2. Protein And Amino Acid Metabolism Flashcards
What are the major and minor nitrogen containing compounds?
Major: amino acids, proteins, purines and pyrimidines
Minor: porphyrins, creatine phosphate, neurotransmitters
What is creatinine?
Breakdown product of creatine and creatine phosphate
Produced at constant rate depending on muscle mass
Provides estimate of muscle mass - creatinine urine excretion over 24h proportional to muscle mass
What is N equilibrium?
Intake = output
No change in total body protein
Normal state in adult
What is positive N balance?
Intake > output
Increase in total body protein
Normal state in growth and pregnancy or in adult recovering from malnutrition
What is negative N balance?
Intake < output
Net loss of body protein
Never normal
Causes include trauma, infection or malnutrition
Name a glycogenic amino acid and a ketogenic amino acid
Glucogenic - alanine
Ketogenic - lysine
Name an amino acid that is both glucogenic and ketogenic
Tyrosine
What happens in Cushing’s syndrome?
Excessive breakdown of protein fur to excess cortisol
Weakens skin structure leading to striae formation (stretch marks)
What extra amino acids do children and oregano women require in their diet?
Arginine
Tyrosine
Cysteine
Where do carbon atoms for non-essential amino acid synthesis come from?
Intermediates of glycolysis
Pentose phosphate pathway
Krebs cycle
Why is removal of amino group from amino acid essential?
To allow carbon skeleton of amino acids to be until I see in oxidative metabolism
What are the 2 main pathways that facilitate removal of nitrogen form amino acids?
Transamination
Deamination
What is transamination?
amino acid 1 + keto acid 2 amino acid 2 + keto acid 1
Transfer of the amine group of an amino acid with the oxygen of a keto acid
Most amino acids are converted to glutamate and some to aspartate
What do most aminotransferase enzymes use?
What is the exception?
Alpha-ketoglutarate to funnel amino group to glutamate
Exception: aspartate aminotransferase uses oxaloacetate to funnel amino group to aspartate
What do all aminotransferase require?
Coenzyme pyridoxal phosphate which is a derivative of vitamin B6
What are ALt and AST and what do they do?
ALT - alanine aminotransferase, converts alanine to glutamate
AST - aspartate aminotransferase, converts glutamate to aspartate
What can plasma ALR and AST levels show?
Measures as part of liver function test
Levels particularly high in conditions that cause extensive cellular necrosis such as: viral hepatitis, autoimmune liver disease, toxic injury
What is deamination?
Liberates amino group as free ammonia
Mainly occurs in liver and kidney
Also important in deamination of dietary D-amino acids
Name the enzymes that can deamination amino acids
Amino acid oxidases
Glutaminase
Glutamate dehydrogenase
Describe features of the urea cycle
Occurs in liver
Involves 5 enzymes
Amount of urea cycle enzymes relate to need to dispose of ammonia
High protein diet induce enzyme levels
Low protein diet or starvation represses levels
What is refeeding syndrome?
Can occur when nutritional support given to severely malnourished patients
Ammonia toxicity significant factor
What defects can occur in the urea cycle?
Autosomal recessive geneticist disorders caused by deficiency of one of enzymes in urea cycle
Mutations cause a atrial loss of enzyme function
What can defects in the urea cycle lead to?
Hyperammonaemia
Accumulation/excretion of urea cycle intermediates
When do severe urea cycle disorders present?
Show symptoms within 1 day after birth, can lead to death if left untreated
What is the management of a patient with a defect in the urea cycle?
Low protein diet
Replace amino acids in diet with keto acids
What are the 2 mechanisms utilised for the safe transport of amino acid nitrogen from tissues to the liver for disposal?
Using glutamine and using alanine
What is glutamine transport?
Ammonia combined with glutamate to form glutamine
Glutamine transported in blood to liver or kidneys, it’s cleaved by glutaminase to reform glutamate and ammonia
In liver, ammonia fed into urea cycle
What is alanine transport?
Amine groups transferred to glutamate by transamination
Pyruvate transaminated by glutamate to form alanine
Alanine transported in blood to liver, converted back to pyruvate by transamination
Amino group fed via glutamate into urea cycle
What inborn errors of metabolism can be detected with the heel prick test?
Phenylketonuria Maple syrup urine disease Isovaleric acidaemia Glutaric aciduria Homocystinuria
What is phenylketonuria?
Deficiency in phenylalanine hydroxylase
Autosomal recessive
Accumulation of phenylalanine in tissue, plasma and urine
Phenylketones in urine
What is the treatment for phenylketonuria?
Low phenylalanine diet etched with tyrosine
Avoid high protein foods such as meat, milk and eggs
What are the symptoms of phenylketonuria?
Sever intellectual disability
Developmental delay
Microcephaly
Seizures
What is homocystinuria?
Problem breaking down methionine Excess homocystine excreted in urine Autosomal recessive Defect in cystathionine beta-synthase Affects connective tissue, muscles, CNS and CVS
What is the treatment for homocystinuria?
Low-methionine diet
Avoid milk, meat, fish, cheese, eggs
Cysteine, vit B6, beanie, B12 and folate supplement
What is elevated plasma homocysteine shown to be associated with?
Cardiovascular disease
