Lecture 34 - Coordinating Metabolism: Starvation Flashcards
What are key concepts of energy homeostasis under starvation?
- Maintenance of blood glucose for brain function
- Less glucose use in multiple tissues
- Alternative fuels
- Provision of special fuel needs of each tissue
- Sparing of structural body proteins
How much glycogen is stored in the liver?
~100 g
How much glucose does the brain need per day?
~120 g
How much energy is stored in 15 kg’s of TAG?
590000kJ
How many days could you survive for using only energy from TAG assuming 10000kJ per day?
59 days
What happened to the subjects in the Minnesota starvation experiment (1944)?
The men lost fat and muscle, were tired and became very irritable but recovered on refeeding.
What was the Minnesota starvation experiment (1944)?
Study conducted by Dr Ancel Keys on 36 men to study the physiological effect of starvation i.e.calorie intake halved for 6 months
What happens to fuel levels in blood during starvation?
- Ketone production ramped up
- Glucose levels maintained
- Increase in FFAs
- Protein utilised initially then conserved
What can the brain utilise as an alternative to glucose?
Ketone bodies
Origin of blood glucose stage I of fed to starving?
Exogenous
Origin of blood glucose stage II of fed to starving?
Glycogen, Hepatic gluco-neogenesis
Origin of blood glucose stage III of fed to starving?
Hepatic gluconeogenesis, Glycogen
Origin of blood glucose stage IV of fed to starving?
Gluconeogenesis hepatic and renal
Origin of blood glucose stage V of fed to starving?
Gluconeogenesis hepatic and renal
In which stages of from fed to starving is glucose the major fuel of the brain?
Stage I - Stage III
What are the major fuels of the brain in stage IV and V?
Ketone bodies + Glucose
What tissues are using glucose in stage I of fed to starving?
All
What tissues are using glucose in stage II of fed to starving?
All except - liver, muscle and adipose at diminished rates
What tissues are using glucose in stage III of fed to starving?
All except liver, muscle and adipose tissue at rates intermediate between II and IV
What tissues are using glucose in stage IV of fed to starving?
Brain, RBCs, renal medulla, small amount by muscle
What tissues are using glucose in stage V of fed to starving?
Brain at diminished rate, RBCs, Renal medulla
What can new glucose be made from in the liver?
Gluconeogenic precursors
What does mobilisation of fat from adipose do?
Creates an influx of FFAs into the liver
What does an influx of FFAs into the liver cause?
B-oxidation which increases
acetyl CoA which
drives ketogenesis.
What do ketone bodies provide?
Acetyl CoA for TCA cycle and ATP generation in brain and muscle.
What drives the intertissue relationships during starvation?
Glucagon in response to low glucose and potentiated by cortisol and adrenaline
What happens in the starvation metabolism?
- 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 hormone activates gluconeogenesis?
Glucagon
What is FoxO1?
A transcription factor that activates gluconeogenic genes.
Are are some enzymatic reactions in metabolism reversible?
Yes many
Are reversible enzymatic reactions catalysed by the same enzyme?
Sometimes, however some enzymes require different enzymes to go in one direction or the other
Where does gluconeogenesis mainly occur?
The liver, some in kidney
What can glucose be synthesised from in gluconeogenesis?
– lactate from Rbcs and muscle
– alanine from muscle protein
– glycerol from adipose tissue
What provides the energy + reducing power for gluconeogenesis?
Fatty acid oxidation
What uses most of the glucose from gluconeogenesis?
The brain
What does alcohol inhibit?
Gluconeogenesis
How many molecules of NADH are produced for every molecule of alcohol metabolized?
Two molecules of NADH.
What effect does alcohol have on the NADH/NAD+ ratio?
It increases the NADH to NAD+ ratio.
Which gluconeogenic precursors are driven away from gluconeogenesis due to high NADH levels?
- Pyruvate is converted to lactate.
- Oxaloacetate is converted to malate.
What are the consequences of alcohol inhibiting gluconeogenesis?
It lowers blood glucose, lowers pH, and can lead to coma.
Why should you avoid drinking alcohol, especially in starvation mode?
Drinking alcohol in starvation mode can inhibit gluconeogenesis, leading to low blood glucose and impaired brain function.
How are ketone bodies synthesised?
In the liver from fatty acids
What does a starving brain use as an energy source?
Ketone bodies
Ketone body concentrations in the fed state?
< 0.1 mmol/L
Ketone body concentration in fasted state?
0.3 mmol/L
Ketone body concentration in starved state?
10 mmol/L
Type 1 diabetes ketoacidosis ketone body concentration?
> 30 mmol/L
