Protein Metabolism Flashcards
What is the use of amino acids in the body?
- Protein synthesis
- Synthesis of nitrogen containing metabolites
- Energy (ATP)
- Fatty acids, ketone bodies
- Glucose/glycogen
What nitrogen containing compounds can these amino acids be turned into:
- Glycine
- Tyrosine
- Tryptophan
- Histidine
- Glycine/arginine
- Glycine, aspartate, glutamine
- Haem
- Dopamine, noradrenalin, adrenalin (catecholamines)
- Serotonin
- Histamine
- Creatine
- Purine bases
What are the signs and symptoms of malnutrition?
- Poor growth
- Susceptibility to infection
- Changes in hair/skin colour
- Poor skin condition and poor nutrient absorption
- Abdominal bloating
- Lower limb oedema
How does a lack of protein lead to susceptibility to infection?
Antibodies are proteins
How does a lack of protein lead to poor growth?
Need protein for DNA, ATP etc
How does a lack of protein lead to changes in hair/skin colour?
Insufficient melanin
How does a lack of protein lead to poor skin condition and poor nutrient absorption?
Epithelial cells have high turnover rate –> inability to replace leads to poor condition of skin
Epithelial cells also line gut, leading to problems with absorption
How does a lack of protein lead to lower limb oedema?
Lack of albumin (blood protein) –> fluid is retained and oedema occurs
How does a lack of protein lead to abdominal bloating?
Reduced albumin due to protein deficiency –> fluid accumulates in tissues, causing build up in abdomen
Accumulation of fat in liver
If amino acids are not required for synthetic reactions, what can they be used for? What must occur for this to happen?
Used for energy, or converted to energy storage compounds
Amino group must be removed and nitrogen excreted
Why must blood ammonia levels be kept low?
Ammonia is very toxic
What can hyperammonaemia lead to?
Tremor, vomiting, cerebral oedema, coma, death
What can hyperammonaemia be caused by?
Genetic defects (e.g. deficiencies of urea cycle enzymes)
More commonly caused by liver disease (hepatitis or cirrhosis)
How is ammonia excreted?
Converted to urea for excretion by the kidneys
What are the 3 steps in the excretion of urea?
- Transamination
- Deamination
- Urea synthesis
What is step 1 - transamination?
Transfer of amino group from amino acid to a-ketoglutarate to form glutamate (in most tissues)
What is step 2 - deamination?
Release of ammonia from glutamate (reverse)
Where does step 2 - deamination - mainly happen?
Liver
What is step 3 - urea synthesis?
Urea cycle (in liver)
How can ammonia be safely transported to the liver?
As glutamate or glutamine
What does step 1 (transamination) require?
Pyridoxal phosphate
What is pyridoxal phosphate?
The active form of vitamin B6
What can a lack of vitamin B6 lead to?
- Anaemia (lack of haem)
- Neurological symptoms (lack of neurotransmitter and lipid synthesis)
- Poor growth, skin lesions, poor immune responses (lack of protein synthesis)
What is vitamin B6 required for?
- Transamination and synthesis of non-essential amino acids
- Decarboxylation reactions required for neurotransmitter synthesis
- Haem synthesis
- Some aspects of energy metabolism & lipid synthesis
What is the control step in urea synthesis?
Carbamoyl phosphate synthesis
What synthesises carbamoyl phosphate? What is this enzymes activated by?
Carbamoyl phosphate synthetase 1
Is allosterically activated by N-acetylglutamate
When is N-acetylglutamate formed?
When glutamate levels are high
What does high glutamate levels signal?
High levels of protein catabolism
What is the speed of the urea cycle determined by?
The amount of amino acids (activated by high levels of amino acids)
Where does the urea cycle take place?
Partly in the mitochondrial matrix and partly in the cytosol
Describe the urea cycle inside the mitochondrial matrix
- Carbamoyl phosphate formed from ammonia and bicarbonate – control step
- Carbamoyl group transferred to ornithine to form citrulline
Describe the urea cycle in the cytosol
- Second amino group added from aspartate
- Arganine formed and hydrolysed
- Urea released
What does uric acid contain?
Nitrogen
What is uric acid derived from?
Purine nucleotides rather than proteins
What is excess uric acid in the blood called?
Hyperuricaemia
What can hyperuricaemia lead to?
Deposition of sodium urate crystals in the kidneys and in the joints
What are deposits of sodium urate crystals in the kidneys called?
Kidney stones
What are deposits of sodium urate crystals in the joints called?
Gout
What is hyperuricaemia caused by?
Over-production of urate, or poor excretion via the kidneys
What are high purine foods?
Red meat, seafood, yeast-containing foods
What can the carbon skeleton of amino acids be fed into?
Several metabolic pathways:
- Krebs cycle (used to synthesis ATP)
- Fatty acid and ketone synthesis
- Glucose synthesis (gluconeogenesis)
What amino acids cannot be made into glucose? Why?
Lycine and Leucine
Only enter the cycle via acetyl CoA
Describe Lycine and Leucine
Solely ketogenic –> can only be made into Acetyl CoA and ketone bodies
What are glucogenic amino acids?
Can be degraded to glucose precursors
What are ketogenic amino acids?
Can be degraded to precursors of fatty acids and ketone bodies
Can acetyl CoA be converted to glucose?
No
What is gluconeogenesis?
Making glucose from non-carbohydrate intermediates (during fasting or exercise)
Where does gluconeogenesis mainly take place?
In the cytosol of the liver and kidney
Gluconeogenesis takes place from what precursors?
- Keto acids (derived from amino acids particularly alanine)
- Lactate (from anaerobic glycolysis)
- Glycerol (from triacylglycerol breakdown)
What is gluconeogenesis vital for?
Maintaining blood glucose levels as glycogen stores only last about 18 hours
Gluconeogenesis is mainly a reversal of glycolysis (but there are 3 irreversible steps in glycolysis, therefore different enzymes are required for reversal).
What 3 steps in gluconeogenesis are catalysed by different enzymes to glycolysis?
- Pyruvate –> phosphoenolpyruvate (requires several stages)
- Fructose 1,6 bisphosphate –> fructose 6 phosphate (fructose 1,6 bisphosphatase)
- Glucose 6 phosphate –> glucose (glucose 6 phosphatase)
How is gluconeogenesis and glycolysis controlled?
- High glucose and/or low energy = glycolysis
- Low glucose and/or high energy = gluconeogenesis
What is glycolysis activated by?
AMP, ADP (suggests low energy)
Insulin
What is glycolysis inhibited by?
ATP
Glucagon
What is gluconeogenesis activated by?
Citrate
Glucagon
Acetyl CoA
What is glyconeogenesis inhibited by?
AMP, ADP (suggests low energy)
Insulin
What is not produced in type 1 diabetes?
Insulin
What is effect of type 1 diabetes on glycolysis?
Glycolysis is inhibited (insulin is also required to allow glucose entry to muscle and adipose tissue)
Blood glucose levels rise
Where is insulin released from?
Pancreas
What is effect of type 1 diabetes on gluconeogenesis?
Is stimulated –> the liver synthesises and releases glucose into the circulation
Blood glucose levels rise further
In type 1 diabetes, in order to provide substrates for gluconeogenesis, what happens?
Muscle protein is broken down to provide amino acids –> rapid weight loss
Describe function of liver during exercise
- Anaerobic respiration
- Lactate production
- Lactate removed (so glycolysis can continue)
- Lactate travels to liver
- Lactate converted back into glucose by gluconeogenesis which can then be released again for muscles
Why does alcohol make you hungry?
- Ethanol is metabolised in the liver
- Produces large amounts of NADH so lowers levels of NAD+
- NADH inhibits gluconeogenesis and lowers blood glucose (hungry)
Pyruvate and alanine is converted to lactate instead of glucose in presence of lots of NADH
Alanine –> pyruvate –> lactate
