle use as a major source of energy?

Answer 22

FA

Question 23

What’s a sprint powered by?

Answer 23

ATP stores
Glycolysis
Glycogen
Creatine phosphate

Question 24

What’s muscle creatine phosphate?

Answer 24

small store of ATP

Creatine phosphate + ADP ATP + creatine

Question 25

Role of creatine?

Answer 25

via | Creatine phosphate + ADP ATP + creatine

Question 26

Role of kinase?

Answer 26

via | creatine + ATP creatine phosphate + ADP

Question 27

What causes a fall in pH?

Answer 27

Anaerobic breakdown of glycogen stores gives lactate

Question 28

How's activity of glycogen phosphorylase enhanced?

Answer 28

by phosphorylation

Question 29

What's a marathon powered by?

Answer 29

- Need 150 moles ATP - Body glycogen provides only 103 moles - Aerobic respiration more efficient - Co-operation between muscle, liver, adipose tissue because ATP required > stored by muscle - Complete oxidation slow - Fats source of ATP, metabolism slower than glycogen + x10 slower than creatine phosphate - Use FA ->ACoA -> TCA - ½ glycogen is left at end of marathon

Question 30

Interaction between liver + muscle?

Answer 30

During exercise glycolysis exceeds capacity of citric acid cycle, pyruvate -> lactate + transported to liver Cori cycle so lactate -> glucose

Question 31

Pathways during fed state?

Answer 31

``` Glycolysis ↑. Glycogen synthesis ↑. Glycogenolysis ↓ (don’t want to produce glucose when sufficient levels in blood). Gluconeogenesis ↓ (““). FA synthesis ↑. FA degradation ↓. ```

Question 32

Molecules during fed state?

Answer 32

- Glycogen ↑. - Glucose ↓. - FA ↑. - Ketone bodies ↓

Question 33

What happens when you stop eating?

Answer 33

- 1st priority to maintain glucose levels - 2nd priority to preserve protein - metabolism shifts from glucose -> FA -> ketone bodies

Question 34

Describe what happens during post absoptive phase

Answer 34

- glucose falls - insulin levels fall - glucagon levels rise - phosphorylase a activity increases in liver - glycogen breakdown increases - drop in insulin reduces glucose uptake by muscle + adipose tissue

Question 35

Describe what happens during early starvation 24hrs

Answer 35

- glucose released from liver due to gluconeogenesis + glycogenolysis - mobilisation of FA from adipose tissue - glucose use falls as muscle switches to FA oxidation - insulin drops causing GLUT4 expression by muscle to fall reducing glucose uptake - 45% of resting energy from FA + 40% from glucose

Question 36

Describe what happens during immediate starvation 3-20 days

Answer 36

- glycogen stores depleted - increased lipolysis + ketogenesis - increased gluconeogenesis to maintain blood glucose - ¾ energy from FA at 60hrs - β hydroxybutyrate is raised 50 fold at 8 days - kidney take over gluconeogenesis from liver

Question 37

Describe what happens during prolonged starvation 3wks

Answer 37

- β hydroxybutyrate plateaux at 20 days - brain uses ketone bodies - need for glucose falls from 100g to 40g/day - lactate + glycerol used as gluconeogenic precursors - lactate recycled by the Cori cycle - glycerol + AA oxidized - proteins -> AA

Question 38

How's alanine formed?

Answer 38

by transamination of pyruvate

Question 39

How skeletal muscle provides energy source from AA?

Answer 39

-alanine released into blood -taken up by liver -converted to glucose because muscle can use AA for C skeleton but can't form urea so liver removes N + releases pyruvate

Question 40

Summary of starvation?

Answer 40

- protein breakdown in muscle when brain starts to use KB + need for glucose is reduced - 2wks muscle use FA from adipocytes + KB from liver - prolonged starvation gluconeogenesis by kidney amounts to 50% of total - KB in liver releases ACoA allowing beta oxidation