intergration of whole body metabolism

Question 1

Brain

Answer 1

• 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

Question 2

Cardiac muscle

Answer 2

• Little or no glycogen stores • Fatty acid main source of energy followed by lactate and ketone bodies.

Question 3

Adipose tissue

Answer 3

• Store for fatty acids

* Acts as a reservoir of metabolic energy in the form of triglycerides If person starved, FA synthesised by chylomicrons

Question 4

Kidney

Answer 4

• 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

Question 5

Liver

Answer 5

• 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

Question 6

Control of blood glucose by liver metabolism

Answer 6

• 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

Question 7

Muscle glucose metabolism

Answer 7

• 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

Question 8

Fuel for a sprint or a marathon

Answer 8

• ATP directly powers myosin
○ Chemical energy –> movement
○ Muscle ATP stores are small Power and speed dependant on the rate of ATP production

Question 9

Fuel for sprint

Answer 9

○ 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

Question 10

Fuel for marathon

Answer 10

○ 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

Question 11

Interaction between liver and muscle

Answer 11

• 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

Question 12

Fed state

Answer 12

• 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

Question 13

Post absorptive phase

Answer 13

• 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

Question 14

Early starvation (4-24 hours)

Answer 14

• 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

Question 15

Intermediate starvation (1-20 days)

Answer 15

• 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

Question 16

Prolonged starvation (>3 wks)

Answer 16

• Β 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 recycled by cori cycle
• Glycerol and amino acids are oxidized Proteins are broken down muscle forming amino acid precursors

Question 17

Skeletal muscle

Answer 17

• Alanine also formed by transamination of pyruvate and released into blood where it is taken up by liver and converted to glucose Because muscle can use amino acids for carbon skeleton but cannot form urea therefore the liver removes nitrogen and release pyruvate