Proteins And Amino Acid Metabolism + PKU + Homocystinuria Flashcards
Outline phenylketonuria
Deficiency in phenylalanine hydroxylase
- Causes an accumulation of phenylalanine as it cant be converted to tyrosine
- Phenylalanine becomes transaminated to phenylpyruatve
- Accumulation of phenylketones
Symptoms of PKU
Phenylketones in urine > musty smell
Severe intellectual disability
Developmental delay
Small head
Seizures
Hypopigmentation
Outline homocystinuria
Cannot breakdown methionine to cysteine
Defect in cystathionine B-synthase
Build up of homocysteine > excreted in urine
Treatment of homocystinuria
Low methionine diet
Less milk, meat, fish, cheese, eggs + nuts
Cysteine, vitamin B6, 12 and folate supplement
Supplements can be used to treat homocystinuria
What supplement and why?
Vitamin V6, B12 + folate
Homocysteine > methionine is promoted by them
Less accumulation of homocysteine
Treatment of PKU
Low phenylalanine diet
High tyrosine diet
Avoid artifical sweeteners
Avoid high protein foods - meat, milk + eggs
Homocystinuria and Marfan’s;s syndrome have some similar clinal feature
What are they?
How can you distinguish between the two?
Similar:
- skeletal deformities
- lens dislocation
Different
- homocystine levels high in homocystinurea but normal in Marfan’s
What is creatinine?
Breakdown product of creatine and creatine phosphate in muscles
What does creatinine a useful clinical marker of?
- Real function
- Estimates muscle mass - Creatinine urine excretion over 24h is proportional to muscle mass
What is an abnormal nitrogen balance?
negative N balance - Intake < output
Causes of a negative nitrogen balance
Trauma
Infection
Malnutrition
What are three major nitrogen containing compounds?
Amino acid
Proteins
Purine + pyrimidine
What is nitrogen balance?
Nitrogen input - nitrogen output
When is a positive nitrogen balance normal?
Growth
Pregnancy
Adult recovering from malnutrition
What is protein turnover?
Balance between protein synthesis and protein degradation
Example of a glucogenic amino acid
Alanine
Example of a ketogenic amino acid
Leucine
Example of both a glucogenic and ketogenic amino acid
Isoleucine
When does mobilisation of protein reserves occur?
Extreme stress - starvation
What are the 9 essential amino acids?
Isoleucine
Lysine
Threonine
Histidine
Leucine
Methionine
Phenylalanine
Tryptophan
Valine
If Learned This Huge List May Prove ** Truly Valuable
What amino acids can be conditionally essential and when?
-
Tyrosine - low in phenylalanine or phenylalanine hydroxylase deficient
-Cysteine - low in methionine - Arginine
Or in pregnancy and children
Where do carbon atoms for non-essential amino acid syntehsis come from?
Glycolysis intermediates
Pentose phosphate pathway
Kerbs cycle
What are the pathways which facilitate removal of nitrogen from amino acids?
Transamination
Deamination
Outline transamination
- Transfers amine group from one amino acid to another group e.g. keto acid
- require the coenzyme pyridoxal phosphate
What are the aminotransferases in the liver function test?
Alanine aminotransferase ALT
Aspartate aminotransferase AST
What does alanine aminotransferase do?
Catalyses alanine + a-ketoglutarate > pyruvate + glutamate
What does aspartate aminotransferase do?
Catalyses asparatate + a-ketoglutarate >oxaloacetate + glutamate
Outline deamination
- Liberates amino acid group as free ammonia
- in liver and kidneys
- NH3 > NH4+ at physiological pH
3 enzymes which deaminate amino acids
Amino acid oxidases
Glutaminase
Glutamate dehydrogenase
How is urea excreted?
In urine via kidneys
Management of urea cycle defects
Low protein diet
Replace amino acids in diet with keto acids
4 properties of urea
Non toxic
Water soluble
Chemically inert
High nitrogen content
Symptoms of urea cycle defects
Vomiting
Lethargy
Irritability
Mental retardation
Seizures
Coma
How many enzymes are involved in the urea cycle?
5
Outline potential toxic effects of ammonia toxicity
- disruption of cerebral blood flow
- ^pH
- alters blood brain barrier
- interference with TCA cycle
- interference with aa transport and protein synthesis
What are the two mechanisms to safely transport ammonia from tissues to liver?
Glutamine
Alanine
Outline the mechanism of glutamine in the safe transport of ammonia
- ammonia + glutamate > glutamine
- glutamine transported in blood to liver or kidneys
glutaminase - glutamine > ammonia + glutamate
- liver: ammonia put into urea cycle
- kidneys: excreted in urine
Outline the mechanism of alanine in the safe transport of ammonia
- transamination - amine group transferred to glutamate
- amine groups from glutamate > urea cycle
- pyruvate is transaminated by glutamate > alanine
- alanine is sent to liver
- alanine > pyruvate
- pyruvate > glycolysis
What is the heel prick test used to test?
- sickle cell disease
- cystic fibrosis
- congential hypothyroidism
- PKU
- homocystinuria
Cysteine vs cystine vs homocysteine vs homocystine
Cysteine - amino acid
Cystine - 2 x cysteine
Homocysteine - made from methionine
Homocystine - 2 x homocysteine
Outline the molecular basis of re feeding syndrome
- down regulations enzymes in urea cycle due to low protein intake
- sudden high protein take overwhelms enzymes
- ammonia toxicity occurs
What is a main property of a glucogenic vs ketogenic amino acid?
- glucogenic: Can be converted to glucose truth gluconeogenesis
- ketogenic: can be converted into acetyl coA
