Integration of Whole Body Metabolism Flashcards
Metabolism for the brain?
Uses 100-120g glucose daily
Over half the energy consumed is used for Na+-K+ transport to maintain membrane potential and the synthesis of neurotransmitters
Lacks energy stores
Glucose is transported by GLUT3 which has a low Km- saturated under most conditions
Danger point when plasma glucose drops to below 2.2mM
Normally fatty acids are not used for energy but for membrane biosynthesis
Metabolism for cardiac muscle?
Is exclusively aerobic with little or no glycogen stores
Fatty acids are the main source of energy followed by lactate and ketone bodies
lactate—> pyruvate—> acetyl CoA
Metabolism for adipose tissue?
Reservoir metabolic energy in the form of triglycerides
A 70kg man will have 15kg of TG
TG come either from the diet and delivered by chylomicrons
Synthesised by the liver and transported by VLDL
Glucose is transported by GLUT4
GLUT4 is insulin sensitive
Metabolism for the kidney?
Major role is to produce urine
The plasma is filtered up 60 times daily
Only a small volume of urine is produced
Water soluble material largely reabsorbed to prevent loss
Although only 0.5% body mass they consume 10% of the energy
During starvation the kidney may contribute half of the blood glucose through gluconeogenesis
Metabolism for the liver?
Plays a central role in regulating metabolism
Carbohydrate
Fatty acid
Amino acids
Most components absorbed by gut pass through the liver
Provides fuel for brain, muscle and other peripheral organs
Takes its energy from a-ketoacids
How is blood glucose controlled by liver metabolism?
Glucose is transported into hepatocyte by GLUT-2 (not insulin-sensitive) and immediately phosphorylated by glucokinase
Glucose-6-phosphate from glycogen breakdown (or gluconeogenesis) is converted to glucose by the action of glucose-6-phosphatase and transported out of the cell and into the blood by Glut-2
How does muscle glucose metabolism work?
Glucose uptake by Glut4 is insulin-dependent
Glucose is converted into G6P by hexokinase (Km 0.1mM for glucose)
Low free [glucose] in cell
Glucose is mobilised from glycogen in exercise
Glycolysis of the G6P is a rapid source of ATP
How does our body harness fuel for a sprint?
Rapid mobilisation of energy stores ATP directly powers muscle contraction Power and speed is dependent on the availability of ATP Muscle ARP stores are small Largely anaerobic: ATP stores Glycolysis Glycogenolysis 100m sprint powered by: Creatine phosphate Relatively small but rapidly mobilised ATP store lasting only a few seconds The build up of lactate and the fall in pH ultimately limits performance
How does our body harness fuel for a marathon?
Requires sustained energy provision
Uses aerobic respiration is more efficient
Requires co-operation of the muscle, liver and adipose tissue
Initially glycogen is used but later fat is mobilised from the adipose tissue
Fats are a large source of ATP, but metabolism is x10 slower than creatine phosphate
The combined use of both glycogen and fats is the efficient
The result is approximately half of the glycogen stores remain
What is our body’s priorities when we stop eating?
1st priority to maintain glucose levels
2nd priority to preserve protein
To achieve this metabolism shifts from glucose to fatty acids and ketone bodies
What happens in the post absorptive phase (several hours after the last meal)?
Blood glucose falls, insulin levels fall and glucagon levels rise
Phosphorylase a activity increases as does glycogen breakdown
Drop in insulin reduces glucose uptake by muscle and adipose tissue
What happens during early starvation (24hrs)
Glucose released from the liver due to gluconeogenesis and 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
After 12hrs 45% of resting energy from FA and 40% from glucose
Initial increase in protein breakdown
What happens during intermediate starvation (3-20 days)?
Glycogen stores depleted
Increased lipolysis and ketogenesis
Increased gluconeogenesis to maintain blood glucose
60hrs FA account for 3/4 energy provision
After 8 days b-hydroxybutyrate is raised 50 fold
Further starvation sees the kidney take over gluconeogenesis from the liver
What happens during prolonged starvation (>3wks)
b-hydroxybutyrate plateaux at 20 days
As brain starts to move to using ketone bodies the need for glucose falls from 100g to 40g/day
Other sources of gluconeogenic precursors are lactate and glycerol
Lactate is recycled by the Cori cycle
Glycerol and amino acids are oxidised
Proteins are broken down by the muscle forming amino acid precursors
