Changes to metabolism Flashcards
What is the difference between essential and non essential amino acids?
Essential= Cannot be produced by the body, have to be obtained externally. eg. through the diet
Non essential= Can be produced by the body
How many amino acids are there in total?
20 amino acids.
Alanine–>pyruvate
How does alanine lose its amino acid group? What does this form and what is it catalysed by?
- Alanine loses its amino group by transamination
-Forms pyruvate, catalysed by alanine aminotransferase
Asparagine —> Oxaloacetate
Asparagine is hydrolysed by what? and what does this liberate?
- Asparagine is hydrolysed by asparaginase
- Liberating ammonia and aspartate
Asparagine —> Oxaloacetate
Aspartate loses its amino group by transamination via what enzyme? And what does this form?
-Aspartate aminotransferase
-Forms oxaloacetate
Glutamine —> alpha-Ketoglutarate
What two things is glutamine converted to? And by what enzyme?
- Glutamate
- Ammonia
-By the enzyme glutaminase
Glutamate is converted to -ketoglutarate by oxidative deamination by glutamate dehydrogenase (1).
Glutamine —> alpha-Ketoglutarate
What is glutamate converted to? and by what?
- Glutamate is converted to alpha-ketoglutarate
- By oxidative deamination by glutamate dehydrogenase
Tyrosine—>Fumarate is what type of reaction?
A multi-step reaction
Tyrosine—>Fumarate:
What are the 4 stages of this reaction?
- Transamination
- Dioxygenation
- Isomerisation
- Hydrolysis
Tyrosine—>Fumarate:
Transamination:
What 2 reactions occur during this stage?
- Tyrosine —> Hydroxy-phenylpyruvate
- ⍺-ketoglutarate—>Glutamate
Tyrosine—>Fumarate:
Dioxygenation:
What 3 reactions occur during this stage?
- Hydroxy-phenylpyruvate—> Homogentisate
- O2 + Ascorbate (Vitamin C)—> CO2 + H2O
- Homogentisate —> 4-Maleylacoacetate
Tyrosine—>Fumarate:
Isomerisation:
What reaction occurs during this step?
4-Maleylacoacetate—> 4-Furmarlacoacetate
Tyrosine—>Fumarate:
Hydrolysis:
What reaction occurs during this step?
4-Furmarlacoacetate—> Fumarate and Acetoacetate
What are 3 main causes of starvation?
- Inability to obtain food
- Desire to lose weight
- Clinical Situations: eg. Trauma (shock), Burns, Injury to face, Tumour
What happens at a metabolic level during starvation:
What are the 2 main things that occur at a metabolic level during starvation?
- Blood levels of amino acids, glucose, and triacylglycerols fall
- Blood insulin levels are very low, glucagon levels are very high
What happens at a metabolic level during starvation:
- Blood levels of amino acids, glucose, and triacylglycerols fall
- Blood insulin levels are very low, glucagon levels are very high
Both these factors trigger a period of what? and this is characterised by the degradation of what 3 things?
- Trigger a period of catabolism
- Characterised by the degradation of:
- Glycogen —> Glucose
- Triacylglycerol —> Fatty Acids and Glycerol
- Protein —> Amino Acids
What happens at a metabolic level during starvation:
The degradation of the previous 3 things results in what?
Results in an interchange of substrates between:
Liver, Adipose tissue, Skeletal Muscle, Brain
What determines the fate of these substrates:
The fate of these substrates is determined by 2 crucial factors: What are they?
- The essential need to conserve glucose for cells &tissues that really need it. eg. red blood cells and brain.
- The need to mobilise fatty acids from adipose tissue andketone bodies from liver. To supply energy to all othertissues, and for these other tissues to adapt to these non-glucose substrates
Enzymatic changes in starvation:
In all situations the flow of intermediates through biochemical pathways is controlled by 4 mechanisms:
What are they?
- Availability of substrates
- Allosteric activation/inhibition of enzymes
- Covalent modification of enzymes
- Reciprocal Induction or repression of enzyme synthesis
The Liver in Starvation: Carbohydrate Metabolism
Glycogen is broken down then gluconeogenesis occurs, what objectives does this meet?
- Maintain blood glucose levels
- Sustain energy provision for the brain and other glucose requiring tissues (e.g. red blood cells).
The Liver in Starvation: Carbohydrate Metabolism
Increased glycogen degradation
What is the major source of blood sugar after a meal?
Glucose from food
The Liver in Starvation: Carbohydrate Metabolism
Increased glycogen degradation
A few hours after a meal, What starts to decline?
Blood glucose levels start to decline
The Liver in Starvation: Carbohydrate Metabolism
Increased glycogen degradation
Insulin levels drop and glucagon levels increase: what does this stimulate?
Liver glycogen stores will last for 10-18 hours of fasting.
Stimulates glycogen breakdown in liver (by cAMP cascade)
The Liver in Starvation: Carbohydrate Metabolism
Increased glycogen degradation
How long will liver glycogen stores last whilst fasting?
10-18 hours
The Liver in Starvation: Carbohydrate Metabolism
Increased gluconeogenesis
What does the liver have the unique ability to do that is vital during starvation?
- Unique ability of liver to synthesise glucose
- Becomes increasingly active as glycogen stores are depleted
The Liver in Starvation: Carbohydrate Metabolism
Increased gluconeogenesis
Where are carbon skeletons derived from?
- Glycerol
- Lactate
- Amino acids
The Liver in Starvation: Lipid Metabolism
this results in an increased oxidation of what?
Increased fatty acid oxidation
The Liver in Starvation: Lipid Metabolism
What is a major source of energy for liver during starvation?
Oxidation of fatty acids derived from adipose tissue (this spares glucose)
The Liver in Starvation: Lipid Metabolism
There is an increased synthesis of what during lipid metabolism?
Increased synthesis of ketone bodies
The Liver in Starvation: Lipid Metabolism
Ability of the liver to synthesise and release ketone bodies is describes as what?
Unique
The Liver in Starvation: Lipid Metabolism
When is the synthesis of ketone bodies favoured?
- When the concentration of acetyl CoA that is produced (via fatty acid oxidation), exceeds the maximal rate of the citrate cycle
The Liver in Starvation: Lipid Metabolism
Why are ketone bodies vital in starvation?
- Because they can be used by other tissues and cells, provided they have mitochondria
The Liver in Starvation: Lipid Metabolism
Once the level of ketone bodies in the blood is high enough, how much of the brain can use them as fuel?
- Up to ⅔ of the brain can use them as fuel
The Liver in Starvation: Lipid Metabolism
Utilisation of ketone bodies reduces the need for what?
- Reduces the need for amino acid precursors used in gluconeogenesis
- This decreases protein breakdown
Adipose Tissue in Starvation: Carbohydrate Metabolism
in starvation, insulin levels do what? and how does this effect the use of glucose for fatty acid synthesis?
- In starvation, insulin levels decrease
- So glucose is not used for fatty acid synthesis (no signal).
Adipose Tissue in Starvation: Lipid Metabolism
Increased degradation of triglycerides results in what?
- Decrease in insulin
- Increase in glucagon (via cAMP cascade)
- This causes phosphorylation and activation of hormone-sensitive lipase
Adipose Tissue in Starvation: Lipid Metabolism
There is an increase in the release of fatty acids during this process, how does this occur?
- Fatty acids obtained from the hydrolysis of stored adipose triglycerides are released into the bloodstream
Adipose Tissue in Starvation: Lipid Metabolism
There is an increase in the release of fatty acids:
What do they bind to? and what is there main function after binding?
- Bound to albumin
- They are transported to lots of tissues for use as a fuel
Adipose Tissue in Starvation: Lipid Metabolism
There is an increase in the release of fatty acids: Fill in the blanks:
The glycerol that is produced as the result of ——– ———- ——– is used for ———- by the ——-.
The glycerol that is produced as the result of COMPLETE TRIGLYCERIDE HYDROLYSIS is used for GLUCONEOGENISIS by the LIVER.
