Lecture 34: Coordinating Metabolism - Starvation Flashcards
What are the concepts for energy homeostasis under starvation?
- Maintenance of blood glucose levels to preserve brain
function. - Sparing of glucose by multiple tissues.
- Making alternative fuels available.
- Provision of special fuel needs of each tissue.
- Sparing of structural body proteins
What happens to fuel levels in blood during starvation for ketones, glucose, FFAs and Protein usage?
Ketone production ramped up
Glucose levels maintained
Increase in FFAs
Protein utilised initially then conserved
What two fuel sources can the brain use during starvation?
Glucose
Brain can also utilise ketone bodies
What are the intertissue relationships during starvation?
New glucose is made in the liver from gluconeogenic
precursors i.e. glycerol from fat (adipose) and pyruvate from alanine (muscle).
Mobilisation of fat from adipose.
Influx of FFAs into liver and subsequent B-oxidation increases acetyl CoA which drives ketogenesis
Ketone bodies provide acetyl coA for TCA (CAC) cycle and
ATP generation in brain and muscle.
What hormone is responsible for the metabolic adaptations that take place during starvation?
These metabolic adaptions are driven by glucagon in response to low glucose and potentiated (made more effective/active) by cortisol and adrenaline.
Describe starvation metabolism in a general sense:
Gluconeogenesis in liver prominent.
Fat becomes a prominent fuel for many tissues.
Ketones made in liver from catabolism of fat becomes
alternative and efficient fuel for brain (also serves to
spare glucose).
Mobilisation of muscle protein is spared.
What transcription factor activates gluconeogenic genes?
FoxO1 is a transcription factor that activates gluconeogenic genes. (in the liver)
Where does gluconeogenesis mainly occur? What molecules can this glucose be made from? What provides the energy for these reactions?
- Occurs mainly in liver (some in kidney).
- Synthesis of glucose from:
– lactate from Rbcs and muscle
– alanine from muscle protein
– glycerol from adipose tissue - Stimulated by glucagon.
- Fatty acid oxidation provides the energy and reducing
power. - Brain uses most of the glucose.
How does alcohol effect gluconeogenesis? How many NADH are produced from 1 molecule of alcohol?
It inhibits gluconeogenesis:
For every molecule of alcohol, two molecules of NADH are produced.
This increases the NADH to NAD+ ratio And drives gluconeogenic precursors away from gluconeogenesis:
* Pyruvate to lactate
* Oxaloacetate to malate (see TCA cycle)
This inhibits gluconeogenesis, lowers blood glucose, lowers pH and can eventually cause a coma.
Who would be expected to survive longer under
starvation?
1. An obese person
2. A body builder
3. A normal weight person
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Where are ketone bodies synthesised and what from?
Synthesised in the liver from fatty acids.
Used by starving brain as energy source
What molecule provides the substrate to synthesise ketone bodies?
Acetyl-CoA, which is primarily derived from the breakdown of fatty acids through beta-oxidation.
What is ketogenesis and what are its steps?
Ketogenesis is the liver’s process of converting excess acetyl-CoA into ketone bodies during low glucose availability.
Steps:
1.Fatty acid breakdown → Produces acetyl-CoA via beta-oxidation.
- Excess acetyl-CoA accumulates when the TCA cycle is limited.
- Acetyl-CoA is converted into acetoacetate.
- Acetoacetate can be reduced to beta-hydroxybutyrate
- Ketone bodies (acetoacetate and beta-hydroxybutyrate (most use in starving brain)) are released into the bloodstream for energy use by other tissues.
