BIOC Lecture 9: Starvation and Ketosis Flashcards
What concepts are involved in energy homeostasis?
- Maintain blood glucose
- Making alternative fuels available
- Sparing of glucose and structural body proteins
Why is the liver the ‘king’ of metabolism?
Because it can essentially do everything
What 2 tissues can make new glucose?
The liver and kidney
What can the liver and kidney do (processes)?
- Use, store and make new glucose
- Supply other tissues with glucose
- Synthesise and store Fatty acids
- Form ketone bodies
Compared to the liver - brain, adipose and kidney are much more?
Specific
What is adipose specialised for?
Using and storing fat - can synthesise and breakdown.
Adipose only used fat
What is the brain specialised for?
Mainly uses glucose and can use ketone bodies
What are the only organs that store fuel?
Muscle (resting) = glycogen
Adipose tissue = TAG’s
Liver = glycogen
What organs use fatty acids as their preferred fuel?
Everything but the brain
What is the preferred fuel of the brain?
Glucose and ketone bodies
What organs will use any fuel?
Exercising skeletal muscle and the liver
What organs do not export fuels?
Brain, skeletal muscle resting and heart muscle
What does skeletal muscle during exercise export?
Lactate and alanine
What does adipose tissue export?
Fatty acids and glycerol
What does the liver export?
TAGS (VLDL), glucose, ketone bodies
What happens to nitrogen during starvation?
Urinary ammonia increases and then plateaus, total urinary nitrogen decreases
What is the source of glucose in the first 4 hours of starvation?
Use circulating glucose
What is the source of glucose after a day or two of starvation?
Glycogen stores - in both muscle and liver (liver store lasts a lot longer)
What happens after multiple days?
The main source is from glucose that is being made mostly in the liver and also the kidney - glycogenesis
What happens to total nitrogen excretion during starvation?
Decreased
What happens to urea during starvation?
Decreases - starts off well maintain, then drops off because urea cycle requires ATP
What happens to ammonia during starvation?
Increases
Why does ammonia increase during starvation?
It is more energy efficient to excrete nitrogen as ammonia through the kidneys than it is to be making urea in the liver
What happens to uric acid and creatinine during starvation?
Maintained
Under starvation mode there is a huge utilisation of?
Fatty acids
Increased fatty acid mobilisation causes the generation of a lot of?
Acetyl CoA - this drives ketone bodies production
What can be used to make glucose in the liver?
Pyruvate or lactate
How does muscle aid in the liver making glucose?
Can provide alanine to the liver to get converted into pyruvate and then glucose
How does the muscle aid in making ketone bodies?
release glutamine to the kidney, and via its metabolism make ketone bodies
What is driving these huge changes (our tissues to switch in their utilization and production of fuels)?
Mainly glucagon as well as cortisol and adrenaline
How does glucagon aid in the starvation response?
It increases and decreases activity of many different enzymes - Therefore it can drive most of what is going on
What is adrenaline and cortisol secreted by?
Adrenal glands
How do adrenaline and cortisol aid in the starvation response?
Binding to their receptors and generating downstream effects
How is fat metabolism regulated?
By glucagon
How does glucagon regulate fat metabolism?
By inhibiting lipogenesis
How is lipogenesis inhibited?
Because glucagon inhibits the enzyme Acetyl CoA carboxylase
What is the role of the enzyme Acetyl CoA carboxylase?
Converts Acetyl-CoA into malonyl CoA
Why do we want to inhibit fat metabolism during starvation?
- you don’t want fats being synthesized you want them being utilized for fuel
- allows more acetyl coa to make ketone bodies in the mitochondria
What does the ability to make ketones depend on?
Age - newborns make ketones early on compared to adults because they have a reduced ability to make new glucose
Other than age, what factor also contributes to increased ketone production?
Pregnancy and lactation due to increased glucose requirements
What is ketone body concentration in fed state?
< 0.1mmol/L
What is ketone body concentration in fasted state?
0.3mmol/L
What is ketone body concentration in starved state?
10mmol/L
What is ketone body concentration in newborn babies?
2-3mmol/L
What is ketone body concentrations in type 1 diabetes and ketoacidosis?
> 30mmol/L
