Protein and Amino Acid Metabolism Flashcards
What are the main nitrogen-containing compounds in our body?
- Amino acids
- Proteins
- Purines + Pyramidines
In which compounds is nitrogen found in small amounts?
- Porphyrins (haem)
- Creatine phosphate
- Neurotransmitters (dopamine)
- Some hormones (adrenaline)
What percentage of our body’s mass is nitrogen?
~3%
What is creatinine?
- Nitrogen-containing breakdown product of creatine and creatine phosphate
- creatine phosphate is an immediate source of ATP in skeletal muscles (used at the start of a sprint)
- Produced at a constant rate depending on muscle mass
- amount of creatinine present in pts urine (over 24hrs) can give an indication of muscle mass
- not a constant rate when muscle is wasting
- Filtered by the kidneys into the urine
- Can be used to determine renal function
- high creatinine = damage to nephrons (particularly in elderly)
What are the reference ranges of creatinine excreted in the urine per day?
Men = 14-26 mg/kg
Women = 11-20 mg/kg
What is nitrogen balance?
Nitrogen input - nitrogen output = nitrogen balance
N equilibrium:
- intake = output
- no change to normal body protein
- normal state in an adult
Positive N balance:
- intake > output
- increase in total body protein
- normal state of growth (children and adolescents) and pregnancy
- normal in an adult recovering from malnutrition
Negative N balance:
- intake < output
- net loss of protein
- never normal
- caused by; trauma, infection or malnutrition
Describe the nitrogen balance in a 70kg male
What is protein turnover?
The continuous breakdown and resynthesis of protein.
- rate of turnover depends on:
- growth (increased rate)
- ageing (decreased rate)
- half-life of body protein in ~80 days
- total protein turnover = 300-400g/day
What are glucogenic amino acids and give two examples?
Amino acids that can be used to synthesise glucose or glycogen.
Examples:
- Aspartate
- Asparagine
- Alanine
- Glycine
- Cysteine
- Serine
- Arginine
- Proline
- Histidine
- Glutamine
- Glutatmate
- Methionine
- Valine
What are ketogenic amino acids and give two examples
Amino acids that can be used to synthesise fatty acids or ketone bodies.
Examples:
- Lysine
- Leucine
Which amino acids are both glucogenic and ketogenic? (2 examples)
- Threonine
- Tryptophan
- Tyrosine
- Phenylalanine
- Threonine
- Isoleucine
What are the 9 essential amino acids?
Body cannot produce ‘essential’ amino acids - they need to be sourced from our diet
If - Isoleucine
Learned - Lysine
This - Threonine
Huge -Histidine
List -Leucine
May - Methionine
Prove - Phenylalanine
Truly - Tryptophan
Valuable -Valine
What extra amino acids do children and pregnant women require?
They have a high rate of protein synthesis so also require arginine, tyrosine ad cysteine from the diet.
How are amino acids in the body synthesised?
- Carbohydrates from:
- glycolysis
- pentose phosphate pathway
- krebs cycle
- Amino group from other amino acids (transamination) or from ammonia
Which important compounds are synthesised from amino acids?
Why are amino groups removed from amino acids?
- removal of an amino group:
- exposes the carbon skeleton to be utilised in oxidative metabolism
- allows nitrogen to be used in other compounds
- allows nitrogen to be excreted in urea
How is nitrogen removed from amino acids?
Transamination
- aminotransferases use alpha ketoglutarate to funnel amino acid to glutamate
- exception = aspartate aminotranferases use oxaloacetate to funnel amino group to aspartate
- All aminotrasferases require coenzyme pyridoxal phosphate which is a derivative of vitamin B6
Deamination
- removes amino groups as free ammonia
- takes place in liver and kidneys
- ammonia needs to quickly be converted into urea
- enzymes that deaminate amino acids:
- amino acid oxidases
- glutaminase
- glutamate dehydrogenase
Which aminotransferases are key biomarkers?
Alanine aminotransferase (ALT)
- converts alanine to glutamate
Aspartate aminotransferase (AST)
- converts glutamate to aspartate
Plasma levels of AST and ALT are measured routinely as part of a liver function test:
- high levels when hepatocyte necrosis occurs
- viral hepatitis
- Autoimmune liver diseases
- Toxic injury
What is urea?
Non-toxic high nitrogen content molecule that is extremely water soluble. Mostly excreted in urine through the kidney where it also performs an osmotic role in the kidney tubules.
What is the urea cycle?
An inducible unregulated cycle that converts excess ammonia into urea using the mitochondria of liver cells.
- occurs in the liver and involves 5 enzymes
- enzymes are expressed in relation to the amount of ammonia needed tobe exposed
- high protein diet = induces enzyme levels
- low protein diet = represses levels
- enzymes are expressed in relation to the amount of ammonia needed tobe exposed
What is refeeding syndrome?
An increase in the ammonia toxicity due to refeeding severely malnourished pts as their urea cycle enzymes have been downregulated.
Risk factors:
- BMI <16kg/m2
- unintentional weight loss >15% in 3-6 months
- 10 days or more with little or no nutritional intake
How to refeed:
- 5 - 10 kcal/kg/day
- raise gradually to fulfil needs within a week
What are the defects of the urea cycle?
Autosomal recessive genetic disorders caused by deficiency of one of the enzymes in the urea cycle
- ~1 in 30,000 live births
- mutations can cause a partial loss of enzyme function causing:
- hyperammonaemia
- accumulation/excretion of urea cycle intermediates
Clinical picture:
- the severity of NH3 nature of defect and amount of protein eaten
- severe disorders are apparent within 1 day; child will die if untreated
- mild disorders may not be apparent until early childhood
Treatment:
- Low protein diet
- Replace amino acids with keto acids
What are the symptoms of urea cycle defects?
Symptoms:
- vomiting
- lethargy
- irritability
- mental retardation
- seizures
- coma
What is the biochemical basis of ammonia toxicity?
- readily diffusible and extremely toxic to brain
- blood level should be kept low (25-40umol/L)
- potential toxic effects
- disrupts cerebral blood flow
- interfere with a.a. transport, protein synthesis and TCA cycle
- increases pH
- disrupts the metabolism of glutamate and aspartate neurotransmitters
- alters blood-brain barrier
