Integration of Whole Body Metabolism Flashcards
Different organs and tissues have different needs but can use the …?
…the same molecules but in different ways. These needs and they way they use particular metabolites may change with circumstances such as disease. These changes may affect how one organ interacts with another organ.
What is the metabolic profile of the brain?
- The brain uses about 100-120g of glucose daily with glucose as its preferred substance. Over half the energy is used for Na-K transports to maintain membrane potential and the synthesis of neurotransmitter.
- It lacks energy stores and so glucose is transported by GLUT3 transport which has a low Km i.e. saturated at low conditions. This means the transporter is maximally active at most times.
- Danger point is when glucose levels drop below 2.2 mM. Fatty acids are usually not used for energy but for membrane biosynthesis.
What is the metabolic profile cardiac muscle?
-This is exclusively aerobic with little or no glycogen stores.
-Fatty acids are the main source of energy followed by lactate and ketone bodies. Lactate is converted as shown below:
lactate –> pyruvate –> acetyl CoA
What is the metabolic profile of adipose tissue?
-Adipose tissue is the store for fatty acids – it acts as a reservoir of metabolic energy in the form of triglycerides –70kg man will have 15kg of
triglycerides.
-Although the liver makes FA we get most from our diet. However if a person is starved of nutrients and is in the recovery period they will synthesise more FAs. These are delivered by the chylomicrons.
What is the metabolic profile of kidneys?
- Has major role is to produce urine and the plasma is filtered up to 60 times a day.
- Only a small volume of urine is produced as water soluble material is largely reabsorbed to prevent loss.
- Although it is only 0.5% of body mass it consumes about 10% of the energy
- During starvation the kidney may contribute half of the blood glucose through gluconeogenesis
What is the metabolic profile of the liver?
-Plays a central role in regulating metabolism: carbs, fatty acids (receives this through lymphs)and amino acids.
-Most compounds absorbed by gut pass through the liver.
-It provides fuel for the brain, muscle and other peripheral organs.
-It takes energy from α-ketoacids – very little of the glucose that is absorbed by hepatocytes is used for production of energy - it uses its glucose for other things such as fat synthesis.
Look at notes for graph.
How is blood glucose controlled by liver metabolism?
-The liver also has different set of transporters. It has predominantly GLUT2 transporter – the expression of GLUT2 is not insulin sensitive so it’s not regulated by concentration of insulin
-The liver also has glucose 6 phosphatase which converts glucose 6 phosphate back to glucose.
-This transporter is driven by concentration gradient – when glucose concentration is high inside the cell the tendency for transporter to move into the blood. Due to this it can function as a means of regulating low blood glucose levels.
-Glucose is transported into hepatocytes 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.
Look at diagram
What occurs in muscle glucose metabolism?
-Muscle has an insulin-dependent glucose transporter GLUT4 and doesn’t possess the enzyme that converts glucose-6-phosphate to glucose. Excess glucose taken up by muscle will be largely converted to glycogen.
* 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
Look at diagram
What is the position of the liver compared to other organs in regards to maintaining blood glucose?
-The liver is very much at the centre- it will act as a source of energy for the brain.
-It also interacts with adipocytes – donating and receiving fatty acids from adipocytes. The same is also true for muscle.
-Kidney is an end user.
-One of the sources of nutrients is the gut.
And there are two stores.
Look at diagram
Examples to illustrate this:
* Metabolic difference between running 100m and running a marathon
* Fed and unfed state
* Lifestyle
What are the factors involved for a marathon or sprint, metabolically?
-ATP directly powers myosin
* Converts chemical energy to movement
* Muscle ATP stores are small
-Power and speed is dependent on rate of ATP
production
What are the energy sources for muscles during a 100m sprint?
-ATP stores
-Glycolysis – can occur under anaerobic but it’s not very efficient
-Glycogen stores – timely
-Creatine phosphate – quickly mobilised
*Muscle creatine phosphate small store of ATP
*Only provides 5-6 seconds of energy reserves. So to
run 100m we need ATP, glycolysis and creatine
phosphate. However lactate is also produced which
the body cannot handle due to its acidic nature.
What are the energy sources for muscles during a marathon?
- There is time for metabolism to work. It requires cooperation between muscle, liver and adipose tissue and mobilisation of fatty acids.
- Why? Because the amount of ATP required exceeds that stored by the muscle.
- Aerobic respiration is used as it is more efficient
- For a marathon need about 150 moles ATP. The body glycogen will provide only 103 mole ATP.
- Fats are a large source of ATP, the metabolism is even slower than glycogen and x10 slower than creatine phosphate.
- More efficient to use both fat and glycogen - this is regulated by the synthesis of acetyl CoA from fat which regulates glucose into TCA.
- At end of a marathon about ½ glycogen is left.
What is the interaction between the liver and muscle?
- During exercise glycolysis exceeds the capacity of the citric acid cycle, pyruvate is converted to lactate and transported to liver
- This is called the Cori cycle: Look a notes for diagram.
- The muscle protein is also broken down into amino acids – majority is converted to alanine and this is transported to liver. This used for gluconeogenesis.
What is the fed state?
-There is a constant supply of energy to the brain and kidneys.
-In the fed state the flow of molecules will be initially to the liver. From the liver it will either store the glucose in adipocytes and muscles.
-In the liver the glucose will also be used to generated NADPH in pentose phosphate pathway – one of the substrates for FA synthesis
-The amino acids are used for proteins synthesis or made into keto acids when in excess.
-Fats will also delivered to muscle via the aid of VLDLs
-Resting muscle will uses FA as a source of energy
-Any excess glucose is stored as FA in adipocytes or as glycogen in the muscle
Look at notes for the diagram.
What is the unfed state?
-When we stop eating
-Energy consumption dropped by 40% in healthy volunteers on a diet restricted by 1/3. But where do they get the remaining requirement?
-Post absorptive phase: Several hours after the last meal blood glucose decrease and the major energy source is glycogen. There is an increase in phosphorylase a activity which helps mobilise glycogen.
-Towards the end of the postabsorptive period the glucose concentration in the portal blood will fall leading to an increase in the active form of the enzyme phosphorylase a in the liver.
Look at notes for the diagram.
