Integration of Whole Body Metabolism Flashcards
Each organ has a unique metabolic profile.
Describe the metabolic profile of the brain.
The brain uses 100-120g of glucose daily.
Over half of the energy consumed is used for Na+-K+ transport to maintain membrane potential and the synthesis of neurotransmitters.
It lacks energy stores.
Glucose is transported to the brain by the GLUT3 transporter, which has a low Km, so it is saturated under most conditions.
There’s a danger point when plasma glucose drops to below 2.2 mM.
Normally fatty acids are used for membrane biosynthesis rather than for energy.
Each organ has a unique metabolic profile.
Describe the metabolic profile of the cardiac muscle.
It’s exclusively aerobic, with little or no glycogen stores.
Fatty acids are the main source of energy, followed by lactate and ketone bodies.
Each organ has a unique metabolic profile.
Describe the metabolic profile of the adipose tissue.
They reservoir metabolic energy in the form of triglycerides (a 70kg man would have 15kg of triglycerides on average).
Although the liver does make fatty acids, we get most of them from our diet. These are delivered by chylomicrons.
Each organ has a unique metabolic profile.
Describe the metabolic profile of the kidney.
Its major role is to produce urine.
The plasma is filtered almost 60 times daily, yet only a small amount of urine is produced. This is because water-soluble material is largely reabsorbed to prevent loss.
Although they only make up about 0.5% of the body’s mass, they consume about 10% of the body’s energy.
During starvation, the kidney may contribute up to half of the blood glucose through gluconeogenesis.
Each organ has a unique metabolic profile.
Describe the metabolic profile of the liver.
It plays a central role in regulating metabolism (with carbohydrates, fatty acids, amino acids, etc.).
It takes its energy from α-keto acids.
Most products absorbed by the gut passes through the liver.
It provides fuel for the brain, muscles and other peripheral organs.
How do we control blood glucose by liver metabolism?
Glucose is transported into hepatocytes by GLUT2 (not insulin-sensitive) and is immediately phosphorylated by glucokinase.
G6P 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 GLUT2.
Describe muscle glucose metabolism.
Muscle has a different glucose transporter, the GLUT4. It is converted into G6P once inside by hexokinase (it has a low Km), allowing low glucose concentration in the cell.
Muscle doesn’t have glucose-6-phosphatase so cannot convert G6P back to glucose. Instead, the G6P will be used for the synthesis of glycogen or immediate use in glycolysis. So muscle uses energy through oxidation of glucose but also stores it, but only for its own use. Glucose is mobilised from glycogen in exercise.
Describe how the muscles provide energy to run a sprint.
ATP directly powers myosin; it converts chemical energy to movement.
However, muscle ATP stores are small, as well as this all chemical reactions take time so for a 9-second burst this is very short when we need that ATP instantly.
A 100m sprint is powered by:
- ATP stores -> used quickly
- Glycolysis -> anaerobic
- Glycogen -> for short time
- Creatine phosphate
The muscle contains creatine phosphate which can react with ADP to give ATP and creatine.
Sprinting is an anaerobic activity. Anaerobic breakdown of glycogen stores gives lactate and a fall in pH
Describe how the muscles provide energy to run a marathon.
Marathon running requires co-operation between the muscle, liver and adipose tissue. This is because the amount of ATP required needs to be generated over a longer period of time and exceeds that stored by the muscle. However, because we have more time, we can use a more efficient way of getting that ATP, ie. aerobic respiration.
For a marathon, we need 150 moles of ATP, but the body glycogen will only provide 103 moles of ATP (but by the end, we will still have about half our glycogen store left as body switches to fat metabolism).
Fats are a large source of ATP, the metabolism is slower than glycogen and 10x slower than creatine phosphate. A sprinter uses glucose, while a marathon runner uses fatty acids to generate Acetyl CoA to generate triglycerides. Some protein may also be broken down (as we need to maintain blood glucose so the brain has enough).
Even in a marathon, there will be some generation of lactate.
Where do we get our alanine and lactate from?
We get our alanine through protein degradation and lactate through anaerobic respiration. These can be transported in the circulation to the liver where they are fed into the gluconeogenic pathway.
This glucose can be used as an energy source for muscle or put into circulation to maintain circulating levels for the activity of the brain.
Describe the fed state and we would expect to see in it (with regards to pathways and molecules).
In the fed state, blood glucose will be maintained and brain will take what is needed. If there is an excess of calorific intake (through carb), then that excess will be converted to fatty acids and stored in adipocytes. It may also be transported to muscle where a little can be stored as fat or glucose as glycogen.
We will see: IN REGARDS TO PATHWAYS - Glycolysis increases - Glycogen synthesis increases - Glycogenolysis decreases (we don’t want to produce glucose when we have sufficient levels in blood) - Gluconeogenesis decreases (we don’t want to produce glucose when we have sufficient levels in blood) - Fatty acid synthesis increases - Fatty acid degradation decreases
IN REGARDS TO MOLECULES
- Glycogen increases
- Glucose decreases
- Fatty acids increase
- Ketone bodies decrease
What happens when we stop eating (in terms of energy)?
When you stop eating, there is an almost immediate drop in consumption of energy (in a healthy individual by 40%) if you restrict your diet by a third. But there is still an energy requirement that has to be met.
This is done by means of the post-absorptive phase.
Describe what happens in the post-absorptive state and what we will see (with regards to pathways and molecules)
The post-absorptive phase occurs several hours after the last meal or if you restrict your diet. The main energy source to re-stablish glucose levels is glycogen. Hence there will be an increase in Phosphorylase A activity to increase glycogen breakdown.
We will see: IN REGARDS TO PATHWAYS - Glycolysis decreases - Glycogen synthesis decreases - Glycogenolysis increases - Gluconeogenesis increases - Fatty acid synthesis decreases - Fatty acid degradation increases
IN REGARDS TO MOLECULES
- Glycogen decreases
- Glucose increases
- Fatty acids decrease
- Ketone bodies increase
Describe what happens during early starvation (4-24 hours).
Glucose is released from the liver due to gluconeogenesis and glycogenolysis then transferred to the brain for oxidative phosphorylation.
Other tissues are moving towards using fatty acids and ketone bodies for their energy, so there is mobilisation of fatty acids from adipose tissue. Glucose use falls as muscle switches to fatty acid oxidation. Insulin drops, causing GLUT4 expression my muscles to fall, reducing glucose uptake.
After around 12 hours, 45% of resting energy is derived from fatty acids and 40% from glucose, since most glucose is needed to maintain brain activity.
Describe what happens during intermediate starvation (1-20 days).
Glycogen stores get depleted, so there is increased lipolysis and ketogenesis. There’s also increased gluconeogenesis to maintain blood glucose.
Further starvation sees the kidney take over gluconeogenesis from the liver So in moving from fed to starved state, we move from carb source of energy to fatty acid, then for prolonged we will start breaking down structural proteins.
