Protein & amino acid metabolism Flashcards
(21 cards)
Describe the pathway of protein turnover
Proteins are broken down into free amino acids. They can then either be used to synthesise cellular proteins or be sent to the liver.
When at the liver they are split into either the amino group or carbon skeleton.
The amino group is then excreted via the urea/urine pathway.
The carbon skeleton is either glucose in or ketogenic. Glucogenic will undergo gluconeogensis and ketogenic amino acids will form ketone bodies. These can both provide energy.
Give an example of a glucogenic and ketogenic amino and an example of one that is both.
Glucogenic- e.g. aspartate and asparagine.
Ketogenic - lysine or leucine only 2
Both - tryptophan and threonine
Explain how and why protein mobilisation occurs
This occurs during extreme starvation.
It is controlled completely by hormones.
Insulin and growth hormone increase the effect on protein synthesis and decrease the effect on protein degradation.
Glucocorticoids are the other way round.
What disease causes an excessive breakdown of proteins?
Cushing disease - excess cortisol
It weakens structure of skin and leads to striae formation and centralised obesity.
What is a peptide bond?
The bond between two amino acids - the OH part of the carboxyl group is removed and the H on the other amino group is removed so the 2 carboxyl/amino groups join. Water is a by product of this reaction.
Where do the carbons for non essential amino acid synthesis come from?
Intermediates of glycolysis
Pentose phosphate pathway
Krebs cycle
Where does the amino group come from in the in vivo synthesis of amino acids?
Provided by other amino acids via transamination or from ammonia
Give 2 examples of amino acids specially needed for the synthesis of important compounds
Histidine - histamine
Typtophan - serotonin and melatonin
What is transamination?
Where the amine group is transferred over to make a new amino acid. They are combined with a keto acid which also produces another keto acid during the process. This is catalysed by an amino transferase.
What is transamination?
Where the amine group is transferred over to make a new amino acid. They are combined with a keto acid which also produces another keto acid during the process. This is catalysed by an amino transferase.
What is the co-enzyme that all aminotransferases require and where does it come from?
Coenzyme pyridoxal phosphate and it is a derivative of vitamin B6
What are 2 key aminotransferases and what do they do?
Alanine aminotransferase- catalyses the inter conversion of alanine and a-ketoglutarate to pyruvate and glutamate
Asparatate aminotransferase - catalyses the intercom version of aspartate and a-ketoglutarate to oxaloacetate and glutamate
Levels particularly high in. Risk hepatitis, autoimmune liver disease and toxic injuries e.g. death cap mushroom ingestion.
What is deamination?
This frees the amino group as free amino. Occurs mainly in liver and kidneys. The keto acids can be used for energy but the ammonia must be excreted, converted to urea then urine.
Enzymes that can de-aminate amino acids include amino acid oxidases, glutamine’s and glutamate dehydrogenase.
What are symptoms associated with defects in the urea cycle?
Dependent on nature of defect and amount of protein eaten. Including lethargy, vomiting, irritability, intellectual disability, seizures and coma.
How do you manage a urea cycle defect?
A low protein diet and also replace amino acids in diet with keto acids.
Explain ammonia toxicity effects
Disrupts cerebral blood flow, makes the blood alkali. Alteration of BBB, interferes with TCA cycle. Interference with metabolism of neurotransmitters e.g. GABA.
How is amino acid nitrogen safely transported from the tissues to the liver for disposal?
- Glutamine - ammonia combines with glutamate to form glutamine. Then transported in blood to liver or kidneys where it’s cleaved by glutamine to reform glutamate and ammonia. In liver, ammonia directly enters into urea cycle. In kidneys directly excreted as urine.
- Alanine - amine group transferred to glutamate by transamination. Pyruvate then transamination by glutamate to form alanine. Alanine taken to liver and converted back to pyruvate by transamination. Then amino group fed into urea cycle via glutamate for disposal as urea. Pyruvate is used to synthesised glucose so gets fed back into the tissues.
What are some things that they heel prick test screen for?
Sickle cell disease
Cystic fibrosis
Congenital hypothyroidism
Phenylketonuria
Homocystinuria
Maple syrup urine disease
Describe the disease phenylketonuria e.g. causes, symptoms, treatment
Deficiency in phenylalanine hydroxylase. Autosomal recessive gene on chromosome 12.
Phenylalanine can’t be broken down into tyrosine by phenylalanine hydroxylase.
Phenylalanine gets transaminated to phenylpyruvate then Broken down into phenylketones which then Accumulate and are excreted via urine.
Symptoms- severe intellectual disability, developmental delay, microcephaly, seizures, hypopigmentation.
Treatment - low phenylalanine diet enriched with tyrosine. Avoid artificial sweeteners and high protein foods.
What pathways can be affected due to a lack of tyrosine from the phenylketonuria disease?
Noradrenaline and adrenaline
Dopamine
Melanin
Thyroid hormones
General protein synthesis
What is homocystinuria?
Protein methionine converted to homocysteine.
Normally would be converted to cyststhionine and then cysteine but a defect in cystathionine B-synthase means homocysteine builds up.
This enzyme also requires vit B6 as a cofactor.
Treatment: low methionine diet, avoid high protein foods and nuts which content methionine. Need cysteine and vitamin B 6&12 supplementation.
