Flashcards in 9. Protein and Amino Acid Metabolism Deck (43):
What is creatinine the breakdown product of?
Creatine and Creatine phosphate in the muscle.
How is creatinine link to muscle mass.
The amount excreted is proportional to muscle mass so provides an estimate of muscle mass.
What can creatinine be used as a clinical marker for?
Muscle mass and kidney function.
What contributes to intake of nitrogen?
What contributes to the output of nitrogen?
Loss of skin, hair, nail and N-waste product in faeces and urine.
Where is nitrogen stored in the body?
Amino acid pool and N-containing compounds.
What is N equilibrium and what are the implications on body protein and health?
Where input= output. No change in body protein and normal healthy state in adults.
What is positive N balance and what are the implications on body protein and health?
Intake > output. There's an increase in body protein, there is normal health in growth and pregnancy or in adults recovering from malnutrition.
What is negative N balance and what are the implications on body protein and health?
What are the three routes an amino acid can go down to produce energy?
Glucogenic, ketogenic or both glucogenic and ketogenic.
What is one example of a glucogenic amino acid?
Alanine, glycine, cysteine, serine, arginine, proline, histidine, glutamine, glutamate, methionine, valine, aspartate, asparagine.
What is one example of a ketogenic amino acid?
Lysine or leucine.
What is an example of a glucogenic/ketogenic amino acid?
Treonine, tryptophan, tyrosine, phenyalanine or isoleucine.
When are protein reserves metabolised?
Under extreme stress, starvation.
How is protein reserve metabolism regulated?
By hormonal control. Insulin and growth hormone decrease protein degradation but glucocorticoids increase protein degradation.
What can excessive breakdown of protein occur in?
Cushing's syndrome, can lead to striae formation.
What are the nine essential amino acids?
Why is it essential that vegetarian diets have a wide variety of plant sources?
Because, unlike meat, proteins of plant origin are deficient in at least one essential amino acid so to obtain all essential amino acids, there must be a variety of plant proteins eaten.
Where do carbon atoms for non-essential amino acid synthesis come from?
Intermediates of glycolysis, pentose phosphate pathway or Kreb's cycle.
What two main pathways facilitate removal of nitrogen from amino acids?
Transamination and deamination.
What happens in transamination?
The R group from an amino acid and a keto acid swap over. Normally a-ketoglutarate is used to funnel the amino group to glutamate. But aspartate amino transferase uses oxaloacetate to funnel amino group to aspartate. The coenzyme pyridoxal phosphate is required.
What are two key aminotransferase enzymes?
Alanine aminotransferase (converts alanine to glutamate) and aspartate aminotransferase (converts glutamate to aspartate).
What happens in deamination?
The amino acid group is released as free ammonia, mainly happens in the liver and kidney.
What happens to the ammonia produced in deamination?
It is converted to urea or excreted directly in urine.
What enzymes can deaminate amino acids?
Amino acid oxidases, glutaminase and glutamate dehydrogenase.
What are some factors of urea?
High nitrogen content, non-toxic, water soluble, chemically inert in humans, excreted in urine and has an osmotic role in kidney tubules.
Where does the urea cycle take place?
In the liver.
How is the urea cycle controlled?
By the amount of substrate available. High protein induces enzyme levels, low protein represses levels. The cycle is induced, not regulated.
Why must refeeding be done gradually?
Because sudden high levels will lead to ammonia toxicity as the urea cycle won't be up regulated quickly enough.
What can defects in the urea cycle lead to?
Hyperammonaemia or accumulation/excretion of urea cycle intermediates.
What does the severity of defects in the urea cycle depend on?
The nature of the defect and the amounts of protein consumed.
How are defects in the urea cycle managed?
By a low protein diet and replacing amino acids with keto acids.
What are some symptoms of defects in the urea cycle?
Vomiting, lethargy, irritability, mental retardation, seizures and coma.
Why is ammonia toxicity a problem?
Ammonia is readily diffusible across the blood brain barrier. It can lead to potentially toxic side effects, such as: interference with amino acid transport and protein synthesis, disruption of cerebral blood flow, pH becomes more alkaline, metabolism of excitatory amino acid neurotransmitters is interfered with, alternation of the blood-brain barrier and interference of the TCA cycle.
Briefly explain the two mechanisms for safe transport of ammonia from the tissues for disposal.
1) Glutamine. Ammonia combines with glutamate to from glutamine, Glutamine is transported to the liver or kidneys and us cleaved glutaminase to reform glutamate and ammonia, the ammonia is fed into the urea cycle in the liver or excreted directly in urine from the kidneys.
2) Alanine. alanine is formed by transamination of pyruvate million it's transported in the blood to the liver and is converted back to pyruvate by transamination, the amino group is fed into the urea cycle for disposal as urea and pyruvate is used to synthesise glucose to be fed back into tissues.
How are amino acid metabolism problems screened for?
Using the heel prick test.
How are defects of amino acid metabolism managed?
By restricting the specific amino acids in diet.
Explain the most common inborn error amino acid metabolism.
Phenylketonuria (PKU). It's caused by a deficiency in phenylalanine hydroxylase. It's an autosomal recessive genetic abnormality. It causes accumulation of phenylalanine in the tissue, plasma and urine.
How is phenylketonuria treated?
Having a low phenylalanine diet, avoid artificial sweeteners, avoid high protein foods.
What are the symptoms of phenylketonuria?
Intellectual disability, developmental delay, microcephaly (small head), seizures and hypopigmentation.
What is homocystinurias?
Problems metabolising methionine, leading to excess homocysteine excreted in urine, it's an autosomal recessive disorder commonly caused by a defect in cystathionine B-synthase.
How are homocystinurias treated?
Low methionine diet, avoid milk, meat, fish, cheese, eggs, and use cysteine, vitamin B6, betting, B12 and folate supplements.