Integration + Metabolism Flashcards
How much glucose does the brain use daily?
100-120g glucose daily
What’s the energy used for by the brain?
for Na+-K+ transport to maintain membrane potential + synthesis of neurotransmitters
Role of GLUT3?
glucose transport in brain
has a low Km – saturated under most conditions
What’s the danger point of brain?
when plasma glucose drops to below 2.2mM
How does brain use FA?
not for energy but for membrane biosynthesis
How much CO does brain use?
Brain is approx. 2% of body mass but takes 20% of the cardiac output
Main source of energy for cardiac muscle?
- FA
- lactate
- ketone bodies
What does adipose tissue contain?
Reservoir metabolic energy in form of TAG
How much TAG does 70kg man have?
15kg of TAG
How’s FA delivered?
by chylomicrons
Role of GLUT4?
Glucose is transported to adipose tissue
Glucose uptake is insulin sensitive
Glucose transported to striated muscle
Role of kidney?
- Produce urine
- Plasma filtered up 60 times daily
- Water soluble material reabsorbed to prevent loss
- During starvation contributes half of blood glucose via gluconeogenesis
How much energy does kidney consume?
only 0.5% body mass but consumes 10% of the energy
Role of liver?
- Plays central role in regulating metabolism: carb, FA, AA
- Provides fuel for brain, muscle, other peripheral organs
Where does liver get energy?
takes its energy from α-ketoacids
Role of GLUT2?
Transports glucose into hepatocytes (not insulin-sensitive)
Transports glucose out of the cell into blood
Role of glucokinase?
phosphorylates glucose
Role of glucose-6 phosphatase?
converts G6P from glycogen breakdown (or gluconeogenesis) to glucose
Describe muscle glucose metabolism
- 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
Role of hexokinase?
glucose -> G6P
Fuel for a sprint or marathon?
- ATP directly powers myosin
- Converts chemical energy to movement
- Muscle ATP stores are small
- Power + speed dependent on rate of ATP production
What does resting muscle use as a major source of energy?
FA
What’s a sprint powered by?
ATP stores
Glycolysis
Glycogen
Creatine phosphate
What’s muscle creatine phosphate?
small store of ATP
Creatine phosphate + ADP ATP + creatine
Role of creatine?
via
Creatine phosphate + ADP ATP + creatine
Role of kinase?
via
creatine + ATP creatine phosphate + ADP
What causes a fall in pH?
Anaerobic breakdown of glycogen stores gives lactate
How’s activity of glycogen phosphorylase enhanced?
by phosphorylation
What’s a marathon powered by?
- 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
Interaction between liver + muscle?
During exercise glycolysis exceeds capacity of citric acid cycle, pyruvate -> lactate + transported to liver Cori cycle so lactate -> glucose
Pathways during fed state?
Glycolysis ↑. Glycogen synthesis ↑. Glycogenolysis ↓ (don’t want to produce glucose when sufficient levels in blood). Gluconeogenesis ↓ (““). FA synthesis ↑. FA degradation ↓.
Molecules during fed state?
- Glycogen ↑.
- Glucose ↓.
- FA ↑.
- Ketone bodies ↓
What happens when you stop eating?
- 1st priority to maintain glucose levels
- 2nd priority to preserve protein
- metabolism shifts from glucose -> FA -> ketone bodies
Describe what happens during post absoptive phase
- 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
Describe what happens during early starvation 24hrs
- 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
Describe what happens during immediate starvation 3-20 days
- 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
Describe what happens during prolonged starvation 3wks
- 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
How’s alanine formed?
by transamination of pyruvate
How skeletal muscle provides energy source from AA?
-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
Summary of starvation?
- 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
