Nitrogen Flashcards
What do amino acids and nucleotides contain that carbohydrates and fats don’t?
Nitrogen
Where do we get nitrogen from?
our diet
What does pepsin do?
cuts protein into peptides in the stomach
What do trypsin and chymotrypsin do?
cut proteins and larger peptides into smaller peptides in the small intestine
What do amino peptides and carboxy peptides A and B do?
degrade peptides into amino acids in the small intestine
What happens to dietary proteins?
They get enzymatically hydrolysed and broken down to eventually make AA
Primary role of carbs and fat?
to provide energy
Primary role of amino acids?
building blocks for proteins
What happens at the end of protein destruction?
produce individual AA
What enzyme converts phenylalanine to tyrosine?
Phenylalanine hydroxylase
What does phenylketonuria involve? (PKU)
absence/ deficiency of Phenylalanine hydroxylase
lots of phenylalanine building up and becomes other products such as Phenylpyruvate, Phenyllactate, Hydroxyphenylacetate and phenylacetate
spill over and appear in urine
Problem is that these products also cross the blood brain barrier, and cause irreversible damage to the developing brain
How does PKU manifest genetically?
two disease copies of brain, one from each parent
Clinical features of PKU?
Normal at birth with near normal blood Phe levels
Phe levels rise rapidly once feeding is established
Days 3-4 may present with irritability and feeding difficulties
If untreated, delayed mental development and neurological features are evident by 6 months of age
Musty odour
Neonatal screening program?
use of guthrie card
few spots of blood taken from blood sample
spotted onto circles
allowed to dry
Steps after PKU positive test?
Positive screening test
Quantitative amino acid analysis
Confirmation of increased blood Phe level
Typically decreased blood Tyrosine (Tyr) level
Presumptive diagnosis of PKU
Dietary treatment started immediately
Treatment of PKU?
Low protein diet supplemented with “protein” substitute
Maintain blood Phe levels between 120 – 360 umol/l
Blood Tyr maintained at upper limit of reference range
Monitor vitamin and trace element status
Managed by multi-disciplinary team
- Dietitians
- Metabolic physicians
- Biochemists
- Genetic counselling
Purpose of urea cycle?
To prevent too high a levels of ammonia in body
How to tell where a enzyme is non functional?
lots of metabolites at part before problem
Treatment of metabolic diseases?
enzyme replacement therapy
medicine to take product away and stop toxicity
What is most common inherited metabolic disorder from urea cycle defects?
Most common is ornithine transcarbamoylase (OTC) deficiency
Incidence of 1 in 40,000 births in UK
What are urea cycle defects?
group of inherited metabolic disorders
six enzymes to six inherited disorders
What is the inheritance type of OTC?
OTC has X-linked inheritance, rest are autosomal recessive
Symptoms of OTC?
Characterised by hyperammonaemia (elevated blood ammonia level) – highly toxic
Elevated blood ammonia is a medical emergency
Typically presents in newborn period
How severe is hyperammenia?
medical emergency
highly toxic
rapidly cause damage to brain
How do we solve blockages in the urea cycle?
sodium benzoate and glycine conjugate to form non toxic product
excretes through urine
sodium phenylbutyrate and phenylacetate, phenylacetate takes glucose and forms phenylacetylglutamine
excretes through urine
also dialyse ammonia
