MEH - Protein and amino acid metabolism Flashcards
Name 4 important nitrogen containing compounds in the body
Proteins
Amino acids
RNA/DNA
Creatine
What is creatinine and what is it used for clinically (2)?
Breakdown of creatine and phosphocreatine in muscle.
Usually excreted at a constant rate - is proportional to muscle mass so can be used to estimate muscle mass
Also indicator of renal function (raised level on damage to nephrons)
What are the normal figures for nitrogen balance in 70Kg man? What is the amino acid pool in the body?
16g in via diet
2g out via hair skin nails
14g out via urine and faeces
16g amino acid pool
Is a negative nitrogen balance normal? What are some causes?
Never normal
Causes e.g. infection, malnutrition, trauma
What part of protein metabolism is a potential source of ammonia?
Removal of the amino group - ammonia quickly converted to urea which isn’t toxic
Ammonium ions are also toxic
Name a glucogenic, ketogenic amino acid and one that does both
1) Glucogenic - Alanine
2) Ketogenic - Lycine
3) Both - Tryptophan
When does AA mobilisation occur? How is it regulated?
During extreme starvation
Under hormonal control:
Insulin/growth hormone - decrease mobilisation and increase protein synthesis
Cortisol - increase mobilisation and decrease protein synthesis
How can Cushing’s syndrome lead to striae?
Excess cortisol
Excess protein breakdown
Weakens skin structure - striae
What are the 9 essential AAs? If Learnt This Huge List May Prove Truly Valuable
Isoleucine Lysine Threonine Histidine Leucine Methionine Phenylalanine Tryptophan Valine
Which amino acids are conditionally essential and what does this mean?
Arginine
Tyrosine
Cysteine
In pregnancy/children these may become essential so will need to be supplemented from the diet
Non-essential amino acids can be synthesised - Where does the carbon skeleton come from for this (3)? Where does the amino group come from (2)?
Can come from:
Glycolysis intermediates (C3) Pentose phosphate pathway (C4 & C5) Krebs Cycle (C4 & C5)
Amino group comes from transamination from another amino acid - or from ammonia.
What is hydrogen sulphide and what is the relevance of amino acids in relation to it?
It is a signalling molecule that requires specific amino acids in it’s synthesis
What other types of compounds require amino acids for their synthesis?
- Some neurotransmitters - GABA, 5-HT
- Hormones - e.g. thyroid
- Signalling molecules - NO
What part of the amino acid is used in oxidative metabolism and how?
The carbon skeleton
- Removal of amino group
- Carbon skeleton will then go onto make ketones or glucose to then go onto stage 3 and 4 metabolism (TCA cycle and ETC)
What is the most common amino acid formed from transamination? From what intermediate (ketoacid).
Glutamate from alpha-ketoglutarate
Which amino acid is the exception and what does it form/via which intermediate (ketoacid)?
Aspartate aminotransferase used oxaloacetate and forms aspartate
What is pyridoxal phosphate? From which B vitamin is it derived?
It is a coenzyme that is required for all aminotransferases. It is a derivative of vitamin B6.
What are ALT and AST and their roles?
Alanine Aminotransferase - converts alanine to glutamate
Aspartate aminotransferase - converts glutamate to aspartate.
When are ALT and AST used clinically and what do they indicate?
Used to show liver damage - levels are particularly high in liver necrosis e.g. viral hepatitis, autoimmune liver diseases, toxic injury (e.g. alcohol).
In deamination - what needs to occur immediately after and why? What does a deaminised amino acid become?
Urea cycle - to prevent toxic effects of ammonia
A ketoacid
Which three enzymes deaminate amino acids from the lecture?
Amino acid oxidases
Glutaminases
Glutamate dehydrogenase
What other role does urea play apart from ammonia?
Osmotic role in kidney tubules
Where does the urea cycle occur? How many enzymes?
In the liver - 5 enzymes
What happens in refeeding syndrome? What are the risk factors?
Urea cycle is down regulated so increasing protein intake rapidly will lead to ammonia toxicity. Risk factors are BMI <16, Unintentional weight loss >15% in 3-6months, 10days or more with little or no nutritional intake
What can happen with a defect in urea cycle enzymes? What symptoms? How do you manage these disorders?
Autosomal recessive disorders caused by deficiency in one or more enzymes of urea cycle. Can get hyperammonaemia, accumulation of urea cycle intermediates.
- Vomitting
- Lethargy
- Irritability
- Mental retardation
- Seizures
- Coma
- Death
Low protein diet, replace amino acids in diet with ketoacids
Why is ammonia so toxic?
Readily diffusible and toxic to brain
- Interferes with amino acid transport and protein synthesis
- Disruption of cerebral blood flow
- pH effects - alkalising
- Interferes with TCA cycle
- Interferes with metabolism of excitatory amino acid neurotransmitters
- Interferes with BBB
How is ammonia removed from tissues before being removed by the urea cycle or immediately excreted by kidney (2)? Which enzyme?
1) Glutamine - ammonia combines with glutamate to form glutamine - travels in blood to liver - reforms glutamate and ammonia by glutaminase - enters urea cycle
2) Alanine - ammonia combines with pyruvate to form alanine - transported to liver by blood where it is converted back to alanine by transamination - Amino group then fed into urea cycle for disposal, pyruvate can be used to synthesise glucose which can be fed back to tissues.
There are over 50 inherited diseases of involving defects in amino acid metabolism - what is the most common area of defect?
Enzymes - partial or total loss of function
What is PKU and what happens? What chromosome? Why is the urine musty? What is the treatment?
Phenylketonuria - deficiency in phenylalanine hydroxylase so can’t convert phenylalanine into tyrosine to make DA, NA, Adrenaline, Melanin, Thyroid hormone, protein synthesis.
Chromosome 12
Symptoms are developmental delay, severe intellectual disability, microcephaly, seizures, hypopigmentation
Accumulation of phenylketones in urine - musty smell
Treatment - low phenylalanine diet - avoid artificial sweeteners avoid high protein food like meat, milk, eggs
What are homocystinurias? Which enzyme defect? What is the treatment? What is elevated plasma homocysteine associated with?
Problem in the breakdown of methionine - defect in cystathionine beta-synthase.
Symptoms are connective tissue problems, muscles, CNS, CVS.
Treatment is low methionine diet avoid milk fish meat cheese eggs, nuts, peanut butter.
Supplement with cysteine, Vit B6, B12, betaine and folate.
Elevated homocysteine in plasma is associated with CVD
Where does transamination vs deamination occur in the body?
Transamination - widespread but mostly liver, skeletal muscle, cardiac muscle and kidney. Mainly liver?
Deamination - mainly liver and kidney
What can increase the amount of urea cycle enzymes?
Amount of ammonia needing to be disposed of
High protein diet
Is the urea cycle regulated?
No but it is inducible (by two things above) and suppressed by low protein diet
What two ways can ammonia be detoxified in the body?
Either via urea cycle in the liver
Or being used in the synthesis of N compounds e.g. glutamine (Ammonia+Glutatmate)
Why is glutamine at higher concentration than other amino acids in the body?
As it is converted from Ammonium + Glutamate to glutamine to be excreted
What is the difference between the liver and kidney in how they deal with ammonia?
Liver - urea cycle detoxifies ammonia by converting it to urea
Kidney - ammonia directly excreted into urine
What is thought to be one of the main features of ammonia toxicity?
The fact it combines with alpha-ketoglutarate to form glutamate and this removes alpha-ketoglutarate from the TCA cycle leading to less energy being made in CNS cells
