Integration of Whole Body Metabolism Flashcards
(17 cards)
Describe the fuel source needed for sprinting and the interaction between the liver and muscle during a sprint
Rapid mobilisation of energy stores:
- ATP directly powers muscle contraction
- Power and speed dependent on availability of ATP
- Muscle ATP stores small
Largely anaerobic:
- ATP stores
- Glycolysis
- Glycogenolysis
100m sprint powered by:
- Creatine phosphate
- Creatine phosphate + ADP → ATP + Creatine (via Creatine kinase)
- Build up of lactate and fall in pH ultimately limits performance
Liver and muscle:
- The liver is able to synthesise G6P from:
- Alanine or lactate which can be converted into pyruvate, which is then converted into G6P
- Glycogen which can be broken down into G6P
- G6P can then be converted into glucose, and this can then be transferred to the muscle
- The muscle breaks glucose down via glycolysis into pyruvate. Pyruvate can enter the anaerobic pathway and produce lactate, which can be converted pyruvate and transferred to the liver, where the above happens
- Pyruvate can be converted into alanine, or alanine can form as a result of protein degradation, this can then be transferred to the liver where the above occurs
Describe the fuel source needed for a marathon and the interaction between the liver and muscle during a marathon
- Requires sustained energy provision
- Uses aerobic = More efficient
- Needs co-operation of muscle, liver and adipose tissue
- Initially glycogen used, but later fat mobilised from adipose tissue
- Fats are large sources of ATP, but metabolism is 10x slower than creatine phosphate
- Combined use of both glycogen and fats is most efficient
- Result is approximately half of glycogen stores remain
Describe the role of the liver in maintenance of blood glucose
- Glucose is transported into hepatocytes by GLUT-2 (not insulin dependent) and is immediately phosphorylated by glucokinase, forming G6P, which can then be used to synthesise glycogen
- G6P from 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
Describe glucose metabolism by muscle
- Glucose uptake by GLUT-4 is insulin dependent
- Glucose is converted into G6P by hexokinase
- Low free glucose in cell
- Glucose is movilised from glycogen in exercise
- Glycolysis of the G6P is a rapid source of ATP
What is the difference between hexokinase and glucokinase?
Glucokinase:
- Glucokinase is found primarily in the liver and pancreatic beta cells, and has a lower affinity for glucose than hexokinase
- Glucokinase is induced by insulin and regulated by glucokinase regulatory protein (GKRP), which localises it in the hepatocyte nucleus
- In the pancreas, it’s glucose sensing, and in the liver, it converts glucose into glycogen
Hexokinase:
- Hexokinase is found in most tissues, including skeletal muscle and has a higher affinity for glucose than glucokinase
- It phosphorylates glucose in order to produce energy
What is the main source of energy in cardiac muscle?
- Cardiac muscle is exclusively aerobic with little or no glycgoen stores
- FAs are the main source of energy followed by lactate and ketone bodies
- Lactate → pyruvate → acetyl coA
Describe the role of adipose tissue in energy storage
- Reservoir of metabolic energy in form of triglycerides
- 70 kg man will have 15kg TG
- TG come either from the diet and delivered by chylomicrons or synthesised in the liver and transported by VLDL
- Glucose transported across adipose tissue via GLUT-4, which is insulin-dependent
Describe the role of the kidneys in starvation
Although only 0.5% body mass, consumes 10% of the energy
During starvation, the kidney may contribute half of the blood glucose through gluconeogenesis
What does the liver receive its energy from?
α-ketoacids
- Plays central role in regulating metabolism - Carbs, FA, Amino acids
- Most compounds absorbed by gut pass through liver
- Provides fuel for brain, muscle, other peripheral organs
What are the pathways and molecules inhibited or stimulated in the fed state?
Stimulated:
- Glycolysis
- Glycogen synthesis
- Fatty acid synthesis
- Glycogen
- Fatty acids
Inhibited:
- Glycogenolysis
- Gluconeogenesis
- Fatty acid degradation
- Glucose
- Ketone bodies
What are the main priorities when we stop eating?
- 1st priority is to maintain glucose lvls
- 2nd priority is to preserve protein
Too achieve this, metabolism shifts from glucose to FAs and ketone bodies
Describe the events in the post absorptive phase
Several hrs after last meal
- Blood glucose falls, insulin levels fall, glucagon lvls rise
- Phsophorylase A activity increases, as does glycogen breakdown
- Drop in insulin reduces glucose uptake by muscle and adipose tissue
Describe 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 gluose uptake
- After 12hrs, 45% resting energy from FA, 40% from glucose
- Initial increase in protein breakdown
Describe the events that occur throughout 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 kidney take over gluconeogenesis from the liver
Describe the events that occur throughout prolonged starvation (> 3 weeks)
- B-hydroxybutyrate plateaux at 20 days
- As brain starts to move to using ketone bodies the need for glucose fall 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
- Protein are broken down by the muscle forming amino acid precursors
What is over half the energy consumed by the brain used for?
Na+/K+ transport to maintain membrane potential and the synthesis of NTs BUT the brain lacks energy stores
How is glucose transported in the brain?
Via GLUT 3, has low Km (affinity) - Saturated under most conditions
