Lecture 6: Starvation Flashcards
What are the fuel stores of carbohydrates?
There are stores of carbohydrate in many different tissues.
• There are 12g in the blood.
• We need to use glycogen to supply the tissues.
• In muscle it can’t be liberated as glucose. There is no G6Pase. It is instead liberated as lactate, ala and pyr, which can be converted into glucose.
• In the liver it can be exported. This is enough to sustain the brain for 24 hours.
What are the fuel stores of fats?
The fuel stores of fats are much more extensive.
• Fats make up around 15-30% of our body weights. This translates to about 10-20kg.
• This is 50 days of energy.
• Fats cannot be used to make glucose.
• They can be used to make glycerol for GNG, however this supplies a small amount of energy.
What are the fuel stores of amino acids?
Amino acids can be used for GNG.
• They make up around 20% of the body weight (10-15kg).
• They can be oxidised or converted.
• The actual yield is lower than expected due to the urea cycle (4 ATPs are required to form urea).
• We can’t use all of it, only ½ of muscle protein.
How does fuel storage change over time?
We use different molecules as fuels as the amount of time spent in the starved state increases.
• Free glucose lasts about 30 minutes.
• Glycogen lasts about 18 hours.
• TAGs last about55 days.
• Protein lasts about 21 days.
• These are all based on a 10 MJ/day expenditure.
There are 5 different stages.
I: Glucose is used as the major brain fuel.
II: Post absorptive state. Blood glucose is down to 4-4.5 mM. Insulin concentration decreases. As per the Randle cycle FA mobilisation, GNG and glycogenolysis all occur. Glucose is still the major brain fuel.
III: Gluconeogenic phase until day 2-3. Liver glycogen becomes depleted so GNG from amino acids is used as the brain fuel. This would require 150g of muscle per day, so the body adapts with protein sparing mechanisms.
IV/V: Glucose and ketone bodies are the major brain fuel.
How does the body adapt? Draw a diagram.
The body undergoes many adaptions to starvation.
• After 2-3 days, liver glycogen is depleted.
• Ketogenesis, GNG and lipolysis all increase.
• Insulin is downregulated. This leads to a downregulation of leptin as well.
• Blood NEFA increases, it is the preferred fuel source.
• In liver esterification is downregulated. β oxidation and ketogenesis are upregulated.
• By week 4 KB concentration is 6 mM. It makes up for 2/3 of the oxygen consumption in the brain.
• Amino acid gluconeogenesis is downregulated as lactate from RBCs is recycled using energy from fats.
What are muscle sparing mechanisms?
The body wants to prevent too much protein from being degraded.
• In a fed state, amino acids and proteins can represent 2-% of oxidative metabolism.
• Protein could be a significant energy store but it has a function unlike fat and glycogen.
• During starvation, proteolysis occurs in skeletal muscle as it is less vital than other organs. It represents 40% of the protein in the body.
• With less insulin, we would expect proteolysis to be greater. However, this is prevented.
How are muscle sparing mechanisms controlled?
There are 2 ways in which muscle sparing mechanisms are controlled.
Hormonal control with T3
• Triiodothyronine (T3) is a hormone produced by the thyroid (as a T4 precursor). It the basal metabolic rate of all energy sources (including protein) in order to promote growth turnover).
• During starvation, formation of reverse T3 is favoured (from T4) over T3 by removal of an iodine atom.
• Reverse T3 decrease proteolysis rate while increase FA oxidation and mobilisation rate stays high in order to meet the body’s energy demands.
Hormonal control with adrenaline
• Adrenaline has an anabolic effect on muscle. Proteolysis is downregulated.
How are ketone bodies produced?
- Fat stores are much larger than glycogen or protein stores.
- Ketone bodies supply 70% of the brain’s energy during prolonged starvation.
How does kidney metabolism work?
The kidney plays an important role in metabolic integration.
• An increase in NEFA and KB concentration can cause acidosis.
• The protons need to be secreted. They are excreted via urea.
• The kidney takes up glutamine and makes ammonia from glutaminase (kidney isoform is upregulated during acidosis) and glutamate dehydrogenase.
• The carbon skeleton (α-KG) is then fed into renal gluconeogenesis.
• This can make up to 50% of GNG.
