intergration of whole body metabolism Flashcards
Brain
• Uses 100-120g of glucose daily and is its preferred substance
○ Half the energy is used for Na-K transports to maintain membrane potential and synthesis of neurotransmitter ○ Lacks energy stores so glucose is transported by GLUT3 which has a low Km, meaning the transporter is active at most times
○ Dangerous when glucose levels drop below 2.2mM.
○ Fatty acids not usually used for energy but for membrane biosynthesis
Cardiac muscle
• Little or no glycogen stores • Fatty acid main source of energy followed by lactate and ketone bodies.
Adipose tissue
- Store for fatty acids
* Acts as a reservoir of metabolic energy in the form of triglycerides If person starved, FA synthesised by chylomicrons
Kidney
- Produces urine and plasma is filtered up to 60 times a day • Only small volume of urine produced because water soluble material is largely reabsorbed to prevent loss
- During starvation, kidney may contribute half of the blood glucose through gluconeogenesis
Liver
- Regulates metabolism: carbs, fatty acids and amino acids
- Most compounds absorbed by gut pass through liver
- Provides fuel for brain muscle and other peripheral organs
- Takes energy from α-ketoacids-glucose absorbed by hepatocytes used for production of fat synthesis more than the production of energy
Control of blood glucose by liver metabolism
• Glucose transported into hepatocytes by GLUT2 and immediately phosphorylated by glucokinase
○ GLUT-2 is not insulin sensitive
○ GLUT2 is driven by concentration gradient and is a means of regulating low blood glucose levels
• G6P from glycogen breakdown converted to glucose by the action of G6P and transported out the cell into the blood by GLUT-2
Muscle glucose metabolism
- Glucose uptake by GLUT-4 is insulin dependant
- Glucose converted to 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
Fuel for a sprint or a marathon
• ATP directly powers myosin
○ Chemical energy –> movement
○ Muscle ATP stores are small Power and speed dependant on the rate of ATP production
Fuel for sprint
○ Sources of energy: § ATP stores § Glycolysis § Glycogen stores § Creatine phosphate □ Small store of ATP ○ Only provides 5-6 seconds of energy reserves Anaerobic respiration gives lactate and a fall in pH
Fuel for marathon
○ 150 moles of ATP needed ○ Body glycogen will provide only 103 moles
○ Aerobic respiration more efficient
○ Co-operation between muscle, liver and adipose tissue required
§ Because ATP required exceeds that stored by muscles
○ Fats are a large source of ATP, metabolism even slower than glycogen and x10 slower than creatine phosphate
○ More efficient to use both fat and glycogen
§ Regulated by synthesis of acetyl CoA from fat which regulates glucose into TCA At end of marathon, 1/2 glycogen left
Interaction between liver and muscle
- During exercise, glycolysis exceeds the capacity of TCA, pyruvate converted to lactate and transported to liver cori cycle
- Muscle protein also broken down into amino acids-majority is converted to alanine and transported to liver. Used for gluconeogenesis
Fed state
- Amino acids used for protein synthesis or made into keto acids when in excess
- Fats also delivered to muscle via the aid of VLDLs
- Resting muscle use FA as source of energy
- Excess glucose stored as FA in adipocytes or as glycogen in muscle
Post absorptive phase
- Blood glucose falls, insulin level falls and glucagon levels rise
- Phosphorylase a activity increases as does glycogen breakdown
- Drop in insulin reduces glucose uptake by muscle and adipose tissue
Early starvation (4-24 hours)
- Glucose released from 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
Intermediate starvation (1-20 days)
- Glycogen stores almost completely depleted
- Increased lipolysis and ketogenesis
- Increased gluconeogenesis to maintain blood glucose
- 60hrs FA account for 3/4 energy provision
- After 8 days, beta-hydroxybutyrate is raised 50 fold Further starvation sees kidney take over gluconeogenesis from liver