Protein And Amino Acid Metabolism Flashcards
What molecules contain Nitrogen?
- Amino Acids
- Proteins
- Purines + Pyrimidines (DNA/RNA)
- Porphyrins (haem)
- Creatine phosphate
- Neurotransmitters (eg dopamine)
- Some hormones (eg adrenaline)
What is creatine phosphate used for?
Used as an energy resource if doing high intensity exercise eg springting.
What is creatinine?
Creatinine is the breakdown product of cratine and creatine phosphate in muscles. It is usually produced at a constant rate (depending on muscle mass). It is filtered via kidneys.
What are the clinical uses of creatinine?
Creatinine used to estimate muscle mass. This is becuase creatinine excretion in urine over 24hrs is porportional to muscle mass.
Creatinine is also used as an indicator of renal function. (There is a raised level on damage to nephrons)
Where does nitrogen reside?
Most of our nitrogen resides in body proteins (2kgN).
It is also in Amino Acids (16g) and N-containing compounds (60g).
Our dietary protein intake is 16g per day.
How is nitrogen lost from the body?
- Skin, Hair, Nails (2g)
- N-waste products in faeces and urine (Urea). -14g.
When is there a positive or negative nitrogen balance in the body?
Positive N balance (when intake is bigger than output) occurs in pregnancy, in adults recovering from malnutrition or in growth.
Negative N balance is never normal. This occurs when there is a loss of body protein. This occurs in trauma, infection or malnutrition.
N equilibrium is the normal state in adults.
Whats add to the amino acid pool and what is used for?
Freon Dietary proteins in digestion and denovo amino acid synthesis add to the amino acid pool.
Free amino acids are then used in synthesis of cellular protein but proteolysis returns them.
How are free amino acids broken down?
Amino group makes urea to then be excreted in urine.
The Carbon skeleton used in Glucogenic and ketogenic amino acids. Glucogenic amino acids are used in gluconeogenesis and ketogenic amino acids are used in the synthesis of ketone bodies. But, they both make energy
What controls the mobilisation of protein reserves?
Hormones
When does the mobilisation of protein reserves occur?
Occurs during extreme stress (starvation)
How is fuel stored in a 70kg man?
Largest store is triacylglycerols (Insert table)
What disease is a result of excessive breakdown of proteins?
Cushing’s syndrome. This is excess cortisol which weakens skin structure and lead to striae formation. It promotes proteolysis.
What are the structure of amino acids?
These amino acids then join together via peptide bonds to form proteins.
If Learnt This Huge List May Prove Truly Valuable
What are the 9 essential amino acids?
- Isoleucine
- Lysine
- Threonine
- Histidine
- Leucine
- Methionine
- Phenylalanine
- Tryptophan
- Valine
If Learnt This Huge List May Prove Truly Valuable
What are the conditionally essential amino acids?
- Arginine
- Tyrosine
- Cysteine
These are the amino acids required in pregnant women and children because they have a high rate of protien synthesis.
What three places can the C atoms for non-essential amino acid synthesis come from?
- Intermediates of glycolysis
- Pentose phosphate pathway
- Krebs cycle
Where do the amino groups for the non essential amino acids come from?
Transammination or ammonia
Tyrosine is required for the synthesis of…
- Catecholamines,
- Melanin,
- Thyroid Hormones
Cysteine is required for the synthesis of…
- Hydrign Sulphide (gaseous signalling molecule),
- Glutathione
Tryptophan is required for the synthesis of…
- Nicotinamide
- Serotonin (5HT)
- Melatonin
Histidine is required for the synthesis of…
Histamine
Arginine is required for the synthesis of…
Nitric oxide
Glutamate is required for the synthesis of…
GABA
Serine is required for the synthesis of…
Sphingosine
Glycine is required for the synthesis of…
- Purine
- Glutathione
- Haem
- Creatine
How do you remove nitrogen from amino acids?
- Transamination
- Deamination
What is transamination?
This is when you swap an amine for an oxygen to produce a different amino acid and ketoacid.
Most aminotransferase enzymes use a-ketoglutarate to funnel the amino group to glutamate.
The exception to this rule is aspartate aminotransferase which uses oxyloacetate to funnel amino groups to aspartate.
All aminotransferases require the coenzyme pyridoxal phosphate which is a derivative of vitamin B6
What are the two key aminotransferase enzymes?
Alanine aminotransferase (ALT) - which converts alanine to glutamate
Aspirate aminotransferase (AST) - which converts glutamate to aspartate.
When are these enzymes (ALT/AST) high? And what test are they measured as part of?
Plasma ALT and AST levels are measured routinely as part of a liver function test.
The levels are particularly high in conditions that cause extensive cellular neucrosis such as:
- Viral Hepititis
- Anutoimmune Liver Disease
- Toxic Injury
What is deamination?
Deamination is the liberation of amino groups as free ammonia.
This mainly occurs in liver and kidney.
Keto acids can be utilised for energy.
Also important in deamination of dietary-D-aminoacids (fund in plants and microorganisms)
Ammonia and ions are very toxic and must be removed. They are ultimately, converted to Urea or excreted directly in urine.
What enzymes can deaminate amino acids?
- Amino acid oxidases
- Glutaminase
- Glutamate dehydrogenase.
What are some properties of Urea?
- High nitrogen content
- Non-toxic
- Extremely water soluble
- Chemically inert in humans as we dont have enzymes to break it down (bacterial do)
- Most Urea is excreted in urine via the kidneys
- Also performs useful osmotic role in kidney tubules.
Urea cycle?
The urea cycle occurs in the liver and involves 5 enzymes.
The amount of urea cycle enzymes normally related to the need to dispose of ammonia.
High protein diet induces enzyme levels.
Low protein diet or starvation represses levels.
The cycle in inducible but not regulated.
Aspartate and Glutamate feed into the cycle.
Urea comes out.
Needs CO2 and ATP (gets the from the mitochondria)
What is refeeding syndrome?
Giving a big meal to starving people can lead to death because the enzymes in the urea cycle are not present (or present in very low dose).
This, means ammonia can accumulate and lead to ammonia toxicity and death.
Need to refeed at 5 to 10 kcal/day and raise gradually to full need within a week.
What causes defects in the urea cycle?
Autosomal recessive genetic disorders cause deficiency of one of enzymes in the urea cycle.
Occur in 1 in 30,000 live births
Mutations can cause a partial loss if enzyme function whcih leads to:
- Hyperammonaemia
- accumulation / excretion of urea cycle intermediates.
What are the symptoms of urea cycle defects?
- Vomiting
- Lethargy
- Irritability
- Mental retardation
- Seizures
- Coma
What does the severity of urea cycle defects depend on and how is it controlled?
Severely depends on the nature of the defect and the amount of protein eaten.
Management involves a low protein diet and the replacement of amino aicds with keto acids.
Why is ammonia toxic?
It is readily diffusible and extremely toxic to the brain so blood levels need to be kept low.
Amminia is toxic because:
- It Interferes with amino acid transport and protein synthesis
- It disrupts cerebral blood flow
- pH effect (alkaline)
- It interferes with metabolism of excitatory amino acid neurotransmitters (eg glutamate and asparate)
- It alters the blood brain barrier
- it interferes with the TCA cycle by reacting with a-ketoglutarate to form glutamate
What are the two mechanisms used to transport Nitrogen?
Glutamine and Alanine
Glutamine:
Ammonia is combined with glutamate to form glutamine.
Glutamine is transported in blood to liver or kidneys where it is cleaved by glutaminase to reform glutamate and ammonia.
In liver ammonia fed into urea cycle. In kidney it is excreteddirectly into urine.
Alanine:
Amine groups are transfered to glutamate by transamination
Pyruvate then transaminated by glutamate to form alanine
Alanine transported in blood to liver where it is converted back to pyruvate by transamination
Amino group is fed via glutamate into urea cycle for disposal as urea whereas pyruvate is used to synthesise glucose which can be fed back to tissues.
What are the clinical problems of amino acid metabolism?
There are over 50 inherited dideases involving defects in amino acid metabolism.
There is either a total, or more commonly, a partial loss if enzyme activity.
Individually, each disease is rare. But, collectively they constitute a significant portion of paediatrc genetic diseases.
If untreated, they frequently lead to intellectual imparment.
Treatment involves restricting specific amino acids in the diet.
What is the heel prick test?
This is genetic screening that occurs at birth to screen for a panel of diseased.
This is used in sickle cell, cystic fibrosis and congenital hyperthyroidism.
It also screens for Inborn errors of metabolism:
- Phenylketoneurea (PKU)
- Maple syrup urine disease)
- Isovaleric acidaemia (IVA)
- Glutaric aciduria
- Homocystinuria
What is PKU?
Phenylketonuria.
It is caused by a deficiency in phenylalanine hydroxylase.
Accumulation of phenylalanine in tissue, plasma and urine.
Phenylketones in urine.
There is a characteristic musty smell.
What is the PKU inheritance pattern?
Autosomal recessive
-affected gene is on chromosome 12
What is the treatment for PKU?
- Strictly controlled low phenylalanine diet with tyrosine.
- Avoid artificial sweeteners (contains phenylalanine)
- Avoid high protein food such as meat, milk and eggs.
What are the symptoms of PKU if it is not detected early?
- Severe intellectual disability
- Developmental delay
- Microcephaly
- Seizures
- Hypopigmentation.
What are the affected pathways in PKU?
- Noradrenaline
- Adrenaline
- Dopamine
- Melanin
- Thyroid hormone
- Protein synthesis
What are homocystinurias?
Problems breaking down methionine.
Excess Homocystine (which is the oxidised form of homosysteine) excreted in urine
Defect in cystathionine B-synthase is most common
It affects connective tissue, muscles, CNS, CVS
What are the inheritance patterns of homocystinurias?
Autosomal recessive.
Incidence of 1 in 344,000
What are the treatments for homosystinuras?
Low methionine diet
Avoid milk, meat, fish, cheese, eggs
Nuts and peanut butter also contain methionine
Cysteine, Vitamin B6, Betaine, B12, and Folate supplement
What is elevated homocysteine in the plasma associated with?
Cardiovascular disease
